Unnamed: 0
int64 0
2.34M
| title
stringlengths 5
21.5M
| abst
stringlengths 1
21.5M
|
|---|---|---|
2,334,900 |
A Comparative Study of Three Vasopressors for Maintenance of Blood Pressure during Spinal Anesthesia in Lower Abdominal Surgeries.
|
Subarachnoid block, although being highly efficient with lesser drug doses, often has limitation such as hypotension, continues to be a matter of concern to the anesthetist. The present study was aimed to compare the use of phenylephrine, ephedrine, and mephentermine bolus for maintenance of blood pressure during spinal anesthesia in lower abdominal surgeries.</AbstractText>In a randomized, prospective study, 90 adult patients of either sex who developed hypotension during surgery under subarachnoid block were allocated into three groups to receive bolus phenylephrine, ephedrine, and mephentermine. The number of boluses and time taken to recover from hypotension was noted. Occurrence of adverse effects in the perioperative and postoperative period was also noted.</AbstractText>Results were analyzed by Student's paired t</i>-test and Chi-square test. The ANOVA test was used to compare the group variances among the study groups. P</i> < 0.05 was considered statistically significant. Thirty-four hypotensive events (average 1.03 events/patient) took place in mephentermine group. In phenylephrine group, a total of 53 hypotensive events took place. On an average, the group had a total of 1.61 hypotensive events per patient. No hypotensive event took place in ephedrine group after the first bolus of drug (average 1 event/patient). Mean heart rate in phenylephrine group was significantly lower as compared to the other two groups (P</i> < 0.001).</AbstractText>Mephentermine and ephedrine were similar in performance, offered a better hypotensive control, and had lower recurring events as compared to phenylephrine.</AbstractText>
|
2,334,901 |
Are cardiovascular risk parameters and glycemic levels associated with periodontitis in type 2 diabetes patients? A clinical study.
|
This study investigated the associations between cardiovascular risk parameters, glycemic level and periodontitis in the diabetic adult population. BMI (body mass index), total cholesterol and triglyceride was used as cardiovascular risk measure and glycosylated hemoglobin (HbA1c) was recorded for glycemic levels. Study results provide evidence of significant association between periodontal disease, cardiovascular risk and glycemic levels.
|
2,334,902 |
SGLT2 inhibition and kidney protection.
|
Type 2 diabetes mellitus (T2DM) is a growing public health concern worldwide. Numerous drug classes are available for treatment, however, their efficacy with regard to diabetes-induced renal and cardiovascular (CV) complications remains limited. Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) are a new class of blood glucose lowering medications that block renal glucose reabsorption and have protective effects on the kidney and the heart. This review focusses on the effects of SGLT2 inhibitors on the kidney and renal outcome: it briefly outlines renal glucose handling in diabetes and its role in glomerular hyperfiltration and renal hypoxia; describes how SGLT2 inhibitors induce an early, reversible reduction in glomerular filtration rate (GFR) and preserve GFR in the long-term in patients with T2DM; discusses whether the enhanced active transport in the renal outer medulla (OM) in response to SGLT2 inhibition is friend or foe; proposes how the blood pressure lowering and heart failure protective effect of SGLT2 inhibitors can be preserved in chronic kidney disease (CKD) despite attenuated antihyperglycemic effects; and examines whether SGLT2 inhibition enhances the incidence or severity of acute kidney injury (AKI).
|
2,334,903 |
Effect of Prenatal Laterality Disturbance and Its Accompanying Anomalies on Survival.
|
In this retrospective, observational study of fetuses diagnosed with a laterality disturbance we describe the findings and outcome of fetuses diagnosed between 1980 and 2017 at a tertiary fetal-pediatric cardiology unit. In addition we sought to identify features which impact on outcome. Left atrial isomerism (LAI) was diagnosed in 177 babies and right atrial isomerism (RAI) in 100. Major structural heart disease was present in all cases of RAI and 91% with LAI. Complete heart block (CHB) was present in 40% of LAI. For surviving live-born infants a biventricular circulation was feasible in 3% with RAI and 43% with LAI. The median survival for live-borns with LAI was 13 months (range 0 to 272 months) and for RAI 19 months (range 0.3 to 292 months). The median postnatal survival with CHB was 0.2 months (range 0 to 228 months) compared to 44 months with sinus rhythm (interquartile range 0 to 272 months; p <0.0001). The 5-year survival was 1980 to 1989, RAI 0%, LAI 0%; 1990 to 1999, RAI 62%, LAI 54%; 2000 to 2009, RAI 59%, LAI 53%; 2010 to 2017, RAI 67%, LAI 75% by era. The rate of intrauterine death remained. Risk factors for death/transplantation for RAI were total anomalous pulmonary venous drainage, left heart obstruction (hazard ratios 2.7, p = 0.048; 5.8, p = 0.03) and for LAI: CHB, anomalous pulmonary venous drainage and right heart obstruction (hazard ratios 11.5, 6.2, 3.8, respectively (p = 0.008, p = 0.003, p <0.001)). In conclusion, laterality disturbances represent a complex form of congenital heart disease and although survival is improved, it remains poor especially in the presence of anomalous pulmonary venous drainage, stenotic and/or atretic valves, and CHB.
|
2,334,904 |
Systematic Review of Biofeedback Interventions for Addressing Anxiety and Depression in Children and Adolescents with Long-Term Physical Conditions.
|
Children and adolescents with long-term physical conditions are at increased risk of psychological problems, particularly anxiety and depression, and they have limited access to evidence-based treatment for these issues. Biofeedback interventions may be useful for treating symptoms of both psychological and physical conditions. A systematic review of studies of biofeedback interventions that addressed anxiety or depression in this population was undertaken via MEDLINE, EMBASE, PsycINFO, CINAHL and the Cochrane Central Register of Controlled Trials databases. Primary outcomes included changes in anxiety and depression symptoms and 'caseness'. Secondary outcomes included changes in symptoms of the associated physical condition and acceptability of the biofeedback intervention. Of 1876 identified citations, 9 studies (4 RCTs, 5 non-RCTs; of which all measured changes in anxiety and 3 of which measured changes in depression) were included in the final analysis and involved participants aged 8-25 years with a range of long-term physical conditions. Due to the heterogeneity of study design and reporting, risk of bias was judged as unclear for all studies and meta-analysis of findings was not undertaken. Within the identified sample, multiple modalities of biofeedback including heart rate variability (HRV), biofeedback assisted relaxation therapy and electroencephalography were found to be effective in reducing symptoms of anxiety. HRV was also found to be effective in reducing symptoms of depression in two studies. A range of modalities was effective in improving symptoms of long-term physical conditions. Two studies that assessed acceptability provided generally positive feedback. There is currently limited evidence to support the use of biofeedback interventions for addressing anxiety and depression in children and adolescents with long-term physical conditions. Although promising, further research using more stringent methodology and reporting is required before biofeedback interventions can be recommended for clinical use instead or in addition to existing evidence-based modalities of treatment.
|
2,334,905 |
Short-term postoperative complications and prognostic factors in patients with adenocarcinoma of the esophagogastric junction.
|
The study was conducted to investigate the short-term complications and prognostic factors in patients with esophagogastric junction adenocarcinoma (EGJA).</AbstractText>This retrospective study included 110 EGJA patients who underwent surgery from January 2010 to November 2012 at The First Affiliated Hospital of BengBu Medical College. The overall survival and short-term complications were analyzed according to the patients' clinical characteristics.</AbstractText>The incidence of postoperative cardiopulmonary complications was significantly higher in patients with preoperative cardiopulmonary disease or elderly patients (P < 0.05). Four cases of upper margin cancer residue were detected using the abdominal approach and three using the thoracic approach, which indicated that the cancer residue margin was related to surgical approach. The overall five-year survival rate was 34.3% and statistically differed according to pathological stage and en block resection (Pall</sub> < 0.05). Cox regression analysis showed that lymph node metastasis (P < 0.05) and the extent of tumor invasion (P < 0.05) were independent prognostic factors.</AbstractText>Elderly patients with preoperative cardiopulmonary disease had an increased risk of developing postoperative cardiopulmonary complications. Lymph node status and depth of tumor invasion were independent factors related to patient prognosis.</AbstractText>© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.</CopyrightInformation>
|
2,334,906 |
Continuous femoral nerve block and patient-controlled intravenous postoperative analgesia on Th1/Th2 in patients undergoing total knee arthroplasty.
|
The purpose of this study is to observe and compare the effects of continuous femoral nerve block (cFNB) and patient-controlled intravenous analgesia (PCIA) on postoperative analgesia and Th1/Th2 in patients undergoing total knee arthroplasty (TKA). Forty-six TKA were selected and randomly divided into two groups: the cFNB group and PCIA group. Patients in the two groups all underwent general anesthesia using a laryngeal mask. In the cFNB group, the femoral nerve block and catheterization were performed after induction of general anesthesia: 0.375% ropivacaine hydrochloride with a 20 mL loading dose was provided. After the end of the operation, the electronically controlled analgesia pump was connected. In the PCIA group, fentanyl with a 0.05 mg loading dose was provided and the electronic controlled analgesia pump was connected at the end of the operation. Venous blood was collected before anesthesia (T0), 1 h postoperatively (T1), 24 h postoperatively (T2) and 48 h postoperatively (T3). Th1/Th2 was calculated and analyzed by flow cytometry, and other indexes of these time points were recorded. The results show that there was no significant difference between the two groups regarding changes in blood pressure, heart rate and postoperative sedation Ramsay score. There was no significant difference in Th1 percentages (Th1%), Th2 percentages (Th2%) and ratios of Th1-to-Th2 (Th1/Th2) between the two groups at T0, T1 and T2 (P>0.05), while the Th1%, Th2% and Th1/Th2 of the PCIA group were lower than those of the cFNB group at T3 (P less than 0.05). It was concluded that cFNB represents a better postoperative analgesia for patients than PCIA, and has a lesser effect on Th1/Th2 balance, which can improve the outcome of patients.
|
2,334,907 |
Neuromuscular Adaptations Following Training and Protein Supplementation in a Group of Trained Weightlifters.
|
The purpose of this study was to examine the effects of a recovery supplement compared with a placebo on muscle morphology in trained weightlifters. Vastus lateralis and muscle fiber cross sectional area of type I and type II fibers were compared between groups using a series of 2 &times; 2 (group &times; time) repeated measure ANOVAs. Both groups on average improved cross-sectional area of the vastus lateralis, type I and type II muscle fibers from pre-to-post but individual response varied within both groups. Greater magnitude of changes in type I and type II muscle fibers were observed for the placebo group but not for vastus lateralis cross sectional area. Additionally, subjects were divided into large and small fiber groups based on combined fiber size at the start of the investigation. These findings indicate that the recovery supplement utilized provided no greater effect compared with a placebo in a 12-week block periodization protocol in trained weightlifters. The primary determinate of fiber size changes in the study was determined to be the initial fiber size of muscle fibers with larger practical changes observed in the small fiber group compared with the large fiber group in type I, II, and ultrasound cross-sectional area (CSA).
|
2,334,908 |
A computational model of excitation and contraction in uterine myocytes from the pregnant rat.
|
Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials - from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes - that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes.
|
2,334,909 |
Longitudinal Associations of Neighborhood Crime and Perceived Safety With Blood Pressure: The Multi-Ethnic Study of Atherosclerosis (MESA).
|
High neighborhood crime and low perceptions of safety may influence blood pressure (BP) through chronic stress. Few studies have examined these associations using longitudinal data.</AbstractText>We used longitudinal data from 528 participants of the Multi-Ethnic Study of Atherosclerosis (aged 45-84, nonhypertensive at baseline) who lived in Chicago, Illinois. We examined associations of changes in individual-level perceived safety, aggregated neighborhood-level perceived safety, and past-year rates of police-recorded crime in a 1, ½, or ¼ mile buffer per 1,000 population with changes in systolic and diastolic BPs using fixed-effects linear regression. BP was measured five times between 2000 and 2012 and was adjusted for antihypertensive medication use (+10 mm Hg added to systolic and +5 mm Hg added to diastolic BP for participants on medication). Models were adjusted for time-varying sociodemographic and health-related characteristics and neighborhood socioeconomic status. We assessed differences by sex.</AbstractText>A standard deviation increase in individual-level perceived safety was associated with a 1.54 mm Hg reduction in systolic BP overall (95% confidence interval [CI]: 0.25, 2.83), and with a 1.24 mm Hg reduction in diastolic BP among women only (95% CI: 0.37, 2.12) in adjusted models. Increased neighborhood-level safety was not associated with BP change. An increase in police-recorded crime was associated with a reduction in systolic and diastolic BPs among women only, but results were sensitive to neighborhood buffer size.</AbstractText>Results suggest individual perception of neighborhood safety may be particularly salient for systolic BP reduction relative to more objective neighborhood exposures.</AbstractText>
|
2,334,910 |
Acute depletion of diacylglycerol from the <i>cis</i>-Golgi affects localized nuclear envelope morphology during mitosis.
|
Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis is a highly regulated process, but the detailed mechanism still remains incompletely understood. Previous studies have found that isolated diacylglycerol (DAG)-containing vesicles are essential for completing the fusion of the NE in nonsomatic cells. We investigated the impact of DAG depletion from the <i>cis</i>-Golgi in mammalian cells on NE reassembly. Using advanced electron microscopy, we observed an enriched DAG population of vesicles at the vicinity of the NE gaps of telophase mammalian cells. We applied a mini singlet oxygen generator-C1-domain tag that localized DAG-enriched vesicles at the perinuclear region, which suggested the existence of NE fusogenic vesicles. We quantified the impact of Golgi-DAG depletion by measuring the in situ NE rim curvature of the reforming NE. The rim curvature in these cells was significantly reduced compared with controls, which indicated a localized defect in NE morphology. Our novel results demonstrate the significance of the role of DAG from the <i>cis</i>-Golgi for the regulation of NE assembly.
|
2,334,911 |
Childhood Respiratory Risk Factor Profiles and Middle-Age Lung Function: A Prospective Cohort Study from the First to Sixth Decade.
|
Childhood risk factors for long-term lung health often coexist and their specific patterns may affect subsequent lung function differently.</AbstractText>To identify childhood risk factor profiles and their influence on lung function and chronic obstructive pulmonary disease (COPD) in middle age, and potential pathways.</AbstractText>Profiles of 11 childhood respiratory risk factors, documented at age 7, were identified in 8,352 participants from the Tasmanian Longitudinal Health Study using latent class analysis. We investigated associations between risk profiles and post-bronchodilator lung function and COPD at age 53, mediation by childhood lung function and adult asthma, and interaction with personal smoking.</AbstractText>Six risk profiles were identified: 1) unexposed or least exposed (49%); 2) parental smoking (21.5%); 3) allergy (10%); 4) frequent asthma, bronchitis (8.7%); 5) infrequent asthma, bronchitis (8.3%); and 6) frequent asthma, bronchitis, allergy (2.6%). Profile 6 was most strongly associated with lower forced expiratory volume in 1 second (FEV1</sub>) (-261; 95% confidence interval, -373 to -148 ml); lower FEV1</sub>/forced vital capacity (FVC) (-3.4; -4.8 to -1.9%) and increased COPD risk (odds ratio, 4.9; 2.1 to 11.0) at age 53. The effect of profile 6 on COPD was largely mediated by adult active asthma (62.5%) and reduced childhood lung function (26.5%). Profiles 2 and 4 had smaller adverse effects than profile 6. Notably, the effects of profiles 2 and 6 were synergistically stronger for smokers.</AbstractText>Profiles of childhood respiratory risk factors predict middle-age lung function levels and COPD risk. Specifically, children with frequent asthma attacks and allergies, especially if they also become adult smokers, are the most vulnerable group. Targeting active asthma in adulthood (i.e., a dominant mediator) and smoking (i.e., an effect modifier) may block causal pathways and lessen the effect of such established early-life exposures.</AbstractText>
|
2,334,912 |
A Novel Thermal Bubble Valve Integrated Nanofluidic Preconcentrator for Highly Sensitive Biomarker Detection.
|
In this study, we developed a new immunosensor that can achieve an ultralow detection limit and high sensitivity. This new device has an electrokinetic trapping (EKT)-based nanofluidic preconcentrator, which was integrated with oscillating bubble valves, to trap concentrated antigen and immunobeads. During the immunoassay process, oscillating bubbles rapidly grew and acted as control valves and to block the microchannel. Thereafter, the trapped preconcentrated antigen plug and antibody-coated nanobeads were preserved in the region between these two valves. Finally, the antigen concentration was quantitatively analyzed by a real-time measurement of Brownian diffusion of the immunobeads. In this work, the test sample used was C-reactive protein (CRP) which is a risk indicator of coronary heart disease and atherosclerosis.
|
2,334,913 |
Automatic classification of radiological reports for clinical care.
|
Radiological reporting generates a large amount of free-text clinical narratives, a potentially valuable source of information for improving clinical care and supporting research. The use of automatic techniques to analyze such reports is necessary to make their content effectively available to radiologists in an aggregated form. In this paper we focus on the classification of chest computed tomography reports according to a classification schema proposed for this task by radiologists of the Italian hospital ASST Spedali Civili di Brescia. The proposed system is built exploiting a training data set containing reports annotated by radiologists. Each report is classified according to the schema developed by radiologists and textual evidences are marked in the report. The annotations are then used to train different machine learning based classifiers. We present in this paper a method based on a cascade of classifiers which make use of a set of syntactic and semantic features. The resulting system is a novel hierarchical classification system for the given task, that we have experimentally evaluated.
|
2,334,914 |
AGE-RAGE axis blockade in diabetic nephropathy: Current status and future directions.
|
Diabetic nephropathy is one of the most frequent micro-vascular complications both in type 1 and type 2 diabetic patients and is the leading cause of end-stage renal disease worldwide. Although disparate mechanisms give rise to the development of diabetic nephropathy, prevailing evidence accentuates that hyperglycemia-associated generation of advanced glycation end products (AGEs) plays a central role in the disease pathophysiology. Engagement of the receptor for AGE (RAGE) with its ligands provokes oxidative stress and chronic inflammation in renal tissues, ending up with losses in kidney function. Moreover, RAGE activation evokes the activation of different intracellular signaling pathways like PI3K/Akt, MAPK/ERK, and NF-κB; and therefore, its blockade seems to be an attractive therapeutic target in these group of patients. By recognizing the contribution of AGE-RAGE axis to the pathogenesis of diabetic nephropathy, agents that block AGEs formation have been at the heart of investigations for several years, yielding encouraging improvements in experimental models of diabetic nephropathy. Even so, recent studies have evaluated the effects of specific RAGE inhibition with FPS-ZM1 and RAGE-aptamers as novel therapeutic strategies. Despite all these promising outcomes in experimental models of diabetic nephropathy, no thorough clinical trial have ever examined the end results of AGE-RAGE axis blockade in patients of diabetic nephropathy. As most of the AGE lowering or RAGE inhibiting compounds have emerged to be non-toxic, devising novel clinical trials appears to be inevitable. Here, the current potential treatment options for diabetic nephropathy by AGE-RAGE inhibitory modalities have been reviewed.
|
2,334,915 |
Citrulline Improves Early Post-Ischemic Recovery or Rat Hearts In Vitro by Shifting Arginine Metabolism From Polyamine to Nitric Oxide Formation.
|
Reperfusion or reopening of occluded vessels is the gold standard to terminate ischemia. However, early functional recovery after reperfusion is often low requiring inotropic intervention. Although catecholamines increase inotropy and chronotropy, they are not the best choice because they increase myocardial oxygen and substrate demand. As nitric oxide (NO) contributes to cardiac function, we tested the hypothesis that addition of citrulline during the onset of reperfusion improves post-ischemic recovery because citrulline can reenter arginine consumption of NO synthases (NOS) but not of arginases.</AbstractText>Hearts from adult rats were used in this study, exposed to 45-minute global ischemia and subsequently reperfused for 180 minutes. Citrulline (100 µM) or arginine (100 µM) was added with reperfusion and remained in the perfusion buffer for 180 minutes. Nω-nitro-l-arginine methyl ester (l-NAME) was used to antagonize NOS activity.</AbstractText>Citrulline increased load-free cell shortening of isolated adult rat cardiomyocytes and improved left ventricular developed pressure (LVDP) under normoxic conditions, indicating that citrulline can affect heart function. Ischemia/reperfusion caused a constitutive loss of function during 3 hours of reperfusion, whereas citrulline, but not arginine, improved the functional recovery during reperfusion. This effect was attenuated by co-administration of l-NAME. Although citrulline increased the formation of nitrite, l-NAME attenuated this effect indicating again a positive effect of citrulline on NO formation. Citrulline, but not arginine, increased the expression of arginase-1 (protein and mRNA) but l-NAME attenuated this effect again. Collectively, citrulline improved the post-ischemic recovery in an NO-dependent way.</AbstractText>Citrulline, known to block arginase and to support NO formation, improves the early functional recovery of post-ischemic hearts and may be an alternative to catecholamines to improve early post-ischemic recovery.</AbstractText>
|
2,334,916 |
Self-adaptive signal separation for non-contact heart rate estimation from facial video in realistic environments.
|
Recent research indicates that facial epidermis color varies with the rhythm of heat beats. It can be captured by consumer-level cameras and, astonishingly, be adopted to estimate heart rate (HR). The HR estimated remains not as precise as required in a practical environment where illumination interference, facial expressions, or motion artifacts are involved, although numerous methods have been proposed in the last few years. A novel algorithm is proposed to make non-contact HR estimation technique more robust.</AbstractText>First, the face of the subject is detected and tracked to follow the head movement. The facial region then falls into several blocks, and the chrominance feature of each block is extracted to establish a raw HR sub-signal. Self-adaptive signal separation is performed to separate the noiseless HR sub-signals from raw sub-signals. On that basis, the noiseless sub-signals full of HR information are selected using a weight-based scheme to establish the holistic HR signal, from which the average HR is computed adopting wavelet transform and data filtering.</AbstractText>Forty subjects took part in our experiments, whose facial videos were recorded by a normal webcam with the frame rate of 30 fps under ambient lighting conditions. The average HR estimated by our method correlates strongly with ground truth measurements, as indicated in experimental results measured in a static scenario with the Pearson correlation r  =  0.980 and a dynamic scenario with the Pearson correlation r  =  0.897. In addition, our method, compared to the newest method, decreases the error rate by 38.63% and increases the Pearson correlation by 15.59%.</AbstractText>This work proposes a robust method for non-contact HR measurement in a realistic environment. Results of comparative experiments indicate that our method out-performs state-of-the-art non-contact HR estimation methods in realistic environments.</AbstractText>
|
2,334,917 |
Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.
|
Twice a week carfilzomib at 27 mg/m2</sup> is approved for treatment of relapsed or refractory multiple myeloma. Phase 1/2 CHAMPION-1, the first study exploring once-weekly carfilzomib dosing, established the maximum tolerated dose at 70 mg/m2</sup> in combination with dexamethasone. We aimed to compare progression-free survival in patients with relapsed and refractory multiple myeloma given once weekly carfilzomib or twice weekly carfilzomib.</AbstractText>In this prespecified interim analysis of the randomised, open-label, phase 3 A.R.R.O.W. trial, we recruited patients (aged 18 years and older) with relapsed and refractory multiple myeloma previously treated with two or three treatments, including a proteasome inhibitor and immunomodulatory agent, from hospital, clinic, oncology or medical centres. Key eligibility criteria were refractory to most recent therapy (including bortezomib or ixazomib) with measurable disease, and Eastern Cooperative Oncology Group Performance Status of 0 or 1. Patients were randomly assigned (1:1) to receive carfilzomib once a week (70 mg/m2</sup>) or twice a week (27 mg/m2</sup>). The randomisation sequence was generated using a validated randomisation software and implemented using an interactive response technology system that assigned patients to treatment sequentially based on the randomisation sequence as patients were enrolled at participating clinical sites. Patients were stratified by International Staging System stage at study entry or baseline, whether or not they were refractory to bortezomib treatment, and age (block size of 4). The once weekly group received carfilzomib (30 min intravenous infusion) on days 1, 8, and 15 of all cycles (20 mg/m2</sup> day 1 [cycle 1]; 70 mg/m2</sup> thereafter). The twice weekly group received carfilzomib (10 min intravenous infusion) on days 1, 2, 8, 9, 15, and 16 (20 mg/m2</sup> days 1 and 2 during cycle 1; 27 mg/m2</sup> thereafter). All patients received dexamethasone (40 mg on days 1, 8, 15 [all cycles] and 22 [cycles 1-9 only]). Treatment continued until disease progression or unacceptable toxic effects. The primary objective was to compare progression-free survival between groups in the intention-to-treat population. Safety analysis was done in all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02412878, and is no longer enrolling patients.</AbstractText>Between September, 2015, and August, 2016, 578 patients were recruited from 118 sites. 478 patients were randomly assigned and included in the efficacy analyses (240 to receive once weekly carfilzomib; 238 to receive twice weekly carfilzomib). Median progression-free survival was higher in the once weekly group than the twice weekly group (11·2 months [95% CI 8·6-13·0] vs 7·6 months [5·8-9·2]; hazard ratio [HR] 0·69, 95% CI 0·54-0·83; p=0·0029). The incidence of grade 3 or worse adverse events was higher in the once weekly group than the twice weekly group (68% [n=161] vs 62% [n=145]); the most common events were anaemia, pneumonia, and thrombocytopenia (42 [18%] vs 42 [18%], 24 [10%] vs 16 [7%], and 17 [7%] vs 16 [7%], respectively for once weekly carfilzomib vs twice weekly carfilzomib). A lower proportion of patients had grade 3 or worse cardiac failure in the once weekly group (7 [3%]) than in the twice weekly group (10 [4%]). Treatment-related deaths occurred in five (2%) of 238 patients in the once weekly group (sepsis [n=1], death [n=1], acute lung injury [n=1], acute respiratory distress syndrome [n=1], and tumour lysis syndrome [n=1]) and in two (1%) of 235 patients in the twice weekly group (plasma cell myeloma [n=1] and congestive heart failure [n=1]). There were 58 deaths in the once weekly group and 68 deaths in the twice weekly group at the time of data cutoff.</AbstractText>Once weekly carfilzomib at 70 mg/m2</sup> significantly prolonged progression-free survival versus the twice weekly schedule. Overall safety was comparable between the groups. Once weekly carfilzomib appears safe and more effective with a convenient dosing regimen versus the twice weekly schedule for the treatment of patients with relapsed and refractory multiple myeloma.</AbstractText>Amgen, Inc.</AbstractText>Copyright © 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
|
2,334,918 |
Traditional Chinese medicine Qiliqiangxin attenuates phenylephrine-induced cardiac hypertrophy via upregulating PPARγ and PGC-1α.
|
Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown.</AbstractText>The effects of QLQX were investigated based on PE induced cardiac hypertrophy mouse models. Echocardiography and hematoxylin-eosin (HE) staining were used to determine cardiac function and cross-sectional area, respectively. Quantitative real time PCR (qRT-PCR) was used to determine ANP and BNP expressions. Based on primary neonatal rat ventricular cardiomyocytes (NRVMs) treated with PE, the cell size and expressions of ANP and BNP were determined by immunofluorescent staining and qRT-PCR, respectively. In addition, western blot was used to determine PPARγ and PGC-1α expressions.</AbstractText>In present study, we confirmed that QLQX could significantly attenuate cardiac hypertrophy in mice treated with PE. Then we showed that PPARγ and PGC-1α were downregulated in PE-induced cardiac hypertrophy, and QLQX could block the decrease of PPARγ and PGC-1α both in vitro</i> and in vivo</i>. Importantly, we found that PPARγ inhibitors or PGC-1α siRNAs eliminated the protective effects of QLQX on PE-induced cardiac hypertrophy.</AbstractText>Our study suggested that QLQX prevents from PE-induced cardiac hypertrophy by activating PPARγ and its coactivator PGC-1α.</AbstractText>
|
2,334,919 |
Low-energy ablation of anteroseptal accessory pathways in two dogs.<Pagination><StartPage>285</StartPage><EndPage>293</EndPage><MedlinePgn>285-293</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jvc.2018.05.001</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1760-2734(17)30209-6</ELocationID><Abstract><AbstractText>In humans, accessory pathways (APs) in an anteroseptal and midseptal position are often challenging to ablate because of their close proximity with the conduction pathways of the atrioventricular junction. The use of low-energy ablation techniques can be useful to reduce the risk of permanently damaging the atrioventricular node and the His bundle. This report describes the use of low-energy radiofrequency catheter ablation to successfully and permanently ablate anteroseptal APs in two dogs with orthodromic atrioventricular reciprocating tachycardia. In the first dog, a transient first degree atrioventricular block persisted for 30 s after radiofrequency energy delivery. In the second dog, transient paroxysmal atrioventricular conduction block was observed during the procedure but resolved within 3 days. First degree atrioventricular block was again identified 2 months later. In conclusion, anteroseptal APs can be effectively treated by low-energy radiofrequency catheter ablation with minimal and transient damage to the atrioventricular junction.</AbstractText><CopyrightInformation>Published by Elsevier B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Santilli</LastName><ForeName>R A</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>Clinica Veterinaria Malpensa, Viale Marconi 27, 21017 Samarate, Varese, Italy; Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Caivano</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126, Perugia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pariaut</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Birettoni</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126, Perugia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perego</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clinica Veterinaria Malpensa, Viale Marconi 27, 21017 Samarate, Varese, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Porciello</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126, Perugia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moïse</LastName><ForeName>N S</ForeName><Initials>NS</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>05</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Vet Cardiol</MedlineTA><NlmUniqueID>101163270</NlmUniqueID><ISSNLinking>1760-2734</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="N">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017115" MajorTopicYN="N">Catheter Ablation</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004283" MajorTopicYN="N">Dog Diseases</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013610" MajorTopicYN="N">Tachycardia</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054088" MajorTopicYN="N">Ventricular Septum</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Atrioventricular node</Keyword><Keyword MajorTopicYN="N">Atrioventricular reciprocating tachycardia</Keyword><Keyword MajorTopicYN="N">Bypass tract</Keyword><Keyword MajorTopicYN="N">Canine</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>11</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>4</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>5</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>11</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29859723</ArticleId><ArticleId IdType="doi">10.1016/j.jvc.2018.05.001</ArticleId><ArticleId IdType="pii">S1760-2734(17)30209-6</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">31643457</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK548127</ArticleId></ArticleIdList><Book><Publisher><PublisherName>National Institute of Diabetes and Digestive and Kidney Diseases</PublisherName><PublisherLocation>Bethesda (MD)</PublisherLocation></Publisher><BookTitle book="livertox">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury</BookTitle><PubDate><Year>2012</Year></PubDate><BeginningDate><Year>2012</Year></BeginningDate><Medium>Internet</Medium></Book><ArticleTitle book="livertox" part="Betablockers">Beta Adrenergic Blocking Agents
|
In humans, accessory pathways (APs) in an anteroseptal and midseptal position are often challenging to ablate because of their close proximity with the conduction pathways of the atrioventricular junction. The use of low-energy ablation techniques can be useful to reduce the risk of permanently damaging the atrioventricular node and the His bundle. This report describes the use of low-energy radiofrequency catheter ablation to successfully and permanently ablate anteroseptal APs in two dogs with orthodromic atrioventricular reciprocating tachycardia. In the first dog, a transient first degree atrioventricular block persisted for 30 s after radiofrequency energy delivery. In the second dog, transient paroxysmal atrioventricular conduction block was observed during the procedure but resolved within 3 days. First degree atrioventricular block was again identified 2 months later. In conclusion, anteroseptal APs can be effectively treated by low-energy radiofrequency catheter ablation with minimal and transient damage to the atrioventricular junction.<CopyrightInformation>Published by Elsevier B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Santilli</LastName><ForeName>R A</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>Clinica Veterinaria Malpensa, Viale Marconi 27, 21017 Samarate, Varese, Italy; Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Caivano</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126, Perugia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pariaut</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Birettoni</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126, Perugia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perego</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clinica Veterinaria Malpensa, Viale Marconi 27, 21017 Samarate, Varese, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Porciello</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126, Perugia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moïse</LastName><ForeName>N S</ForeName><Initials>NS</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>05</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Vet Cardiol</MedlineTA><NlmUniqueID>101163270</NlmUniqueID><ISSNLinking>1760-2734</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="N">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017115" MajorTopicYN="N">Catheter Ablation</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004283" MajorTopicYN="N">Dog Diseases</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013610" MajorTopicYN="N">Tachycardia</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054088" MajorTopicYN="N">Ventricular Septum</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Atrioventricular node</Keyword><Keyword MajorTopicYN="N">Atrioventricular reciprocating tachycardia</Keyword><Keyword MajorTopicYN="N">Bypass tract</Keyword><Keyword MajorTopicYN="N">Canine</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>11</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>4</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>5</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>11</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29859723</ArticleId><ArticleId IdType="doi">10.1016/j.jvc.2018.05.001</ArticleId><ArticleId IdType="pii">S1760-2734(17)30209-6</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">31643457</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK548127</ArticleId></ArticleIdList><Book><Publisher><PublisherName>National Institute of Diabetes and Digestive and Kidney Diseases</PublisherName><PublisherLocation>Bethesda (MD)</PublisherLocation></Publisher><BookTitle book="livertox">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury</BookTitle><PubDate><Year>2012</Year></PubDate><BeginningDate><Year>2012</Year></BeginningDate><Medium>Internet</Medium></Book><ArticleTitle book="livertox" part="Betablockers">Beta Adrenergic Blocking Agents</ArticleTitle><Language>eng</Language><PublicationType UI="D016454">Review</PublicationType><Abstract>The beta-adrenergic receptor antagonists (beta-blockers) are a family of agents that are widely used to treat hypertension, angina pectoris and cardiac arrhythmias. Beta-blockers are also used for migraine prophylaxis, to treat anxiety, to prevent essential tremor, and to block the side effects of hyperthyroidism. Nonspecific beta-blockers are also recommended for treatment of portal hypertension in patients with cirrhosis. The beta-blockers act by competing with beta-adrenergic agonists (such as epinephrine and norepinephrine) for beta-receptor sites. Beta-blockers are often categorized as “selective” or “non-selective” based upon whether they block both beta-1 receptors that are predominantly present in cardiac muscle and beta-2 receptors found in bronchial and smooth muscles. Beta-1 selective blockers are preferred for therapy of heart disease, whereas the nonselective beta-blockers are preferred as therapy to prevent recurrent variceal hemorrhage in patients with cirrhosis and portal hypertension. Nonselective beta-blockers (common brand name and the year of their approval for use in the United States) include propranolol (Inderal, 1967), nadolol (CorGard, 1979), pindolol (Visken, 1982), labetalol (Normodyne, Trandate, 1984), penbutolol (Levatol, 1987), sotalol (Betapace, 1992), carvedilol (Coreg, 1995), and timolol (Biocarden, 1995). Beta-1 selective blockers include metoprolol (Lopressor, Toprol, 1978), atenolol (Temormin, 1981), acebutolol (Sectral, 1984), betaxolol (Kerlone, 1985), esmolol (Brevibloc, 1986), bisoprolol (Zebeta, 1992) and nebivolol (Bystolic, 2008). Beta-blockers are some of the most frequently used medications in medicine and are usually well tolerated. Common side effects are those that are caused by the beta-adrenergic blockade and include bradycardia, fatigue, dizziness, depression, memory loss, insomnia, impotence, cold limbs and, less commonly, severe hypotension, heart failure and acute bronchospasm. Beta-blockers have been associated with a minimally increased rate of serum aminotransferase elevations and have rarely been associated with clinically apparent liver injury. Isolated case reports of idiosyncratic hepatotoxicity due to beta-blockers have been published, but there have been few case series. The case reports that have been published provide a general pattern of injury with a typical time to onset of 2 to 24 weeks and a hepatocellular pattern of serum enzyme elevations. Most cases have been mild and self-limiting, but fatal cases have been reported. Switching from one beta-blocker to another has not always resulted in recurrence of liver injury, although there have been only rare reports of such cross challenges. Most information on hepatotoxicity is available on the commonly used beta-blockers which include (and the number of prescriptions filled in 2007 for each): atenolol (42 million), metoprolol (27 million), propranolol (6.1 million), bisoprolol (4.3 million), carvedilol (2.9 million), labetalol (2.6 million), and nadolol (1.8 million). Labetalol and acebutolol have been associated with the most numbers of published cases (likelihood scores "C"), which is particularly striking in view of their relative frequency of use. Rare cases have been linked to atenolol, carvedilol and metoprolol therapy (likelihood scores "D"). The different beta-blockers are discussed separately with individual clinical cases, but references are combined and given at the end of this introductory section.
|
2,334,920 |
2-D Myocardial Deformation Imaging Based on RF-Based Nonrigid Image Registration.
|
Myocardial deformation imaging is a well-established echocardiographic technique for the assessment of myocardial function. Although some solutions make use of speckle tracking of the reconstructed B-mode images, others apply block matching (BM) on the underlying radio frequency (RF) data in order to increase sensitivity to small interframe motion and deformation. However, for both approaches, lateral motion estimation remains a challenge due to the relatively poor lateral resolution of the ultrasound image in combination with the lack of phase information in this direction. Hereto, nonrigid image registration (NRIR) of B-mode images has previously been proposed as an attractive solution. However, hereby, the advantages of RF-based tracking were lost. The aim of this paper was, therefore, to develop an NRIR motion estimator adapted to RF data sets. The accuracy of this estimator was quantified using synthetic data and was contrasted against a state-of-the-art BM solution. The results show that RF-based NRIR outperforms BM in terms of tracking accuracy, particularly, as hypothesized, in the lateral direction. Finally, this RF-based NRIR algorithm was applied clinically, illustrating its ability to estimate both in-plane velocity components in vivo.
|
2,334,921 |
Risk Prediction of Atrial Fibrillation Based on Electrocardiographic Interatrial Block.
|
The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person.</AbstractText>Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB.</AbstractText>IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.</AbstractText>© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.</CopyrightInformation>
|
2,334,922 |
Longitudinal study of health, disease and access to care in rural Victoria: the Crossroads-II study: methods.
|
High quality, contemporary data regarding patterns of chronic disease is essential for planning by health services, policy makers and local governments, but surprisingly scarce, including in rural Australia. This dearth of data occurs despite the recognition that rural Australians live with high rates of ill health, poor health behaviours and restricted access to health services. Crossroads-II is set in the Goulburn Valley, a rural region of Victoria, Australia 100-300 km north of metropolitan Melbourne. It is primarily an irrigated agricultural area. The aim of the study is to identify changes in the prevalence of key chronic health conditions including the extent of undiagnosed and undermanaged disease, and association with access to care, over a 15 year period.</AbstractText><AbstractText Label="METHODS/DESIGN">This study is a 15 year follow up from the 2000-2003 Crossroads-I study (2376 households participated). Crossroads-II includes a similar face to face household survey of 3600 randomly selected households across four towns of sizes 6300 to 49,800 (50% sampled in the larger town with the remainder sampled equally from the three smaller towns). Self-reported health, health behaviour and health service usage information is verified and supplemented in a nested sub-study of 900 randomly selected adult participants in 'clinics' involving a range of additional questionnaires and biophysical measurements. The study is expected to run from October 2016 to December 2018.</AbstractText>Besides providing epidemiological and health service utilisation information relating to different diseases and their risk factors in towns of different sizes, the results will be used to develop a composite measure of health service access. The importance of access to health services will be investigated by assessing the correlation of this measure with rates of undiagnosed and undermanaged disease at the mesh block level. Results will be shared with partner organisations to inform service planning and interventions to improve health outcomes for local people.</AbstractText>
|
2,334,923 |
Advanced interatrial block predicts new-onset atrial fibrillation and ischemic stroke in patients with heart failure: The "Bayes' Syndrome-HF" study.
|
Advanced interatrial block (IAB) is characterized by a prolonged (≥120 ms) and bimodal P wave in the inferior leads. The association between advanced IAB and atrial fibrillation (AF) is known as "Bayes' Syndrome", and there is scarce information about it in heart failure (HF). We examined the prevalence of IAB and whether advanced IAB could predict new-onset AF and/or stroke in HF patients.</AbstractText>The prospective observational "Bayes' Syndrome-HF" study included consecutive outpatients with chronic HF. The primary endpoints were new-onset AF, ischemic stroke, and the composite of both. A secondary endpoint included all-cause death alone or in combination with the primary endpoint. Comprehensive multivariable Cox regression analyses were performed. Among 1050 consecutive patients, 536 (51.0%) were in sinus rhythm, 464 with a measurable P wave are the focus of this study. Two-hundred and sixty patients (56.0%) had normal atrial conduction, 95 (20.5%) partial IAB, and 109 (23.5%) advanced IAB. During a mean follow-up of 4.5 ± 2.1 years, 235 patients experienced all-cause death, new-onset AF, or stroke. In multivariable comprehensive Cox regression analyses, advanced IAB was associated with new-onset AF (HR 2.71 [1.61-4.56], P < 0.001), ischemic stroke (HR 3.02 [1.07-8.53], P = 0.04), and the composite of both (HR 2.42 [1.41-4.15], P < 0.001).</AbstractText>In patients with HF advanced IAB predicts new-onset AF and ischemic stroke. Future studies must assess whether anticoagulant treatment in Bayes' Syndrome leads to better outcomes in HF.</AbstractText>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation>
|
2,334,924 |
PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project.
|
The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.</AbstractText>BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials.</AbstractText>The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86-0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18-0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78-0.85).</AbstractText>BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.</AbstractText>Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
|
2,334,925 |
Glibenclamide Prevents Hypoglycemia-Induced Fatal Cardiac Arrhythmias in Rats.<Pagination><StartPage>2614</StartPage><EndPage>2620</EndPage><MedlinePgn>2614-2620</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1210/en.2018-00419</ELocationID><Abstract><AbstractText>Sulfonylureas increase the incidence of severe hypoglycemia in people with type 2 diabetes and might increase the risk of sudden cardiac death. Sulfonylureas stimulate insulin secretion by closing pancreatic ATP-sensitive potassium ion (KATP) channels. To investigate the role of KATP channel modulators on cardiac arrhythmias and mortality in the setting of severe hypoglycemia, adult Sprague-Dawley rats underwent hyperinsulinemic (0.2 U/kg/min) severe hypoglycemic (10 to 15 mg/dL) clamps with continuous electrocardiography. The rats were randomized for treatment with intravenous vehicle (VEH), the sulfonylurea glibenclamide (GLIB; KATP channel blocker; 5 mg/kg/h), or diazoxide (DIAZ; KATP channel opener; 5 mg/kg/h). The results demonstrated that GLIB completely prevented first-degree heart block compared with VEH (0.18 ± 0.09/min) and DIAZ (0.2 ± 0.05/min). Second-degree heart block was significantly reduced with GLIB (0.12 ± 0.1/min) compared with VEH (0.6 ± 0.2/min) and DIAZ (6.9 ± 3/min). The incidence of third-degree heart block was completely prevented by GLIB compared with VEH (67%) and DIAZ (87.5%). Hypoglycemia-induced mortality was completely prevented by GLIB compared with VEH (60%) and DIAZ (82%). In conclusion, although GLIB increases the risk of hypoglycemia by increasing insulin secretion, these results have demonstrated a paradoxical protective role of GLIB against severe hypoglycemia-induced fatal cardiac arrhythmias.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Reno</LastName><ForeName>Candace M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bayles</LastName><ForeName>Justin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Skinner</LastName><ForeName>Allie</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fisher</LastName><ForeName>Simon J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 NS070235</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 DK091317</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Endocrinology</MedlineTA><NlmUniqueID>0375040</NlmUniqueID><ISSNLinking>0013-7227</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007328">Insulin</NameOfSubstance></Chemical><Chemical><RegistryNumber>O5CB12L4FN</RegistryNumber><NameOfSubstance UI="D003981">Diazoxide</NameOfSubstance></Chemical><Chemical><RegistryNumber>SX6K58TVWC</RegistryNumber><NameOfSubstance UI="D005905">Glyburide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Endocrinology. 2018 Aug 1;159(8):3081-3082</RefSource><PMID Version="1">29955856</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001145" MajorTopicYN="N">Arrhythmias, Cardiac</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003981" MajorTopicYN="N">Diazoxide</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005905" MajorTopicYN="N">Glyburide</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007003" MajorTopicYN="N">Hypoglycemia</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007328" MajorTopicYN="N">Insulin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011897" MajorTopicYN="N">Random Allocation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>5</Month><Day>3</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>5</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>5</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>2</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>5</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29800118</ArticleId><ArticleId IdType="pmc">PMC6669817</ArticleId><ArticleId IdType="doi">10.1210/en.2018-00419</ArticleId><ArticleId IdType="pii">5001723</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Terry T, Raravikar K, Chokrungvaranon N, Reaven PD. Does aggressive glycemic control benefit macrovascular and microvascular disease in type 2 diabetes? Insights from ACCORD, ADVANCE, and VADT. Curr Cardiol Rep. 2012;14(1):79–88.</Citation><ArticleIdList><ArticleId IdType="pubmed">22160862</ArticleId></ArticleIdList></Reference><Reference><Citation>ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2572.</Citation><ArticleIdList><ArticleId IdType="pubmed">18539916</ArticleId></ArticleIdList></Reference><Reference><Citation>Mellbin LG, Rydén L, Riddle MC, Probstfield J, Rosenstock J, Díaz R, Yusuf S, Gerstein HC; ORIGIN Trial Investigators . Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial. Eur Heart J. 2013;34(40):3137–3144.</Citation><ArticleIdList><ArticleId IdType="pubmed">23999452</ArticleId></ArticleIdList></Reference><Reference><Citation>Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT; Action to Control Cardiovascular Risk in Diabetes Study Group . Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–2559.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4551392</ArticleId><ArticleId IdType="pubmed">18539917</ArticleId></ArticleIdList></Reference><Reference><Citation>Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ, Sprung C, Young JD, Su S, Heritier S, Li Q, Bompoint S, Billot L, Crampton L, Darcy F, Jayne K, Kumarasinghe V, Little L, McEvoy S, MacMahon S, Pandey S, Ryan S, Shukla R, Vijayan B, Atherton S, Bell J, Hadfield L, Hourigan C, McArthur C, Newby L, Simmonds C, Buhr H, Eccleston M, McGuinness S, Parke R, Bellomo R, Bates S, Goldsmith D, Mercer I, O’Sullivan K, Gazzard R, Hill D, Tauschke C, Ghelani D, Nand K, Reece G, Sara T, Elliott S, Ernest D, Hamilton A, Ashley R, Bailey A, Crowfoot E, Gissane J, Mitchell I, Ranse J, Whiting J, Douglas K, Milliss D, Tan J, Wong H, Blythe D, Palermo A, Hardie M, Harrigan P, McFadyen B, Micallef S, Parr M, Boase A, Tai J, Williams A, Cole L, Seppelt I, Weisbrodt L, Whereat S, Flanagan A, Liang J, Bass F, Campbell M, Hammond N, Nicholson L, Shehabi Y, Foote J, Peake S, Williams P, Deans R, Fourie C, Lassig-Smith M, Lipman J, Stuart J, Bell A, Field T, McAllister R, Marsden K, Turner A, Ankers S, Bird S, Finfer S, Lee R, O’Connor A, Potter J, Ramakrishnan N, Raper R, Dhiacou V, Girling K, Jovanovska A, Myburgh J, Groves N, Holmes J, Santamaria J, Smith R, Baker S, Roberts B, Andrews L, Dinsdale R, Fenton R, Mackle D, Mortimer S, French C, Little L, Raunow H, Gales M, Hill F, Rachakonda S, Rogan D, Allsop C, Higgins L, Robinson B, Champagne K, Doig C, Knox L, Taylor P, Wilson C, Drover J, Hammond S, Mann E, Myers M, Robinson A, Harvey J, Skrobik Y, Baumgartner A, Meade L, Vlahakis N, Ethier C, Kramer-Kile M, Mehta S, Gaudert C, Kanji S, McArdle T, Watpool I, Clarke F, Cook D, McDonald E, Tkaczyk A, Marshall J, Morrissey J, Porretta K, Smith O, Wen V, Ashley BJ, Dodek P, Mans S, Bojilov B, Code K, Fowler R, Marinoff N, Chu L, Granton J, McGrath-Chong M, Steinberg M, Ferguson N, Go S, Matte A, Rosenberg J, Stevenson J, Jacka M, Sonnema L, Autio R, Chittock D, Davies D, Ganz P, Gardner M, Logie S, Smith L, Atkins L, Auld F, Stewart M, Wood G; NICE-SUGAR Study Investigators . Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283–1297.</Citation><ArticleIdList><ArticleId IdType="pubmed">19318384</ArticleId></ArticleIdList></Reference><Reference><Citation>Cryer PE. Death during intensive glycemic therapy of diabetes: mechanisms and implications. Am J Med. 2011;124(11):993–996.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3464092</ArticleId><ArticleId IdType="pubmed">22017775</ArticleId></ArticleIdList></Reference><Reference><Citation>Chow E, Bernjak A, Williams S, Fawdry RA, Hibbert S, Freeman J, Sheridan PJ, Heller SR. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes. 2014;63(5):1738–1747.</Citation><ArticleIdList><ArticleId IdType="pubmed">24757202</ArticleId></ArticleIdList></Reference><Reference><Citation>Reno CM, Daphna-Iken D, Chen YS, VanderWeele J, Jethi K, Fisher SJ. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation. Diabetes. 2013;62(10):3570–3581.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3781452</ArticleId><ArticleId IdType="pubmed">23835337</ArticleId></ArticleIdList></Reference><Reference><Citation>American Diabetes Association 8. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S73–S85.</Citation><ArticleIdList><ArticleId IdType="pubmed">29222379</ArticleId></ArticleIdList></Reference><Reference><Citation>Montvida O, Shaw J, Atherton JJ, Stringer F, Paul SK. Long-term trends in antidiabetes drug usage in the U.S.: real-world evidence in patients newly diagnosed with type 2 diabetes. Diabetes Care. 2018;41(1):69–78.</Citation><ArticleIdList><ArticleId IdType="pubmed">29109299</ArticleId></ArticleIdList></Reference><Reference><Citation>Leonard CE, Hennessy S, Han X, Siscovick DS, Flory JH, Deo R. Pro- and antiarrhythmic actions of sulfonylureas: mechanistic and clinical evidence. Trends Endocrinol Metab. 2017;28(8):561–586.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5522643</ArticleId><ArticleId IdType="pubmed">28545784</ArticleId></ArticleIdList></Reference><Reference><Citation>Tosaki A, Engelman DT, Engelman RM, Das DK. Diabetes and ATP-sensitive potassium channel openers and blockers in isolated ischemic/reperfused hearts. J Pharmacol Exp Ther. 1995;275(3):1115–1123.</Citation><ArticleIdList><ArticleId IdType="pubmed">8531071</ArticleId></ArticleIdList></Reference><Reference><Citation>Engler RL, Yellon DM. Sulfonylurea KATP blockade in type II diabetes and preconditioning in cardiovascular disease: time for reconsideration. Circulation. 1996;94(9):2297–2301.</Citation><ArticleIdList><ArticleId IdType="pubmed">8901685</ArticleId></ArticleIdList></Reference><Reference><Citation>Garratt KN, Brady PA, Hassinger NL, Grill DE, Terzic A, Holmes DR Jr. Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction. J Am Coll Cardiol. 1999;33(1):119–124.</Citation><ArticleIdList><ArticleId IdType="pubmed">9935017</ArticleId></ArticleIdList></Reference><Reference><Citation>Cole WC, McPherson CD, Sontag D, Atp-Regulated K. ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage. Circ Res. 1991;69(3):571–581.</Citation><ArticleIdList><ArticleId IdType="pubmed">1908354</ArticleId></ArticleIdList></Reference><Reference><Citation>Kantor PF, Coetzee WA, Carmeliet EE, Dennis SC, Opie LH. Reduction of ischemic K+ loss and arrhythmias in rat hearts: effect of glibenclamide, a sulfonylurea. Circ Res. 1990;66(2):478–485.</Citation><ArticleIdList><ArticleId IdType="pubmed">2105170</ArticleId></ArticleIdList></Reference><Reference><Citation>Hamby WM, Jankowski GJ, Pouget JM, Dunea G, Gantt CL. Intravenous use of diazoxide in treatment of severe hypertension. Circulation. 1968;37(2):169–174.</Citation></Reference><Reference><Citation>Kane GC, Liu XK, Yamada S, Olson TM, Terzic A. Cardiac KATP channels in health and disease. J Mol Cell Cardiol. 2005;38(6):937–943.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2736958</ArticleId><ArticleId IdType="pubmed">15910878</ArticleId></ArticleIdList></Reference><Reference><Citation>Foster MN, Coetzee WA. KATP channels in the cardiovascular system. Physiol Rev. 2016;96(1):177–252.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4698399</ArticleId><ArticleId IdType="pubmed">26660852</ArticleId></ArticleIdList></Reference><Reference><Citation>Evans ML, McCrimmon RJ, Flanagan DE, Keshavarz T, Fan X, McNay EC, Jacob RJ, Sherwin RS. Hypothalamic ATP-sensitive K+ channels play a key role in sensing hypoglycemia and triggering counterregulatory epinephrine and glucagon responses. Diabetes. 2004;53(10):2542–2551.</Citation><ArticleIdList><ArticleId IdType="pubmed">15448082</ArticleId></ArticleIdList></Reference><Reference><Citation>George PS, Tavendale R, Palmer CN, McCrimmon RJ. Diazoxide improves hormonal counterregulatory responses to acute hypoglycemia in long-standing type 1 diabetes. Diabetes. 2015;64(6):2234–2241.</Citation><ArticleIdList><ArticleId IdType="pubmed">25591873</ArticleId></ArticleIdList></Reference><Reference><Citation>Reno CM, VanderWeele J, Bayles J, Litvin M, Skinner A, Jordan A, Daphna-Iken D, Fisher SJ. Severe hypoglycemia-induced fatal cardiac arrhythmias are augmented by diabetes and attenuated by recurrent hypoglycemia. Diabetes. 2017;66(12):3091–3097.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5697941</ArticleId><ArticleId IdType="pubmed">28887311</ArticleId></ArticleIdList></Reference><Reference><Citation>El-Reyani NE, Baczkó I, Leprán I, Papp JG. Effect of glibenclamide and glimepiride treatment on the development of myocardial infarction in rats. Acta Physiol Hung. 2000;87(2):173–184.</Citation><ArticleIdList><ArticleId IdType="pubmed">11205966</ArticleId></ArticleIdList></Reference><Reference><Citation>Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care. 2008;31(11):2086–2091.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2571051</ArticleId><ArticleId IdType="pubmed">18782901</ArticleId></ArticleIdList></Reference><Reference><Citation>Forst T, Hanefeld M, Jacob S, Moeser G, Schwenk G, Pfützner A, Haupt A. Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Diab Vasc Dis Res. 2013;10(4):302–314.</Citation><ArticleIdList><ArticleId IdType="pubmed">23291340</ArticleId></ArticleIdList></Reference><Reference><Citation>Simpson SH, Majumdar SR, Tsuyuki RT, Eurich DT, Johnson JA. Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. Can Med Assoc J. 2006;174:169–174.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1329454</ArticleId><ArticleId IdType="pubmed">16415461</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29799003</PMID><DateCompleted><Year>2018</Year><Month>10</Month><Day>05</Day></DateCompleted><DateRevised><Year>2018</Year><Month>10</Month><Day>05</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0023-1207</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2018</Year></PubDate></JournalIssue><Title>Khirurgiia</Title><ISOAbbreviation>Khirurgiia (Mosk)</ISOAbbreviation></Journal>[Partial atrioventricular septal defect repair in 72 years old patient].
|
Sulfonylureas increase the incidence of severe hypoglycemia in people with type 2 diabetes and might increase the risk of sudden cardiac death. Sulfonylureas stimulate insulin secretion by closing pancreatic ATP-sensitive potassium ion (KATP) channels. To investigate the role of KATP channel modulators on cardiac arrhythmias and mortality in the setting of severe hypoglycemia, adult Sprague-Dawley rats underwent hyperinsulinemic (0.2 U/kg/min) severe hypoglycemic (10 to 15 mg/dL) clamps with continuous electrocardiography. The rats were randomized for treatment with intravenous vehicle (VEH), the sulfonylurea glibenclamide (GLIB; KATP channel blocker; 5 mg/kg/h), or diazoxide (DIAZ; KATP channel opener; 5 mg/kg/h). The results demonstrated that GLIB completely prevented first-degree heart block compared with VEH (0.18 ± 0.09/min) and DIAZ (0.2 ± 0.05/min). Second-degree heart block was significantly reduced with GLIB (0.12 ± 0.1/min) compared with VEH (0.6 ± 0.2/min) and DIAZ (6.9 ± 3/min). The incidence of third-degree heart block was completely prevented by GLIB compared with VEH (67%) and DIAZ (87.5%). Hypoglycemia-induced mortality was completely prevented by GLIB compared with VEH (60%) and DIAZ (82%). In conclusion, although GLIB increases the risk of hypoglycemia by increasing insulin secretion, these results have demonstrated a paradoxical protective role of GLIB against severe hypoglycemia-induced fatal cardiac arrhythmias.
|
2,334,926 |
Simulated Altitude via Re-Breathing Creates Arterial Hypoxemia but Fails to Improve Elements of Running Performance.
|
Acclimatization to altitude has been shown to improve elements of performance. Use of simulated altitude is popular among athletes across the sports spectrum. This work was on a handheld, re-breathing device touted to enhance performance. Seven recreationally-trained athletes used the device for 18 hours over the course of the 37-day intervention trial. The elevations simulated were progressively increased from 1,524m to 6,096m. To ascertain potential efficacy, four performance trials were included (familiarization, baseline, and 2 follow-ups). Hematological (hematocrit, hemoglobin, and lactate), physiological (respiratory exchange ratio, heart rate, and oxygen consumption), and perceptual (Borg's RPE) variables were monitored at rest, during two steady state running economy stages, and at maximal effort during each visit. The device is clearly capable of creating arterial hypoxemic conditions equating to high altitude. This fact is exemplified by average pulse oximetry values of approximately 78.5% in the final 6-day block of simulation. At the same time, there were no changes observed in any hematological (<i>p</i>>0.05), physiological (<i>p</i>>0.05), or perceptual (<i>p</i>>0.05) variable at either follow-up performance trial. Relative VO<sub>2</sub> data was analyzed with a 15-breath moving average sampling frequency in accordance with our recent findings (Scheadler et al.) reported in Medicine and Science in Sports and Exercise. Effect sizes are reported within, but most were trivial (d=0.0-0.19). Overall, findings align with speculation that a more robust altitude stimulus than can be offered by short-term arterial hypoxemia is required for changes to be evidenced. The device has shown some promise in other work, but our data is not supportive.
|
2,334,927 |
Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study.
|
<AbstractText Label="BACKGROUND/AIMS" NlmCategory="OBJECTIVE">Ultrasound-guided supraclavicular brachial plexus block (BPB) has come into wider use as a regional anesthetic during upper limb operations. This study assessed the neurological and hemodynamic changes and gene expression after co-administration of midazolam or neostigmine with bupivacaine during supraclavicular BPB.</AbstractText>The study involved 90 adults divided into three groups: control (bupivacaine), midazolam (bupivacaine plus midazolam), and neostigmine (bupivacaine plus neostigmine). Blood samples were taken and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels were measured by real-time PCR, and oxidative stress markers were identified. In addition to the hemodynamic variables, the onset and duration of sensory and motor blockades, duration of analgesia, pain scores, time of first request for an analgesic, and amounts of analgesics ingested were evaluated.</AbstractText>Compared with the control and neostigmine groups, the midazolam group experienced longer sensory and motor blockades, prolonged analgesia, lower pain scores at 12 h and 24 h, and lower need for postoperative analgesics. Moreover, the midazolam group exhibited lower oxidative stress markers with a higher fold change in IL-6 and TNF-α mRNA levels.</AbstractText>Midazolam co-administered with bupivacaine provided better analgesic quality than did neostigmine with bupivacaine. This might be due to its superior antioxidant and anti-inflammatory effects.</AbstractText>© 2018 The Author(s). Published by S. Karger AG, Basel.</CopyrightInformation>
|
2,334,928 |
The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells.
|
Formation of the vasculature by angiogenesis is critical for proper development, but angiogenesis also contributes to the pathogenesis of various disorders, including cancer and cardiovascular diseases. Vascular endothelial zinc finger 1 (Vezf1), is a Krüppel-like zinc finger protein that plays a vital role in vascular development. However, the mechanism by which Vezf1 regulates this process is not fully understood. Here, we show that <i>Vezf1</i><sup>-/-</sup> mouse embryonic stem cells (ESC) have significantly increased expression of a stem cell factor, Cbp/p300-interacting transactivator 2 (Cited2). Compared with WT ESCs, <i>Vezf1</i><sup>-/-</sup> ESCs inefficiently differentiated into endothelial cells (ECs), which exhibited defects in the tube-formation assay. These defects were due to reduced activation of EC-specific genes concomitant with lower enrichment of histone 3 acetylation at Lys<sup>27</sup> (H3K27) at their promoters. We hypothesized that overexpression of Cited2 in <i>Vezf1</i><sup>-/-</sup> cells sequesters P300/CBP away from the promoters of proangiogenic genes and thereby contributes to defective angiogenesis in these cells. This idea was supported by the observation that shRNA-mediated depletion of Cited2 significantly reduces the angiogenic defects in the <i>Vezf1</i><sup>-/-</sup> ECs. In contrast to previous studies that have focused on the role of Vezf1 as a transcriptional activator of proangiogenic genes, our findings have revealed a role for Vezf1 in modulating the expression of the antiangiogenic factor Cited2. Vezf1 previously has been characterized as an insulator protein, and our results now provide insights into the mechanism, indicating that Vezf1 can block inappropriate, nonspecific interactions of promoters with <i>cis</i>-located enhancers, preventing aberrant promoter activation.
|
2,334,929 |
Effect of the patient education - Learning and Coping strategies - in cardiac rehabilitation on return to work at one year: a randomised controlled trial show (LC-REHAB).
|
Personal resources are identified as important for the ability to return to work (RTW) for patients with ischaemic heart disease (IHD) or heart failure (HF) undergoing cardiac rehabilitation (CR). The patient education 'Learning and Coping' (LC) addresses personal resources through a pedagogical approach. This trial aimed to assess effect of adding LC strategies in CR compared to standard CR measured on RTW status at one-year follow-up after CR.</AbstractText>In an open parallel randomised controlled trial, patients with IHD or HF were block-randomised in a 1:1 ratio to the LC arm (LC plus CR) or the control arm (CR alone) across three Danish hospital units. Eligible patients were aged 18 to ≤60 and had not left the labour market. The intervention was developed from an inductive pedagogical approach consisting of individual interviews and group based teaching by health professionals with experienced patients as co-educators. The control arm consisted of deductive teaching (standard CR). RTW status was derived from the Danish Register for Evaluation of Marginalisation (DREAM). Blinding was not possible. The effect was evaluated by logistic regression analysis and reported as crude and adjusted odds ratios (OR) with 95% confidence interval (CI).</AbstractText>The population for the present analysis was N = 244 (LC arm: n = 119 versus control arm: n = 125). No difference in RTW status was found at one year across arms (LC arm: 64.7% versus control arm: 68.8%, adjusted odds ratio OR: 0.76, 95% CI: 0.43-1.31).</AbstractText>Addition of LC strategies in CR showed no improvement in RTW at one year follow-up.</AbstractText>www.clinicaltrials.gov identifier NCT01668394. First Posted: August 20, 2012.</AbstractText>
|
2,334,930 |
Evaluation of cardiac arrhythmic risks using a rabbit model of left ventricular systolic dysfunction.<Pagination><StartPage>145</StartPage><EndPage>155</EndPage><MedlinePgn>145-155</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejphar.2018.05.026</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0014-2999(18)30291-7</ELocationID><Abstract><AbstractText>Patients with heart disease have a higher risk to develop cardiac arrhythmias, either spontaneously or drug-induced. In this study, we have used a rabbit model of myocardial infarction (MI) with severe left ventricular systolic dysfunction (LVSD) to study potential drug-induced cardiac risks with N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (flecainide). Upon ligation of the left circumflex arteries, male New Zealand White rabbits developed a large MI and moderate or severe LVSD 7 weeks after surgery, in comparison to SHAM-operated animals. Subsequently, animals were exposed to escalating doses of flecainide (0.25-4 mg/kg) or solvent. Electrocardiograms (ECG) were recorded before surgery, 1 and 7 weeks after surgery and continuously during the drug protocol. The ECG biomarker iCEB (index of Cardio-Electrophysiological Balance = QT/QRS ratio) was calculated. During the ECG recording at week 1 and week 7 post MI, rabbits had no spontaneous cardiac arrhythmias. When rabbits were exposed to escalating doses of flecainide, 2 out of 5 rabbits with MI and moderate LVSD versus 0 out of 5 solvent-treated rabbits developed arrhythmias, such as ventricular tachycardia/ventricular fibrillation. These were preceded by a marked decrease of iCEB just before the onset (from 4.09 to 2.42 and from 5.56 to 2.25, respectively). Furthermore, 1 out of 5 MI rabbits with moderate LVSD and 1 out of 7 MI rabbits with severe LVSD developed total atrioventricular block after flecainide infusion and died. This rabbit model of MI and severe LVSD may be useful for preclinical evaluation of drug (similar mechanism as flecainide)-induced arrhythmic risks, which might be predicted by iCEB.</AbstractText><CopyrightInformation>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hemmeryckx</LastName><ForeName>Bianca</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feng</LastName><ForeName>Yuanbo</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Radiology, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frederix</LastName><ForeName>Liesbeth</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lox</LastName><ForeName>Marleen</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trenson</LastName><ForeName>Sander</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Cardiology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vreeken</LastName><ForeName>Rob</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Metabolomics, Pharmacokinetics, Dynamics and Metabolism Discovery Sciences, Janssen Pharmaceutical NV, Beerse, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Hua Rong</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Translational Sciences, Safety Pharmacology Research, Janssen Research & Development, Janssen Pharmaceutical NV, Beerse, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallacher</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Translational Sciences, Safety Pharmacology Research, Janssen Research & Development, Janssen Pharmaceutical NV, Beerse, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ni</LastName><ForeName>Yicheng</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Radiology, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lijnen</LastName><ForeName>H Roger</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>05</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Eur J Pharmacol</MedlineTA><NlmUniqueID>1254354</NlmUniqueID><ISSNLinking>0014-2999</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>K94FTS1806</RegistryNumber><NameOfSubstance UI="D005424">Flecainide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001145" MajorTopicYN="N">Arrhythmias, Cardiac</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005424" MajorTopicYN="N">Flecainide</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012306" MajorTopicYN="N">Risk</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013599" MajorTopicYN="Y">Systole</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018487" MajorTopicYN="N">Ventricular Dysfunction, Left</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Atrioventricular block</Keyword><Keyword MajorTopicYN="N">Flecainide</Keyword><Keyword MajorTopicYN="N">Left ventricular systolic dysfunction</Keyword><Keyword MajorTopicYN="N">Myocardial infarction</Keyword><Keyword MajorTopicYN="N">Ventricular tachycardia/ventricular fibrillation</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>2</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>5</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>5</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>10</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29782862</ArticleId><ArticleId IdType="doi">10.1016/j.ejphar.2018.05.026</ArticleId><ArticleId IdType="pii">S0014-2999(18)30291-7</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">29782260</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>16</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-9040</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2018</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Kardiologiia</Title><ISOAbbreviation>Kardiologiia</ISOAbbreviation></Journal>[Polymorphisms of the SCN10A Gene in Patients With Sick Sinus Syndrome].<Pagination><StartPage>53</StartPage><EndPage>59</EndPage><MedlinePgn>53-59</MedlinePgn></Pagination><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">To study association of rs6795970 polymorphism of SCN10A gene with development of idiopathic sick sinus syndrome (ISSS).</AbstractText><AbstractText Label="MATERIALS AND METHODS" NlmCategory="METHODS">We examined 109 patients with ISSS, 59 their healthy 1‑st-, 2‑nd-, and 3‑rd-degree relatives, and 630 controls. Patients with ISSS were divided into subgroups according to gender and clinical variant of the disease. All patients underwent cardiologic examination and molecular genetic testing of DNA.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">We revealed significant preponderance of homozygous genotype with rare allele of the studied gene among patients with ISSS compared with control group. In addition, this genotype significantly prevailed among men with SSSU in comparison with the control group.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Genotype AA of the SCN10A gene is associated with a predisposition to the development of ISSS.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Niculina</LastName><ForeName>S Y</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marilovceva</LastName><ForeName>O V</ForeName><Initials>OV</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chernova</LastName><ForeName>A A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tret'jakova</LastName><ForeName>S S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nikulin</LastName><ForeName>D A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maksimov</LastName><ForeName>V N</ForeName><Initials>VN</Initials><AffiliationInfo><Affiliation>Federal State Budgetary Institution, "Research Institute of Therapy and Preventive Medicine" at the Siberian Branch of Russian Academy of Medical Sciences.</Affiliation></AffiliationInfo></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Kardiologiia</MedlineTA><NlmUniqueID>0376351</NlmUniqueID><ISSNLinking>0022-9040</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D062559">NAV1.8 Voltage-Gated Sodium Channel</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C568317">SCN10A protein, human</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D005787" MajorTopicYN="N">Gene Frequency</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005838" MajorTopicYN="N">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D062559" MajorTopicYN="N">NAV1.8 Voltage-Gated Sodium Channel</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012804" MajorTopicYN="Y">Sick Sinus Syndrome</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">SCN10A gene</Keyword><Keyword MajorTopicYN="N">genetic polymorphism</Keyword><Keyword MajorTopicYN="N">sick sinus syndrome</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>5</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29782260</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">29782250</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>21</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-9040</ISSN><JournalIssue CitedMedium="Print"><Issue>S2</Issue><PubDate><MedlineDate>2018 SFeb</MedlineDate></PubDate></JournalIssue><Title>Kardiologiia</Title><ISOAbbreviation>Kardiologiia</ISOAbbreviation></Journal>[Effect of right ventricular myocardial contractility on the response to cardiac resynchronization therapy].
|
Patients with heart disease have a higher risk to develop cardiac arrhythmias, either spontaneously or drug-induced. In this study, we have used a rabbit model of myocardial infarction (MI) with severe left ventricular systolic dysfunction (LVSD) to study potential drug-induced cardiac risks with N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (flecainide). Upon ligation of the left circumflex arteries, male New Zealand White rabbits developed a large MI and moderate or severe LVSD 7 weeks after surgery, in comparison to SHAM-operated animals. Subsequently, animals were exposed to escalating doses of flecainide (0.25-4 mg/kg) or solvent. Electrocardiograms (ECG) were recorded before surgery, 1 and 7 weeks after surgery and continuously during the drug protocol. The ECG biomarker iCEB (index of Cardio-Electrophysiological Balance = QT/QRS ratio) was calculated. During the ECG recording at week 1 and week 7 post MI, rabbits had no spontaneous cardiac arrhythmias. When rabbits were exposed to escalating doses of flecainide, 2 out of 5 rabbits with MI and moderate LVSD versus 0 out of 5 solvent-treated rabbits developed arrhythmias, such as ventricular tachycardia/ventricular fibrillation. These were preceded by a marked decrease of iCEB just before the onset (from 4.09 to 2.42 and from 5.56 to 2.25, respectively). Furthermore, 1 out of 5 MI rabbits with moderate LVSD and 1 out of 7 MI rabbits with severe LVSD developed total atrioventricular block after flecainide infusion and died. This rabbit model of MI and severe LVSD may be useful for preclinical evaluation of drug (similar mechanism as flecainide)-induced arrhythmic risks, which might be predicted by iCEB.<CopyrightInformation>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hemmeryckx</LastName><ForeName>Bianca</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feng</LastName><ForeName>Yuanbo</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Radiology, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frederix</LastName><ForeName>Liesbeth</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lox</LastName><ForeName>Marleen</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trenson</LastName><ForeName>Sander</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Cardiology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vreeken</LastName><ForeName>Rob</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Metabolomics, Pharmacokinetics, Dynamics and Metabolism Discovery Sciences, Janssen Pharmaceutical NV, Beerse, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Hua Rong</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Translational Sciences, Safety Pharmacology Research, Janssen Research & Development, Janssen Pharmaceutical NV, Beerse, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallacher</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Translational Sciences, Safety Pharmacology Research, Janssen Research & Development, Janssen Pharmaceutical NV, Beerse, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ni</LastName><ForeName>Yicheng</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Radiology, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lijnen</LastName><ForeName>H Roger</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>05</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Eur J Pharmacol</MedlineTA><NlmUniqueID>1254354</NlmUniqueID><ISSNLinking>0014-2999</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>K94FTS1806</RegistryNumber><NameOfSubstance UI="D005424">Flecainide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001145" MajorTopicYN="N">Arrhythmias, Cardiac</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005424" MajorTopicYN="N">Flecainide</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012306" MajorTopicYN="N">Risk</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013599" MajorTopicYN="Y">Systole</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018487" MajorTopicYN="N">Ventricular Dysfunction, Left</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Atrioventricular block</Keyword><Keyword MajorTopicYN="N">Flecainide</Keyword><Keyword MajorTopicYN="N">Left ventricular systolic dysfunction</Keyword><Keyword MajorTopicYN="N">Myocardial infarction</Keyword><Keyword MajorTopicYN="N">Ventricular tachycardia/ventricular fibrillation</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>2</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>5</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>5</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>10</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29782862</ArticleId><ArticleId IdType="doi">10.1016/j.ejphar.2018.05.026</ArticleId><ArticleId IdType="pii">S0014-2999(18)30291-7</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">29782260</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>16</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-9040</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2018</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Kardiologiia</Title><ISOAbbreviation>Kardiologiia</ISOAbbreviation></Journal><ArticleTitle>[Polymorphisms of the SCN10A Gene in Patients With Sick Sinus Syndrome].</ArticleTitle><Pagination><StartPage>53</StartPage><EndPage>59</EndPage><MedlinePgn>53-59</MedlinePgn></Pagination><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">To study association of rs6795970 polymorphism of SCN10A gene with development of idiopathic sick sinus syndrome (ISSS).<AbstractText Label="MATERIALS AND METHODS" NlmCategory="METHODS">We examined 109 patients with ISSS, 59 their healthy 1‑st-, 2‑nd-, and 3‑rd-degree relatives, and 630 controls. Patients with ISSS were divided into subgroups according to gender and clinical variant of the disease. All patients underwent cardiologic examination and molecular genetic testing of DNA.<AbstractText Label="RESULTS" NlmCategory="RESULTS">We revealed significant preponderance of homozygous genotype with rare allele of the studied gene among patients with ISSS compared with control group. In addition, this genotype significantly prevailed among men with SSSU in comparison with the control group.<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Genotype AA of the SCN10A gene is associated with a predisposition to the development of ISSS.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Niculina</LastName><ForeName>S Y</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marilovceva</LastName><ForeName>O V</ForeName><Initials>OV</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chernova</LastName><ForeName>A A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tret'jakova</LastName><ForeName>S S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nikulin</LastName><ForeName>D A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Krasnoyarsk State Medical University named after Prof. V. F. Vojno-Yasenetsky.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maksimov</LastName><ForeName>V N</ForeName><Initials>VN</Initials><AffiliationInfo><Affiliation>Federal State Budgetary Institution, "Research Institute of Therapy and Preventive Medicine" at the Siberian Branch of Russian Academy of Medical Sciences.</Affiliation></AffiliationInfo></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Kardiologiia</MedlineTA><NlmUniqueID>0376351</NlmUniqueID><ISSNLinking>0022-9040</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D062559">NAV1.8 Voltage-Gated Sodium Channel</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C568317">SCN10A protein, human</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D005787" MajorTopicYN="N">Gene Frequency</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005838" MajorTopicYN="N">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D062559" MajorTopicYN="N">NAV1.8 Voltage-Gated Sodium Channel</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012804" MajorTopicYN="Y">Sick Sinus Syndrome</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">SCN10A gene</Keyword><Keyword MajorTopicYN="N">genetic polymorphism</Keyword><Keyword MajorTopicYN="N">sick sinus syndrome</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>5</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29782260</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">29782250</PMID><DateCompleted><Year>2019</Year><Month>05</Month><Day>21</Day></DateCompleted><DateRevised><Year>2019</Year><Month>05</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-9040</ISSN><JournalIssue CitedMedium="Print"><Issue>S2</Issue><PubDate><MedlineDate>2018 SFeb</MedlineDate></PubDate></JournalIssue><Title>Kardiologiia</Title><ISOAbbreviation>Kardiologiia</ISOAbbreviation></Journal><ArticleTitle>[Effect of right ventricular myocardial contractility on the response to cardiac resynchronization therapy].</ArticleTitle><Pagination><StartPage>19</StartPage><EndPage>24</EndPage><MedlinePgn>19-24</MedlinePgn></Pagination><Abstract><AbstractText Label="AIM" NlmCategory="OBJECTIVE">To determine the effect of right ventricular myocardial contractility on the response to cardiac resynchronization therapy (CRT).<AbstractText Label="MATERIALS AND METHODS" NlmCategory="METHODS">The study included 80 patients (49 men, mean age 54±10.5) diagnosed with dilated cardiomyopathy, complete left bundle branch block, and the QRS complex width 146 to 240 ms (183±32 ms). Heart failure was NYHA FC III, ejection fraction (EF) - 30.1±3.8 %, 6‑min walk test - 290.5±64.3 m, and end-diastolic volume (EDV) - 220.7±50.9 ml. 35 patients had permanent atrial fibrillation. All patients received implantable devices for CRT; complete artificial atrioventricular block was formed in patients with atrial fibrillation. LV and right ventricular (RV) contractile function was studied in all patients before and at 12 months of the implantation using equilibrium radionuclide tomoventriculography.<AbstractText Label="RESULTS" NlmCategory="RESULTS">At 12 months, 69 (86.25 %) patients were clinical responders to CRT and 11 (13.75 %) patients did not respond to the treatment. The responders showed positive clinical dynamics; LV EF increased from 30.1±3.8 to 42.8±4.8 % (p≤0.001), LV EDV decreased from 220.7±50.9 to 197.9±47.8 ml (p≤0.005). In non-responders, LV EF increased from 30.1±3.8 to 33.8±3.8 % (p≤0.001) and LV EDV increased from 220.7±50.9 to 227.8±27.8 ml (p≤0.001). All patients were retrospectively divided into two groups: Group 1, CRT responders and Group 2, non-responders. A study using radionuclide methods showed that in Group 1 patients, maximum RV filling velocity increased from 1.8±0.36 to 2.17±0.67 (p≤0.001) and the mean velocity of RV filling for one third of diastole increased from 1±0.28 to 1.32±0.45 (p≤0.001). In Group 2, these parameters were significantly worse by 30 and 60 %, respectively.<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Cardiac resynchronization therapy is more effective in preserved contractility of the right heart, and higher values of maximum RV filling velocity for one third of diastole may serve a prognostic criterium for a beneficial response to CRT.
|
2,334,931 |
Endothelial Progenitor Cells in Heart Failure: an Authentic Expectation for Potential Future Use and a Lack of Universal Definition.
|
Congestive heart failure (CHF) is a prevalent disease (especially among the elderly) with high mortality and morbidity rates. The pathological hallmark of CHF is a loss of cardiomyocytes leading to cardiac fibrosis and dysfunctional cardiac remodeling, which culminates in organ failure. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to maintenance of the integrity of endothelial wall and protect ischemic myocardium through forming new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Despite its potential, little is known about EPCs and their function in CHF. Here, we define EPC and its role in health and CHF, highlighting their contributions as a cornerstone in the maintenance of a healthy endothelium. Thereafter, we explore the behavior and relevance of EPCs in the pathophysiology of CHF, their prognostic importance, and possible utilization of EPCs as therapy for CHF. Lastly, the restrictions surrounding the use of EPCs in clinical practice will be discussed.
|
2,334,932 |
Variation in Interleukin 6 Receptor Gene Associates With Risk of Crohn's Disease and Ulcerative Colitis.
|
Interleukin 6 (IL6) is an inflammatory cytokine; signaling via its receptor (IL6R) is believed to contribute to development of inflammatory bowel diseases (IBD). The single nucleotide polymorphism rs2228145 in IL6R associates with increased levels of soluble IL6R (s-IL6R), as well as reduced IL6R signaling and risk of inflammatory disorders; its effects are similar to those of a therapeutic monoclonal antibody that blocks IL6R signaling. We used the effect of rs2228145 on s-IL6R level as an indirect marker to investigate whether reduced IL6R signaling associates with risk of ulcerative colitis (UC) or Crohn's disease (CD). In a genome-wide meta-analysis of 20,550 patients with CD, 17,647 patients with UC, and more than 40,000 individuals without IBD (controls), we found that rs2228145 (scaled to a 2-fold increase in s-IL6R) was associated with reduced risk of CD (odds ratio 0.876; 95% confidence interval 0.822-0.933; P = .00003) or UC (odds ratio 0.932; 95% confidence interval 0.875-0.996; P = .036). These findings indicate that therapeutics designed to block IL6R signaling might be effective in treatment of IBD.
|
2,334,933 |
Na/K-ATPase signaling mediates miR-29b-3p regulation and cardiac fibrosis formation in mice with chronic kidney disease.
|
The Na/K-ATPase is an important membrane ion transporter and a signaling receptor that is essential for maintaining normal cell function. The current study examined the role of Na/K-ATPase signaling in regulating miR-29b-3p, an anti-fibrotic microRNA, in a mouse chronic kidney disease (CKD) model (5/6th partial nephrectomy or PNx). The results showed that CKD induced significant reduction of miR-29b-3p expression in the heart tissue by activation of Src and NFκB signaling in these animals. To demonstrate the role of Na/K-ATPase signaling, we also performed the PNx surgery on Na/K-ATPase α1 heterozygous (α1+/-) mice, which expresses ~40% less Na/K-ATPase α1 compared to their wild type littermates (WT) and exhibits deficiency in Na/K-ATPase signaling. We found that CKD did not significantly change the miR-29b-3p expression in heart tissue from the α1+/- animals. We also found that CKD failed to activate Src and NFκB signaling in these animals. Using isolated cardiac fibroblasts from α1+/- mice and their WT littermates, we showed that ouabain, a specific Na/K-ATPase ligand, induces decreased miR-29b-3p expression in fibroblasts isolated from WT mice, but had no effect in cells from α1+/- mice. Inhibition of NFκB by Bay11-7082 prevented ouabain-induced miR-29b-3p reduction in WT fibroblasts. To further confirm the in vivo effect of Na/K-ATPase signaling in regulation of miR-29b-3p and cardiac fibrosis in CKD animals, we used pNaKtide, a Src inhibiting peptide derived from the sequence of Na/K-ATPase, to block the activation of Na/K-ATPase signaling. The result showed that pNaKtide injection significantly increased miR-29b-3p expression and mitigated the CKD-induced cardiac fibrosis in these animals. These results clearly demonstrated that Na/K-ATPase signaling is an important mediator in CKD that regulates miR-29b-3p expression and cardiac fibrosis, which provides a novel target for regulation of miR-29b-3p in CKD. We also demonstrate that antagonizing Na/K-ATPase signaling by pNaKtide can reduce organ fibrosis through the stimulation of tissue miR-29b-3p expression.
|
2,334,934 |
Lack of tone in mouse small mesenteric arteries leads to outward remodeling, which can be prevented by prolonged agonist-induced vasoconstriction.
|
Inward remodeling of resistance vessels is an independent risk factor for cardiovascular events. Thus far, the remodeling process remains incompletely elucidated, but the activation level of the vascular smooth muscle cell appears to play a central role. Accordingly, previous data have suggested that an antagonistic and supposedly beneficial response, outward remodeling, may follow prolonged vasodilatation. The present study aimed to determine whether 1) outward remodeling follows 3 days of vessel culture without tone, 2) a similar response can be elicited in a much shorter 4-h timeframe, and, finally, 3) whether a 4-h response can be prevented or reversed by the presence of vasoconstrictors in the medium. Cannulated mouse small mesenteric arteries were organocultured for 3 days in the absence of tone, leading to outward remodeling that continued throughout the culture period. In more acute experiments in which cannulated small mesenteric arteries were maintained in physiological saline without tone for 4 h, we detected a similar outward remodeling that proceeded at a rate several times faster. In the 4-h experimental setting, continuous vasoconstriction to ~50% tone by abluminal application of UTP or norepinephrine + neuropeptide Y prevented outward remodeling but did not cause inward remodeling. Computational modeling was used to simulate and interpret these findings and to derive time constants of the remodeling processes. It is suggested that depriving resistance arteries of activation will lead to eutrophic outward remodeling, which can be prevented by vascular smooth muscle cell activation induced by prolonged vasoconstrictor exposure. NEW & NOTEWORTHY We have established an effective 4-h method for studying outward remodeling in pressurized mouse resistance vessels ex vivo and have determined conditions that block the remodeling response. This allows for investigating the subtle but clinically highly relevant phenomenon of outward remodeling while avoiding both laborious 3-day organoid culture of cannulated vessels and in vivo experiments lasting several weeks.
|
2,334,935 |
The Influence of Binding Site Geometry on Anion-Binding Selectivity: A Case Study of Macrocyclic Receptors Built on the Azulene Skeleton.
|
An understanding of host-guest noncovalent interactions lies at the very heart of supramolecular chemistry. Often a minute change to the structure of a host molecule's binding site can have a dramatic impact on a prospective host-guest binding event, changing the relative selectivity for potential guest molecules. With the overall goal of aiding the rational design of selective and effective receptors for anions, we have studied the influence of small perturbations in binding site geometry for a series of five closely related 20-membered macrocyclic tetra-amide receptors, constructed from two building blocks from a pool of azulene-5,7-bisamide, azulene-1,3-bisamide, and dipicolinic bisamide units. The solid-state structures revealed that the conformational preferences of the free receptors are driven by the inherent preferences of the building blocks, yet in some cases the macrocyclic topology is able to over-ride these to promote pre-organized conformations favorable for anion binding. The solid-state structures of the chloride complexes of these receptors revealed that although all the receptors can adapt to binding to the challenging small Cl<sup>-</sup> guest with all the NH groups, only receptors containing azulene-5,7-bisamide units form short and linear, and therefore strong, hydrogen-bonding interactions. These conclusions are further supported by studies in solution. Although all the receptors showed high affinities toward a series of anions (H<sub>2</sub> PO<sub>4</sub><sup>-</sup> , PhCO<sub>2</sub><sup>-</sup> , Cl<sup>-</sup> , and Br<sup>-</sup> ), even in a highly competitive polar medium (DMSO/25 % MeOH), only receptors containing azulene-5,7-bisamide units exhibited non-inherent selectivity for Cl<sup>-</sup> over PhCO<sub>2</sub><sup>-</sup> , breaking the Hofmeister trend of selectivity. The data presented herein highlight the privileged properties of the azulene-5,7-bisamide building block for binding to chloride anions and provide guidelines for the construction of selective and efficient anion receptors with prospective practical applications.
|
2,334,936 |
Efficacy of 0.5% Hyperbaric Bupivacaine with Dexamethasone versus 0.5% Hyperbaric Bupivacaine alone in Spinal Anaesthesia for Patient Undergoing Lower Abdominal Urological and Lower Limb Orthopedic Surgeries.
|
Spinal anaesthesia with local anaesthetics has limited duration. Different additives have been used to prolong spinal anaesthesia. The aim of this study was to determine the efficacy of adding dexamethasone to bupivacaine in spinal anaesthesia specially whether it would prolong the duration of sensory block/ surgical analgesia and post-operative analgesia/pain free period or not. This randomized, prospective, double-blind, clinical study was conducted in the Department of Anaesthesia, Analgesia and Critical Care of Combined Military Hospital, Chittagong from October 2016 to August 2017. Seventy two (72) adult patients scheduled for lower abdominal urological and lower limb orthopedic surgery under spinal anaesthesia were included. They were divided in two groups; each group comprised 36 patients to receive 20mg 0.5% hyperbaric bupivacaine (Bupivacaine group) or 15mg 0.5% hyperbaric bupivacaine plus 5mg dexamethasone (Bupivacaine-Dexamethasone/case group) intrathecally. The patients were evaluated for quality, quantity and duration of sensory block/surgical analgesia, post-operative analgesia/pain free period, blood pressure, heart rate, nausea, and vomiting or other complications. There were no significant differences in demographic data, sensory level and onset time of the sensory block between two groups. Duration of sensory block/Surgical analgesia in the bupivacaine group was 92.32±8.34 minutes and in the bupivacaine- dexamethasone/case group was 122.11±10.59 minutes which was statistically highly significant (p<0.001). The duration of post-operative analgesia/pain free period was 208.78±41.57 minutes in the bupivacaine group; whereas it was 412.82±71.51 minutes in the bupivacaine-dexamethasone/case group which was also statistically highly significant (p<0.001). The frequency of complications was not different between two groups. This study has shown that the addition of dexamethasone to bupivacaine in spinal anaesthesia significantly improved the duration of sensory block/surgical analgesia as well as post-operative analgesia/pain free period without any complications.
|
2,334,937 |
Digest: Demographic inferences accounting for selection at linked sites†.
|
Complex demography and selection at linked sites can generate spurious signatures of divergent selection. Unfortunately, many attempts at demographic inference consider overly simple models and neglect the effect of selection at linked sites. In this issue, Rougemont and Bernatchez (2018) applied an approximate Bayesian computation (ABC) framework that accounts for indirect selection to reveal a complex history of secondary contacts in Atlantic salmon (Salmo salar) that might explain a high rate of latitudinal clines in this species.
|
2,334,938 |
Detecting epileptic seizure with different feature extracting strategies using robust machine learning classification techniques by applying advance parameter optimization approach.
|
Epilepsy is a neurological disorder produced due to abnormal excitability of neurons in the brain. The research reveals that brain activity is monitored through electroencephalogram (EEG) of patients suffered from seizure to detect the epileptic seizure. The performance of EEG detection based epilepsy require feature extracting strategies. In this research, we have extracted varying features extracting strategies based on time and frequency domain characteristics, nonlinear, wavelet based entropy and few statistical features. A deeper study was undertaken using novel machine learning classifiers by considering multiple factors. The support vector machine kernels are evaluated based on multiclass kernel and box constraint level. Likewise, for K-nearest neighbors (KNN), we computed the different distance metrics, Neighbor weights and Neighbors. Similarly, the decision trees we tuned the paramours based on maximum splits and split criteria and ensemble classifiers are evaluated based on different ensemble methods and learning rate. For training/testing tenfold Cross validation was employed and performance was evaluated in form of TPR, NPR, PPV, accuracy and AUC. In this research, a deeper analysis approach was performed using diverse features extracting strategies using robust machine learning classifiers with more advanced optimal options. Support Vector Machine linear kernel and KNN with City block distance metric give the overall highest accuracy of 99.5% which was higher than using the default parameters for these classifiers. Moreover, highest separation (AUC = 0.9991, 0.9990) were obtained at different kernel scales using SVM. Additionally, the K-nearest neighbors with inverse squared distance weight give higher performance at different Neighbors. Moreover, to distinguish the postictal heart rate oscillations from epileptic ictal subjects, and highest performance of 100% was obtained using different machine learning classifiers.
|
2,334,939 |
Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus.
|
Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.
|
2,334,940 |
Lipid roles in hERG function and interactions with drugs.
|
Human-ether-a-go-go-related channel (hERG) is a voltage gated potassium channel (K<sub>v</sub>11.1) abundantly expressed in heart and brain tissues. In addition to playing an important role in mediation of repolarizing K<sup>+</sup> currents (I<sub>Kr</sub>) in Action Potential (AP), hERG is notorious for its propensity to interact with various medications. The drug-induced block of K<sup>+</sup> currents across hERG channel are strongly associated with dysrhythmic conditions collectively known as drug-induced long-QT-syndrome. The recent availability of the high-resolution Cryo-EM structures for the hERG channel has provided unique opportunity to resolve structural mechanisms involved into the process of voltage-gating of hERG channels, map various roles played by components of ventricular and neuronal membranes and then to connect it to cellular pathways through which diverse chemical compounds might be affecting function of the channel. Specifically, lipids and lipid derivatives such as polyunsaturated fatty acids (PUFAs), ceramides and steroids have been shown to directly interact with the lipid facing amino acids in various K<sub>v</sub> channels including hERG. In this review, possible lipophilic pathways of hERG activators and blockers, together with the existence of fenestration windows and effects of PUFAs, ceramides and steroids are explored throughout different sections. Finally, the interplay between long QT inducing drugs and phospholipidosis is briefly discussed.
|
2,334,941 |
Arrhythmic hazard map for a 3D whole-ventricle model under multiple ion channel block.
|
To date, proposed in silico models for preclinical cardiac safety testing are limited in their predictability and usability. We previously reported a multi-scale heart simulation that accurately predicts arrhythmogenic risk for benchmark drugs.</AbstractText>We created a comprehensive hazard map of drug-induced arrhythmia based on the electrocardiogram (ECG) waveforms simulated under wide range of drug effects using the multi-scale heart simulator described here, implemented with cell models of human cardiac electrophysiology.</AbstractText>A total of 9075 electrocardiograms constitute the five-dimensional hazard map, with coordinates representing the extent of the block of each of the five ionic currents (rapid delayed rectifier potassium current (IKr</sub> ), fast (INa</sub> ) and late (INa,L</sub> ) components of the sodium current, L-type calcium current (ICa,L</sub> ) and slow delayed rectifier current (IKs</sub> )), involved in arrhythmogenesis. Results of the evaluation of arrhythmogenic risk based on this hazard map agreed well with the risk assessments reported in the literature. ECG databases also suggested that the interval between the J-point and the T-wave peak is a superior index of arrhythmogenicity when compared to the QT interval due to its ability to characterize the multi-channel effects compared with QT interval.</AbstractText>Because concentration-dependent effects on electrocardiograms of any drug can be traced on this map based on in vitro current assay data, its arrhythmogenic risk can be evaluated without performing costly and potentially risky human electrophysiological assays. Hence, the map serves as a novel tool for use in pharmaceutical research and development.</AbstractText>© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.</CopyrightInformation>
|
2,334,942 |
Myocardial injury after noncardiac surgery-incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre.
|
Asymptomatic myocardial injury following noncardiac surgery (MINS) is an independent predictor of 30-day mortality and may go unrecognized based on standard diagnostic definition for myocardial infarction (MI). Given lack of published research on MINS in India, our study aims to determine incidence of MINS in patients undergoing noncardiac surgery at our tertiary care hospital, and evaluate the clinical characteristics including 30-day outcome.The prospective observational study included patients >65 years or >45 years with either hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), cerebrovascular accident (CVA), or peripheral arterial disease undergoing noncardiac surgery. MINS was peak troponin level of ≥0.03 ng/dL at 12-hour or 24-hour postoperative. All patients were followed for 30 days postoperatively. Predictors of MINS and mortality were analyzed using multivariate logistic regression. Patients categorized based on peak troponin cut-off values determined by receiver operating characteristic curve were analyzed by Kaplan-Meir test to compare the survival of patients between the groups.Among 1075 patients screened during 34-month period, the incidence of MINS was 17.5% (188/1075). Patients with DM, CAD, or who underwent peripheral nerve block anaesthesia were 1.5 (P < .01), 2 (P < .001), and 12 (P < .001) times, respectively, more likely to develop MINS than others. Patients with heart rates ≥96 bpm before induction of anesthesia were significantly associated with MINS (P = .005) and mortality (P = .02). The 30-day mortality in MINS cohort was 11.7% (22/188, 95% CI 7.5%-17.2%) vs 2.5% (23/887, 95% CI 1.7%-3.9%) in patients without MINS (P < .001). ECG changes (P = .002), peak troponin values >1 ng/mL (P = .01) were significantly associated with mortality. A peak troponin cut-off of >0.152 ng/mL predicted mortality among MINS patients at 72% sensitivity and 58% specificity. Lack of antithrombotic therapy following MINS was independent predictor of mortality (P < .001), with decreased mortality in patients who took post-op ASA (Aspirin) or Clopidogrel. Mortality among MINS patients with post-op ASA intake is 6.7% vs 12.1% among MINS patients without post-op ASA intake. Mortality among MINS patients with post-op Clopidogrel intake is 10.5% vs 11.8% among MINS patients without post-op Clopidogrel intake.A higher (17.5%, 95% CI 15-19%) incidence of MINS was observed in our patient cohort with significant association with 30-day mortality. Serial postoperative monitoring of troponin following noncardiac surgery as standard of care, would identify "at risk" patients translating to improved outcomes.
|
2,334,943 |
Effects of an infratrochlear nerve block on reducing the oculocardiac reflex during strabismus surgery: a randomized controlled trial.
|
To determine whether an infratrochlear nerve block (ITB) can reduce the oculocardiac reflex (OCR) during strabismus surgery on the medial rectus muscle (MR).</AbstractText>This prospective, randomized single-masked study included 60 patients with intermittent exotropia scheduled for unilateral MR resection/lateral rectus recession under general anesthesia. Patients were randomly allocated to receive a regional nerve block of the infratrochlear nerve (ITB group) prior to surgery or standard treatment without a nerve block (control group). The OCR was defined as a sudden decrease in heart rate of ≥ 15% from baseline. Changes in heart rate (HR) and the incidence of the OCR were measured during the three stages of surgery applied to the MR in each group: conjunctival incision, muscle dissection, and muscle traction.</AbstractText>There were no intergroup differences in patient demographics or baseline HR. The mean HRs during conjunctival incision, muscle dissection, and muscle traction were 94, 90, and 96 bpm, respectively, in the ITB group, and 85, 68, and 84 bpm in the control group; the corresponding OCR incidence rates were 3, 20, and 10%; and 7, 87, and 38%. The HR was higher and the OCR incidence was lower in the ITB group than in the control group during muscle dissection and traction (all p < 0.05).</AbstractText>An ITB maintains a stable HR and reduces the OCR during surgery on the MR. The ITB is less invasive and easily accessible to a surgeon, and can help improve the safety of strabismus surgery.</AbstractText>
|
2,334,944 |
In Silico Pharmacoepidemiologic Evaluation of Drug-Induced Cardiovascular Complications Using Combined Classifiers.
|
Drug-induced cardiovascular complications are the most common adverse drug events and account for the withdrawal or severe restrictions on the use of multitudinous postmarketed drugs. In this study, we developed new in silico models for systematic identification of drug-induced cardiovascular complications in drug discovery and postmarketing surveillance. Specifically, we collected drug-induced cardiovascular complications covering the five most common types of cardiovascular outcomes (hypertension, heart block, arrhythmia, cardiac failure, and myocardial infarction) from four publicly available data resources: Comparative Toxicogenomics Database, SIDER, Offsides, and MetaADEDB. Using these databases, we developed a combined classifier framework through integration of five machine-learning algorithms: logistic regression, random forest, k-nearest neighbors, support vector machine, and neural network. The totality of models included 180 single classifiers with area under receiver operating characteristic curves (AUC) ranging from 0.647 to 0.809 on 5-fold cross-validations. To develop the combined classifiers, we then utilized a neural network algorithm to integrate the best four single classifiers for each cardiovascular outcome. The combined classifiers had higher performance with an AUC range from 0.784 to 0.842 compared to single classifiers. Furthermore, we validated our predicted cardiovascular complications for 63 anticancer agents using experimental data from clinical studies, human pluripotent stem cell-derived cardiomyocyte assays, and literature. The success rate of our combined classifiers reached 87%. In conclusion, this study presents powerful in silico tools for systematic risk assessment of drug-induced cardiovascular complications. This tool is relevant not only in early stages of drug discovery but also throughout the life of a drug including clinical trials and postmarketing surveillance.
|
2,334,945 |
Enhanced Exciton and Photon Confinement in Ruddlesden-Popper Perovskite Microplatelets for Highly Stable Low-Threshold Polarized Lasing.
|
At the heart of electrically driven semiconductors lasers lies their gain medium that typically comprises epitaxially grown double heterostuctures or multiple quantum wells. The simultaneous spatial confinement of charge carriers and photons afforded by the smaller bandgaps and higher refractive index of the active layers as compared to the cladding layers in these structures is essential for the optical-gain enhancement favorable for device operation. Emulating these inorganic gain media, superb properties of highly stable low-threshold (as low as ≈8 µJ cm<sup>-2</sup> ) linearly polarized lasing from solution-processed Ruddlesden-Popper (RP) perovskite microplatelets are realized. Detailed investigations using microarea transient spectroscopies together with finite-difference time-domain simulations validate that the mixed lower-dimensional RP perovskites (functioning as cladding layers) within the microplatelets provide both enhanced exciton and photon confinement for the higher-dimensional RP perovskites (functioning as the active gain media). Furthermore, structure-lasing-threshold relationship (i.e., correlating the content of lower-dimensional RP perovskites in a single microplatelet) vital for design and performance optimization is established. Dual-wavelength lasing from these quasi-2D RP perovskite microplatelets can also be achieved. These unique properties distinguish RP perovskite microplatelets as a new family of self-assembled multilayer planar waveguide gain media favorable for developing efficient lasers.
|
2,334,946 |
Efficacy of IANB and Gow-Gates Techniques in Mandibular Molars with Symptomatic Irreversible Pulpitis: A Prospective Randomized Double Blind Clinical Study.
|
The aim of the present study was to compare the efficacy of the inferior alveolar nerve block (IANB) and Gow-Gates techniques in mandibular molars with symptomatic irreversible pulpitis.</AbstractText>In this randomised, double-blind clinical trial, 80 patients referred to Mashhad Dental School, were randomly divided into two groups: IANB and Gow-Gates anaesthetic techniques using 2% lidocaine with 1:100000 epinephrine. After injection, if pain during caries/dentin removal and access cavity preparation was reported in each group, the patients once again were randomly allocated to receive buccal or lingual supplementary infiltration. Pain severity was evaluated using a visual analogue scale. The rates of positive aspiration and changes in heart rate were compared between the IANB and Gow-Gates. Paired and individual t</i>-tests and the Mann-Whitney U</i>-test were used to compare the reduction in pain severity. The level of significance was set at 0.05.</AbstractText>The success rates of anaesthesia in the Gow-Gates and IANB techniques were 50% and 42.5%, respectively with no significant difference (P</i>=0.562). Supplementary infiltrations significantly reduced pain severity in all subgroups (P</i><0.05). Lingual infiltration resulted in a significantly greater reduction in pain severity in the IANB group than in the Gow-Gates group (P</i><0.05). No significant difference in heart rate or positive aspiration results was observed between groups (P</i>>0.05).</AbstractText>In the present study, the efficacy of the IANB and Gow-Gates techniques was comparable in mandibular molars with symptomatic irreversible pulpitis. Supplementary buccal and lingual infiltration significantly reduced pain severity.</AbstractText>
|
2,334,947 |
A Critical Review on Obstetric Follow-up of Women Affected by Systemic Lupus Erythematosus.
|
 To review the existing recommendations on the prenatal care of women with systemic lupus erythematosus (SLE), based on currently available scientific evidence.</AbstractText> An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed), EMBASE and The Cochrane Library databases, using the medical subject headings (MeSH) terms "systemic lupus erythematosus" AND "high-risk pregnancy" OR "prenatal care." Studies published in English between 2007 and 2017 were included; experimental studies and case reports were excluded. In cases of disagreement regarding the inclusion of studies, a third senior researcher was consulted. Forty titles were initially identified; four duplicates were excluded. After reading the abstracts, 7 were further excluded and 29 were selected for a full-text evaluation.</AbstractText> Systemic lupus erythematosus flares, preeclampsia, gestation loss, preterm birth, fetal growth restriction and neonatal lupus syndromes (mainly congenital heart-block) were the major complications described. The multidisciplinary team should adopt a specific monitoring, with particular therapeutic protocols. There are safe and effective drug options that should be prescribed for a good control of SLE activity.</AbstractText> Pregnant women with SLE present an increased risk for maternal complications, pregnancy loss and other adverse outcomes. The disease activity may worsen and, thereby, increase the risk of other maternal-fetal complications. Thus, maintaining an adequate control of disease activity and treating flares quickly should be a central goal during prenatal care.</AbstractText>Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.</CopyrightInformation>
|
2,334,948 |
One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer.
|
The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC).</AbstractText>From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides.</AbstractText>Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found.</AbstractText>The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.</AbstractText>
|
2,334,949 |
Inhibiting IL-2 signaling and the regulatory T-cell pathway using computationally designed peptides.
|
Background Increased serum levels of soluble interleukin-2 (IL-2) receptor alpha (sIL-2Rα) are an indicator of poor prognosis in patients with B-cell non-Hodgkin lymphoma (NHL). By binding to IL-2, sIL-2Rα upregulates Foxp3 expression and induces the development of regulatory T (T<sub>reg</sub>) cells. Methods To inhibit the binding of IL-2 to sIL-2Rα with the goal of suppressing the induction of Foxp3 and decreasing T<sub>reg</sub> cell numbers, we developed peptides by structure-based computational design to disrupt the interaction between IL-2 and sIL-2Rα. Each peptide was screened using an enzyme-linked immunosorbent assay (ELISA), and 10 of 22 peptides showed variable capacity to inhibit IL-2/sIL-2Rα binding. Results We identified a lead candidate peptide, CMD178, which consistently reduced the expression of Foxp3 and STAT5 induced by IL-2/sIL-2Rα signaling. Furthermore, production of cytokines (IL-2/interferon gamma [IFN-γ]) and granules (perforin/granzyme B) was preserved in CD8<sup>+</sup> T cells co-cultured with IL-2-stimulated CD4<sup>+</sup> T cells that had been pretreated with CMD178 compared to CD8<sup>+</sup> cells co-cultured with untreated IL-2-stimulated CD4<sup>+</sup> T cells where it was inhibited. Conclusions We conclude that structure-based peptide design can be used to identify novel peptide inhibitors that block IL-2/sIL-2Rα signaling and inhibit T<sub>reg</sub> cell development. We anticipate that these peptides will have therapeutic potential in B-cell NHL and other malignancies.
|
2,334,950 |
Comparing the Effect of Adding Fentanyl, Sufentanil, and Placebo with Intrathecal Bupivacaine on Duration of Analgesia and Complications of Spinal Anesthesia in Patients Undergoing Cesarean Section.
|
Spinal anesthesia is the method of choice for most elective and emergency Cesarean sections. To increase the duration of anesthesia and improve the quality of analgesia during and after surgery, intrathecal opioids, as adjuvant drugs, are used in combination with local anesthetics.</AbstractText>This was a double-blind clinical trial performed on 99 patients. Women were divided into 3 groups of fentanyl, sufentanil, and placebo. For fentanyl group, 12.5 mg of bupivacaine and 25 micrograms of fentanyl; for sufentanil group, 12.5 mg of bupivacaine and 2.5 micrograms of sufentanil; and for placebo group, 12.5 mg of bupivacaine and a half mL of normal saline were injected in subarachnoid space. The sensory and motor block, hemodynamic status (mean blood pressure and heart rate), and probable complications were assessed.</AbstractText>There was no significant difference between the groups in demographic characteristics. Durations of analgesia were, respectively, 314 ± 42.95, 312.5 ± 34.44, and 116.1 ± 42.24 minutes in the fentanyl, sufentanil, and placebo groups (P = 0.0001). Duration of sensory and motor block was higher in fentanyl and sufentanil groups compared with the placebo group. The highest duration of sensory and motor block was noted in sufentanil group (P = 0.0001). No significant difference was found between the groups in the hemodynamic parameters (P > 0.05). The frequency of itching in the fentanyl group was higher than sufentanil and placebo groups (P = 0.003). Also, shivering was higher in the placebo group compared with other groups (P = 0.036).</AbstractText>According to the results, adding 25 microgram fentanyl or 2.5 microgram sufentanil to intrathecal bupivacaine increased the duration of analgesia and provided hemodynamic stability with no major complication. As administering intrathecal fentanyl had a similar duration of analgesia like sufentanil with faster return of motor block and ambulation, it seems that it is a preferred additive for Cesarean section surgery.</AbstractText>
|
2,334,951 |
Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington's Disease.
|
Huntington's disease (HD) is a dominantly inherited neurological disorder caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). But in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed, impairs other organ systems. Indeed, epidemiological and animal model studies suggest higher incidence of and mortality from heart disease in HD. Here, we show that the protein complex mTORC1 is dysregulated in two HD mouse models through a mechanism that requires intrinsic mHTT expression. Moreover, restoring cardiac mTORC1 activity with constitutively active Rheb prevents mortality and relieves the mHTT-induced block to hypertrophic adaptation to cardiac stress. Finally, we show that chronic mTORC1 dysregulation is due in part to mislocalization of endogenous Rheb. These data provide insight into the increased cardiac-related mortality of HD patients, with cardiac mHTT expression inhibiting mTORC1 activity, limiting heart growth, and decreasing the heart's ability to compensate to chronic stress.
|
2,334,952 |
<i>TAS2R38</i> Predisposition to Bitter Taste Associated with Differential Changes in Vegetable Intake in Response to a Community-Based Dietary Intervention.
|
Although vegetable consumption associates with decreased risk for a variety of diseases, few Americans meet dietary recommendations for vegetable intake. <i>TAS2R38</i> encodes a taste receptor that confers bitter taste sensing from chemicals found in some vegetables. Common polymorphisms in <i>TAS2R38</i> lead to coding substitutions that alter receptor function and result in the loss of bitter taste perception. Our study examined whether bitter taste perception <i>TAS2R38</i> diplotypes associated with vegetable consumption in participants enrolled in either an enhanced or a minimal nutrition counseling intervention. DNA was isolated from the peripheral blood cells of study participants (N = 497) and analyzed for polymorphisms. Vegetable consumption was determined using the Block Fruit and Vegetable screener. We tested for differences in the frequency of vegetable consumption between intervention and genotype groups over time using mixed effects models. Baseline vegetable consumption frequency did not associate with bitter taste diplotypes (<i>P</i> = 0.937), however after six months of the intervention, we observed an interaction between bitter taste diplotypes and time (<i>P</i> = 0.046). Participants in the enhanced intervention increased their vegetable consumption frequency (<i>P</i> = 0.020) and within this intervention group, the bitter non-tasters and intermediate-bitter tasters had the largest increase in vegetable consumption. In contrast, in the minimal intervention group, the bitter tasting participants reported a decrease in vegetable consumption. Bitter-non tasters and intermediate-bitter tasters increased vegetable consumption in either intervention more than those who perceive bitterness. Future precision medicine applications could consider genetic variation in bitter taste perception genes when designing dietary interventions.
|
2,334,953 |
Does Sphenopalatine Ganglion Block Improve Pain Control and Intraoperative Hemodynamics in Children Undergoing Palatoplasty? A Randomized Controlled Trial.
|
Children undergoing cleft palate repair have pain, dysphagia, and wound irritation in the immediate postoperative phase that may compromise surgical outcomes. This trial evaluates the efficacy of the sphenopalatine ganglion block (SPGB) in optimizing intraoperative hemodynamics and postoperative analgesia in children undergoing primary palatoplasty.</AbstractText>The study was designed as a prospective, double-blind, randomized controlled trial comparing the use of SPGB with general anesthesia (GA) (study group) versus the use of only GA (control group). Routine preoperative documentation included type of cleft, patient weight, hemoglobin (Hb%), packed cell volume (PCV), blood pressure, and echocardiogram. Intraoperative monitoring included heart rate, blood pressure, and surgical field assessment. Postoperatively, the pain score, pain-free duration, and need for rescue analgesics were recorded. Postsurgical changes in Hb% and PCV values were assessed. Data analysis of collected variables was performed using SPSS software (version 16; IBM, Armonk, NY). Quantitative data were assessed for normality using the Shapiro-Wilk test and analyzed using the independent-sample t test, and the Fisher exact test was used for comparison of the binary variable (gender). The outcome variables were compared between the study and control groups after adjustment for confounding variables. P < .05 was considered statistically significant.</AbstractText>We randomized 100 patients undergoing primary palatoplasty under GA into the control group (n = 49) and study group (SPGB) (n = 51). Three patients were excluded from the control group because of changes in intraoperative anesthetic protocol. The results showed statistically significant differences in the postsurgical pain-free duration (19.46 minutes vs 87.59 minutes) and mean blood loss (105.5 mL vs 62 mL) in favor of the study group. Surgical field and postoperative reduction of Hb% and PCV were also significantly favorable for the study group.</AbstractText>SPGB is a potent pre-emptive technique offering excellent perioperative analgesia, hemodynamic stability, and a clear surgical field.</AbstractText>Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
|
2,334,954 |
Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.
|
Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO2</sub>).</AbstractText>We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO2</sub>). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg.</AbstractText>Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO2</sub> was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO2</sub> remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01).</AbstractText>In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes.</AbstractText>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation>
|
2,334,955 |
Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.
|
Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease.</AbstractText>In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7-8) and end-of-trial (Weeks 15-16) and was analyzed using available data (no imputation).</AbstractText>Overall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations-analyzed using available data-remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat.</AbstractText>Vadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.</AbstractText>
|
2,334,956 |
Mediators of Behavior Change Maintenance in Physical Activity Interventions for Young and Middle-Aged Adults: A Systematic Review.
|
Regular physical activity is important for maintaining physical and mental health. Benefits are optimized when physical activity is maintained. Understanding causal mechanisms is important to inform future interventions.</AbstractText>To investigate mediators of physical activity maintenance.</AbstractText>Six databases were searched (Medline, EMBASE, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, and Web of Science). Eligibility criteria included adult nonclinical populations, validated measure of physical activity behavior at baseline and at least 6 months postbaseline, control/comparison group(s), and reported mediators of physical activity behavior change. Mediators were examined according to (i) formal mediation tests, (ii) mediator association with physical activity outcome, and (iii) intervention effects on mediators.</AbstractText>There were few formal mediation tests conducted (n = 12/39 included studies), and various other methodological limitations were identified. There was some evidence that effective mediators in formal mediation tests at 6 months and later included the "behavioral processes of change" (n = 5/6). Many of the included interventions were not effective for changing targeted mediators (only 34% of 413 tests of mediator changes were significant).</AbstractText>There were a number of methodological and statistical limitations in the evidence base. In future, prespecified formal mediation tests should be carried out and could be aided by a formal framework. Social and environmental variables should be considered in addition to intrapersonal variables. Improving knowledge of how to change hypothesized mediators, based on theory and evidence, will reveal how physical activity behavior change maintenance can be achieved. Maintenance research would be enhanced by establishing a formal definition of behavior change "maintenance." PROSPERO registration: PROSPERO 2015:CRD- 42015025462.</AbstractText>
|
2,334,957 |
Spread of injectate around hip articular sensory branches of the femoral nerve in cadavers.
|
Anatomical knowledge dictates that regional anaesthesia after total hip arthroplasty requires blockade of the hip articular branches of the femoral and obturator nerves. A direct femoral nerve block increases the risk of fall and impedes mobilisation. We propose a selective nerve block of the hip articular branches of the femoral nerve by an ultrasound-guided injection in the plane between the iliopsoas muscle and the iliofemoral ligament (the iliopsoas plane). The aim of this study was to assess whether dye injected in the iliopsoas plane spreads to all hip articular branches of the femoral nerve.</AbstractText>Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve.</AbstractText>In 10 dissections (67% [95% confidence interval: 38-88%]), the injectate was contained in the iliopsoas plane staining all hip articular branches of the femoral nerve without spread to motor branches. In four dissections (27% [8-55%]), the injection was unintentionally made within the iliopectineal bursa resulting in secondary spread. In one dissection (7% [0.2-32%]) adhesions partially obstructed the spread of dye.</AbstractText>An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could generate a selective sensory nerve block of the articular branches of the femoral nerve without motor blockade.</AbstractText>© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.</CopyrightInformation>
|
2,334,958 |
Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.
|
Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.
|
2,334,959 |
Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells.
|
We report the design, synthesis, and biological evaluation of some potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumors, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229. The design of these molecules was informed and supported by X-ray crystal structures. Compound 1 (EG01377) was identified as having properties suitable for further investigation. Compound 1 was then tested in several in vitro assays and was shown to have antiangiogenic, antimigratory, and antitumor effects. Remarkably, 1 was shown to be selective for NRP1 over the closely related protein NRP2. In purified Nrp1<sup>+</sup>, FoxP3<sup>+</sup>, and CD25<sup>+</sup> populations of Tregs from mice, 1 was able to block a glioma-conditioned medium-induced increase in TGFβ production. This comprehensive characterization of a small-molecule NRP1 antagonist provides the basis for future in vivo studies.
|
2,334,960 |
SIRT3: A New Regulator of Cardiovascular Diseases.
|
Cardiovascular diseases (CVDs) are the leading causes of death worldwide, and defects in mitochondrial function contribute largely to the occurrence of CVDs. Recent studies suggest that sirtuin 3 (SIRT3), the mitochondrial NAD<sup>+</sup>-dependent deacetylase, may regulate mitochondrial function and biosynthetic pathways such as glucose and fatty acid metabolism and the tricarboxylic acid (TCA) cycle, oxidative stress, and apoptosis by reversible protein lysine deacetylation. SIRT3 regulates glucose and lipid metabolism and maintains myocardial ATP levels, which protects the heart from metabolic disturbances. SIRT3 can also protect cardiomyocytes from oxidative stress-mediated cell damage and block the development of cardiac hypertrophy. Recent reports show that SIRT3 is involved in the protection of several heart diseases. This review discusses the progress in SIRT3-related research and the role of SIRT3 in the prevention and treatment of CVDs.
|
2,334,961 |
Clinical effects of single femoral nerve block in combination with general anesthesia on geriatric patients receiving total knee arthroplasty.
|
To evaluate the clinical effects of single femoral nerve block (sFNB) combined with general anesthesia on geriatric patients receiving unilateral total knee arthroplasty (UTKA).</AbstractText>Sixty geriatric UTKA patients who were treated in The First People's Hospital of Changzhou from January 2015 to August 2015 were randomly divided into an sFNB + laryngeal mask airway (FLA) group, an sFNB + tracheal intubation (FGA) group and a tracheal intubation (GA) group. Their clinical parameters and indices were recorded. They were scored by the Visual Analogue Scale (VAS).</AbstractText>All patients completed this study. FLA and FGA groups used less propofol, remifentanil and fentanyl than GA group (P<0.01), with shorter recovery time and extubation time (P<0.05). Compared to GA group, FLA and FGA groups had lower systolic blood pressures at T3, T4 and T5 (P<0.05), and lower heart rates at T5 (P<0.05). FLA and FGA groups had fewer cases of adverse reactions after extubation (P<0.01). FLA group was less prone to irritating cough after extubation and pharyngeal pain than FGA and GA groups (P<0.01). The postoperative six hour and 24 hour VAS scores in resting state as well as the postoperative 24 hour and 48 hour scores in training state of FLA and FGA groups were lower than those of GA group (P<0.05). FLA and FGA groups used significantly lower times and total doses of patient-controlled intravenous analgesia pump.</AbstractText>sFNB combined with general anesthesia, especially that using laryngeal mask, were superior to general anesthesia alone, which reduced recovery and extubation times, and decreased intraoperative and postoperative drug uses, postoperative early VAS score and adverse reactions.</AbstractText>
|
2,334,962 |
Impact of brain arousal and time-on-task on autonomic nervous system activity in the wake-sleep transition.
|
Autonomic nervous system (ANS) activity has been shown to vary with the state of brain arousal. In a previous study, this association of ANS activity with distinct states of brain arousal was demonstrated using 15-min EEG data, but without directly controlling for possible time-on-task effects. In the current study we examine ANS-activity in fine-graded EEG-vigilance stages (indicating states of brain arousal) during two conditions of a 2-h oddball task while controlling for time-on-task. In addition, we analyze the effect of time-on-task on ANS-activity while holding the level of brain arousal constant.</AbstractText>Heart rate and skin conductance level of healthy participants were recorded during a 2-h EEG with eyes closed under simultaneous presentation of stimuli in an ignored (N = 39) and attended (N = 39) oddball condition. EEG-vigilance stages were classified using the Vigilance Algorithm Leipzig (VIGALL 2.1). The time-on-task effect was tested by dividing the EEG into four 30-min consecutive time blocks. ANS-activity was compared between EEG-vigilance stages across the entire 2 h and within each time block.</AbstractText>We found a coherent decline of ANS-activity with declining brain arousal states, over the 2-h recording and in most cases within each 30-min block in both conditions. Furthermore, we found a significant time-on-task effect on heart rate, even when arousal was kept constant. It was most pronounced between the first and all subsequent blocks and could have been a consequence of postural change at the beginning of the experiment.</AbstractText>Our findings contribute to the validation of VIGALL 2.1 using ANS parameters in 2-h EEG recording under oddball conditions.</AbstractText>
|
2,334,963 |
MECP2 mutation in a boy with severe apnea and sick sinus syndrome.
|
Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene, which encodes methyl-CpG-binding protein 2 (MECP2). It almost exclusively affects the female sex and is considered lethal in the male sex. However, an increasing number of male patients with MECP2 mutations have been reported, including patients who suddenly died of unknown causes. We report a case of MECP2 mutation in a male patient who exhibited neonatal encephalopathy. He developed severe apnea, epilepsy, and psychomotor developmental delay and died suddenly of sick sinus syndrome at 17 months of age. Severe bradycardia had been noticed since 16 months of age. His older brother followed a similar clinical course and died at 30 months of age. The brother had also experienced severe bradycardia. This familial case might help to clarify the causes of sudden death in cases of MECP2 mutations.
|
2,334,964 |
Clonidine as an Adjuvant to Caudal Epidural Ropivacaine for Lumbosacral Spine Surgeries.
|
Caudal epidural analgesia is a proven technique for providing analgesia for spinal surgeries. Prolonged pain relief with no motor blockade is desired for early mobilization.</AbstractText>The objective of this study is to compare the effect of adding 1 μg/kg of clonidine to injection ropivacaine 0.2% with respect to duration of analgesia, hemodynamic effects, and associated side effects.</AbstractText>In this prospective double-blind study, a total of 60 patients undergoing lumbosacral spine surgery were randomized to receive 25 cc caudal epidural injection of either injection ropivacaine 0.2% (Group R, n</i> = 30) or a mixture of injection ropivacaine 0.2% and injection clonidine 1 μg/kg (Group RD, n</i> = 30) under general anesthesia after the patient was positioned prone for surgery. Visual analog scale (VAS) scores, heart rate, blood pressures, and time to rescue analgesia and sedation score were recorded at regular intervals for the first 24 h.</AbstractText>Mean VAS scores were significantly lower in the RC Group for up to 12 h following the caudal block. The time to first rescue analgesic was prolonged in the RC group compared to the R Group, and it was statistically significant. No clinically significant hemodynamic changes were noted in either of the groups. No other side effects were seen in both the groups.</AbstractText>These results suggest that injection clonidine is an effective additive to injection ropivacaine for caudal epidural analgesia in lumbosacral spine surgeries.</AbstractText>
|
2,334,965 |
Evaluation of the Hemodynamic Response of Intravenous Clonidine versus Ropivacaine Scalp Block to Insertion of Scalp Pins in Neurosurgical Patients.
|
The application of the skull-pin head-holder, used to stabilize the head during neurosurgical procedures, produces an intense nociceptive stimulus and results in abrupt increases in blood pressure and cerebral blood flow under general anesthesia. Different anesthetic and pharmacologic techniques, including local anesthetics, narcotics, antihypertensives, and deepening of anesthesia with inhalation anesthetics, have been used to blunt this deleterious effect with variable success.</AbstractText>To compare the analgesic and hemodynamic effects of ropivacaine scalp block, and intravenous (IV) clonidine in attenuating the hemodynamic response to the scalp pin insertion in neurosurgical patients.</AbstractText>A comparative two group's clinical study of 64 patients undergoing elective craniotomy in Department of Anaesthesiology, Bangalore Medical College and Research Institute.</AbstractText>Sixty-four patients were allocated into any one of two groups of 32 patients each, by means of computer-generated randomization: (1) Group S: Patients receiving scalp block with injected ropivacaine 0.25% 30 ml. (2) Group C: Patients receiving 2 μg/kg IV clonidine.</AbstractText>Descriptive and inferential statistical analysis has been carried out in the present study. Results on continuous measurements are presented on mean ± standard deviation (minimum-maximum) and results on categorical measurements are presented in number (%). Significance is assessed at 5% level of significance.</AbstractText>Increase in heart rate and blood pressure during pin insertion was attenuated by clonidine hydrochloride (P</i> < 0.001). The number of patients who required more fentanyl and propofol to stabilize the hypertensive response were more in control group than clonidine group.</AbstractText>IV clonidine maximally attenuated the hemodynamic response to application of head pins in a dose of 2 μg/kg compared to ropivacaine scalp block, thus maintaining intracranial pressure for neurosurgical anesthesia.</AbstractText>
|
2,334,966 |
Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task.
|
Associative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning.</AbstractText>We utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: "control-opioid," "pain-opioid," "control-pain," and "opioid-pain." Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task.</AbstractText>HRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, η2</sup>partial</sub> = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, η2</sup>partial</sub> = .16).</AbstractText>Findings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli.</AbstractText>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation>
|
2,334,967 |
Targeting cytokines to treat asthma and chronic obstructive pulmonary disease.
|
Cytokines play a key role in orchestrating and perpetuating the chronic airway inflammation in asthma and chronic obstructive pulmonary disease (COPD), making them attractive targets for treating these disorders. Asthma and some cases of COPD are mainly driven by type 2 immune responses, which comprise increased airway eosinophils, T helper 2 (T<sub>H</sub>2) cells and group 2 innate lymphoid cells (ILC2s) and the secretion of IL-4, IL-5 and IL-13. Clinical trials of antibodies that block these interleukins have shown reduced acute exacerbations and oral corticosteroid use and improvements in lung function and symptoms in selected patients. More recent approaches that block upstream cytokines, such as thymic stromal lymphopoietin (TSLP), show promise in improving patient outcome. Importantly, the clinical trials in cytokine blockade have highlighted the crucial importance of patient selection for the successful use of these expensive therapies and the need for biomarkers to better predict drug responses.
|
2,334,968 |
Agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses under clinical conditions.
|
To determine agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses undergoing elective surgery.</AbstractText>Prospective balanced incomplete block design.</AbstractText>A total of 18 client-owned horses.</AbstractText>Invasive blood pressure (IBP) was measured simultaneously in one of the following three combinations: 1) transverse facial and facial artery; 2) transverse facial and metatarsal artery; and 3) facial and metatarsal artery. The agreement in blood pressure measured for each combination was performed in six horses. At each sample time, systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were measured concurrently in each artery, and the mean of three consecutive measurements was recorded. The position of horse, heart rate and use of dobutamine were also recorded. Bland-Altman analysis was used to assess agreement between sites.</AbstractText>A total of 54 paired measurements were obtained, with 18 paired measurements from each combination. All paired measurements showed poor and haphazard (nonsystematic) agreement. The widest limit of agreement was 51 mmHg for SAP measured in the facial artery and metatarsal artery, with a bias of -11 mmHg. The smallest limit of agreement was 16 mmHg for MAP measured in the transverse facial and metatarsal artery, with a bias of 1 mmHg.</AbstractText>There was poor and haphazard agreement for SAP, MAP and DAP measured in each pair of peripheral arteries in this study. These results show that blood pressure measured in different peripheral arteries cannot be used interchangeably. This has implications for studies that use IBP as an outcome variable and studies determining agreement between noninvasive blood pressure and IBP measurements in horses under general anaesthesia.</AbstractText>Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
|
2,334,969 |
Efficacy and safety of interscalene block combined with general anesthesia for arthroscopic shoulder surgery: A meta-analysis.
|
There is controversy regarding the efficacy and safety of using interscalene block (ISB) combined with general anesthesia (GA) for arthroscopic shoulder surgery. Our meta-analysis was undertaken to evaluate the utility of this approach.</AbstractText>We searched the PubMed, Cochrane Library, EMBASE, CNKI, VIP and ClinicalTrials.gov databases for randomized controlled trials. The primary endpoint was extubation time. Secondary endpoints included intraoperative heart rate, pain scores on the day of and 1 day after the operation, intraoperative systolic blood pressure and adverse events.</AbstractText>Ten RCTs involving 746 patients undergoing arthroscopic shoulder surgery met inclusion criteria. Compared with GA alone, ISB + GA was associated with a shorter extubation time(WMD = -6.13; 95% CI = -8.68 to -3.57; P < 0.00001; I2</sup> = 94%), a lower pain score on the day of the operation (WMD = -2.46; 95% CI = -4.53 to -0.40; P = 0.02; I2</sup> = 97%), a lower pain score 1 day after the operation (WMD = -1.49; 95% CI = -2.46 to -0.52; P = 0.003; I2</sup> = 88%), a lower intraoperative systolic blood pressure (WMD = -12.64; 95% CI = -20.90 to -4.39; P = 0.003; I2</sup> = 95%), a lower heart rate (WMD = -8.81; 95% CI = -15.34 to -2.28; P = 0.008; I2</sup> = 95%) and a lower incidence of adverse events (RR = 0.31; 95% CI = 0.15-0.66; P = 0.002; I2</sup> = 32%).</AbstractText>In patients undergoing arthroscopic shoulder surgery, ISB + GA is associated with a lower heart rate, lower pain scores on the day of and 1 day after the operation, a lower intraoperative systolic blood pressure, a shorter extubation time and a lower incidence of adverse events compared with GA alone.</AbstractText>Copyright © 2018 Elsevier Inc. All rights reserved.</CopyrightInformation>
|
2,334,970 |
Efficacy of virtual block objects in reducing the lung dose in helical tomotherapy planning for cervical oesophageal cancer: a planning study.
|
Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose.</AbstractText>Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes.</AbstractText>The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010).</AbstractText>The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.</AbstractText>
|
2,334,971 |
Effects of Social Exclusion on Cardiovascular and Affective Reactivity to a Socially Evaluative Stressor.
|
Socially disconnected individuals have worse health than those who feel socially connected. The mechanisms through which social disconnection influences physiological and psychological outcomes warrant study. The current study tested whether experimental manipulations of social exclusion, relative to inclusion, influenced subsequent cardiovascular (CV) and affective reactivity to socially evaluative stress.</AbstractText>Young adults (N = 81) were assigned through block randomization to experience either social exclusion or inclusion, using a standardized computer-based task (Cyberball). Immediately after exposure to Cyberball, participants either underwent a socially evaluative stressor or an active control task, based on block randomization. Physiological activity (systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)) and state anxiety were assessed throughout the experiment.</AbstractText>Excluded participants evidenced a significant increase in cardiovascular and affective responses to a socially evaluative stressor. Included participants who underwent the stressor evidenced similar increases in anxiety, but systolic blood pressure, diastolic blood pressure, and heart rate did not change significantly in response to the stressor.</AbstractText>Results contribute to the understanding of physiological consequences of social exclusion. Further investigation is needed to test whether social inclusion can buffer CV stress reactivity, which would carry implications for how positive social factors may protect against the harmful effects of stress.</AbstractText>
|
2,334,972 |
Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT): study protocol for a randomised controlled trial.
|
Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms.</AbstractText><AbstractText Label="METHODS/DESIGN" NlmCategory="METHODS">The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health-related quality of life, severity of post-traumatic stress symptoms and strength of metacognitive beliefs at 4- and 12-month follow-up. Qualitative interviews will help to develop an account of barriers and enablers to the effectiveness of the intervention.</AbstractText>This trial will evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy in alleviating anxiety and depression in cardiac rehabilitation patients. The therapy, if effective, offers the potential to improve psychological wellbeing and quality of life in this large group of patients.</AbstractText>UK Clinical Trials Gateway, ISRCTN74643496 , Registered on 8 April 2015.</AbstractText>
|
2,334,973 |
Modeling and rescue of defective blood-brain barrier function of induced brain microvascular endothelial cells from childhood cerebral adrenoleukodystrophy patients.
|
X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood-brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion. Prior reports have focused on toxic metabolic byproducts and reactive oxygen species as instigators of cerebral inflammation and subsequent immune cell invasion leading to BBB breakdown. This study focuses on the BBB itself and evaluates differences in brain endothelium integrity using cells from ccALD patients and wild-type (WT) controls.</AbstractText>The blood-brain barrier of ccALD patients and WT controls was modeled using directed differentiation of induced pluripotent stem cells (iPSCs) into induced brain microvascular endothelial cells (iBMECs). Immunocytochemistry and PCR confirmed characteristic expression of brain microvascular endothelial cell (BMEC) markers. Barrier properties of iBMECs were measured via trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, and frayed junction analysis. Electron microscopy and RNA-seq were used to further characterize disease-specific differences. Oil-Red-O staining was used to quantify differences in lipid accumulation. To evaluate whether treatment with block copolymers of poly(ethylene oxide) and poly(propylene oxide) (PEO-PPO) could mitigate defective properties, ccALD-iBMECs were treated with PEO-PPO block copolymers and their barrier properties and lipid accumulation levels were quantified.</AbstractText>iBMECs from patients with ccALD had significantly decreased TEER (2592 ± 110 Ω cm2</sup>) compared to WT controls (5001 ± 172 Ω cm2</sup>). They also accumulated lipid droplets to a greater extent than WT-iBMECs. Upon treatment with a PEO-PPO diblock copolymer during the differentiation process, an increase in TEER and a reduction in lipid accumulation were observed for the polymer treated ccALD-iBMECs compared to untreated controls.</AbstractText>The finding that BBB integrity is decreased in ccALD and can be rescued with block copolymers opens the door for the discovery of BBB-specific molecular markers that can indicate the onset of ccALD and has therapeutic implications for preventing the conversion to ccALD.</AbstractText>
|
2,334,974 |
Cardiac Arrest and Death Attributable to the "Diving Response" Triggered During Incision and Debridement of an Abscess of the Forehead.
|
The authors discuss about a patient who, while undergoing a routine procedure to drain a subcutaneous abscess within his forehead, suffered cardiac arrest that we conclude was caused by an activation of the diving response. This reflex affects homeostatic function which alters respiration and preferentially distributes oxygen stores to the heart and brain. Under some conditions, however, this reflex can also trigger cardiovascular collapse and death. The diving reflex is can begin with triggering receptors that are sensitive to cold water, submersion, or pressure within the nasal cavity and other areas supplied by the trigeminal nerve. Studies have shown that this afferent response primarily involves branches of the infraorbital nerve and the anterior ethmoidal nerve. However, other more superior nerves such as those exclusive to the forehead region may also be involved. This study demonstrates for the first time the risks and dangers involved in surgical procedures or manipulation of the trigeminal innervated areas of the human face and in particular the forehead.
|
2,334,975 |
Buccal infiltration versus inferior alveolar nerve block in mandibular 2<sup>nd</sup> premolars with irreversible pulpitis.
|
The purpose of this study is to compare the success rates of inferior alveolar nerve block (IANB) and buccal infiltration anesthesia of mandibular second premolar with irreversible pulpitis and to evaluate the level of patient discomfort with these methods.</AbstractText>Forty patients, who had irreversible pulpitis in the mandibular 2nd</sup> premolar teeth, were included in the study. Patients were randomly distributed in two groups. In one group IANB, in the other group buccal infiltration anesthesia were performed. The efficacy of these two different anesthesia techniques on the related teeth was investigated with the Heft-Parker visual analog scale. In addition, with a pulse oximetry device, the changes in the patients' heart rates were compared between the groups. The obtained data were evaluated statistically.</AbstractText>Both anesthesia techniques reduced the pain significantly in patients before the administration (P < 0.05), but there was no significant difference among the groups regarding the pain control and success rates of anesthesia (P > 0.05). Both of the anesthesia techniques increased the heart rate (P < 0.05). The increase in the heart rate of the patients was significantly higher in the buccal infiltration anesthesia group than the other anesthesia group (P < 0.05).</AbstractText>Within the limitation of this in vivo study, there was no difference between the efficacies of the buccal infiltration anesthesia and IANB anesthesia in the mandibular 2nd</sup> premolar teeth with irreversible pulpitis. Buccal infiltration anesthesia caused more discomfort in the patients compared with the IANB during the administration.</AbstractText>
|
2,334,976 |
Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial.
|
Carditis related to Lyme disease describes inflammation of the tissue of the heart caused by the Lyme bacteria <i>Borrelia burgdorferi sensu lato</i>. It typically presents weeks to months after the bite of an infected tick, which may not be remembered. The most common presentations are due to inflammation of the conduction pathway (electrical pathway) of the heart. This can lead to arrhythmias (abnormal rhythms) and heart block, which can be mild to severe. Symptoms may include dizziness, chest pain and collapse. Inflammation may also occur at other sites such as the pericardium (lining of the heart) and myocardium (heart muscle). In rare cases, carditis can be severe or even fatal. Antibiotic treatment is effective and usually resolves symptoms within 1–4 weeks; however, people with severe Lyme disease will require specialist hospital input until the symptoms recover. There are currently no national guidelines on the management of carditis caused by Lyme disease. Practice may vary between sites, but it would normally include 14–21 days of antibiotic treatment with specialist input where appropriate. Carditis caused by Lyme disease responds well to antibiotic therapy, but if it is left untreated, it can be potentially harmful. Recommendations on this topic will standardise the management of carditis caused by Lyme disease in line with the best available evidence, increase awareness and highlight areas that may be targeted for further research.
|
2,334,977 |
Individual Biometric Identification Using Multi-Cycle Electrocardiographic Waveform Patterns.
|
The electrocardiogram (ECG) waveform conveys information regarding the electrical property of the heart. The patterns vary depending on the individual heart characteristics. ECG features can be potentially used for biometric recognition. This study presents a new method using the entire ECG waveform pattern for matching and demonstrates that the approach can potentially be employed for individual biometric identification. Multi-cycle ECG signals were assessed using an ECG measuring circuit, and three electrodes can be patched on the wrists or fingers for considering various measurements. For biometric identification, our-fold cross validation was used in the experiments for assessing how the results of a statistical analysis will generalize to an independent data set. Four different pattern matching algorithms, i.e., cosine similarity, cross correlation, city block distance, and Euclidean distances, were tested to compare the individual identification performances with a single channel of ECG signal (3-wire ECG). To evaluate the pattern matching for biometric identification, the ECG recordings for each subject were partitioned into training and test set. The suggested method obtained a maximum performance of 89.9% accuracy with two heartbeats of ECG signals measured on the wrist and 93.3% accuracy with three heartbeats for 55 subjects. The performance rate with ECG signals measured on the fingers improved up to 99.3% with two heartbeats and 100% with three heartbeats of signals for 20 subjects.
|
2,334,978 |
Organ recovery cost assessment in the French healthcare system from 2007 to 2014.
|
Organ recovery costs should be assessed to allow efficient and sustainable integration of these costs into national healthcare budgets and policies. These costs are of considerable interest to health economists, hospitals, financial managers and policy makers in most developed countries. This study assessed organ recovery costs from 2007 to 2014 in the French healthcare system based on the national hospital discharge database and a national cost study. The secondary objective was to describe the variability in the population of deceased organ donors during this period.</AbstractText>All stays for organ recovery in French hospitals between January 2007 and December 2014 were quantified from discharge abstracts and valued using a national cost study. Five cost evaluations were conducted to explore all aspects of organ recovery activities. A sensitivity analysis was conducted to test the methodological choice. Trends regarding organ recovery practices were assessed by monitoring indicators.</AbstractText>The analysis included 12 629 brain death donors, with 28 482 organs recovered. The mean cost of a hospital stay was €7469 (SD = €10, 894). The mean costs of separate kidney, liver, pancreas, intestine, heart, lung and heart-lung block recovery regardless of the organs recovered were €1432 (SD = €1342), €502 (SD = €782), €354 (SD = €475), €362 (SD = €1559), €542 (SD = €955), €977 (SD = €1196) and €737 (SD = €637), respectively. Despite a marginal increase in donors, the number of organs recovered increased primarily due to improved practices.</AbstractText>Although cost management is the main challenge for successful organ recovery, other aspects such as organization modalities should be considered to improve organ availability.</AbstractText>
|
2,334,979 |
The effect of spinal hyperbaric bupivacaine-fentanyl or hyperbaric bupivacaine on uterine tone and fetal heart rate in labouring women: a randomised controlled study.
|
The mechanism for fetal heart rate abnormalities following spinal opioids remains controversial. We evaluated uterine tone, using an intra-uterine pressure catheter, and fetal heart rate abnormalities in 30 women in spontaneous labour with cervical dilation of 3-5 cm having combined spinal-epidural analgesia. Women were randomly assigned to receive a spinal with 2.0 mg hyperbaric bupivacaine plus 15 μg fentanyl, or 2.5 mg hyperbaric bupivacaine. The primary outcome measure was an increase > 10 mmHg in baseline uterine tone in the 30-min period following spinal injection. Only three (20%) women who had a bupivacaine-fentanyl spinal showed a > 10 mmHg increase in baseline tone vs. none who had bupivacaine (p = 0.63). The mean (SD) baseline uterine tone after the spinal injection was 13.3 (7.0) mmHg in the bupivacaine-fentanyl group and 7.7 (2.5) mmHg in the bupivacaine group (p = 0.01). Seven (47%) in the bupivacaine-fentanyl group showed new onset fetal heart rate changes during the 30-min period after the spinal, compared with two (13%) in the bupivacaine group (p = 0.04); however, these were transient and responded to intra-uterine resuscitation. Pain scores, sensory and motor block as well as neonatal outcomes were comparable between the groups. We found that raised baseline uterine tone was not more frequent when using bupivacaine-fentanyl rather than bupivacaine in the spinal component of combined spinal-epidural, although absolute values of baseline tone were higher, and fetal heart rate changes more frequent, in the former group.
|
2,334,980 |
Applications of nerve stimulator-guided thoracic paravertebral nerve block plus general anesthesia in small-incision lung cancer surgery.
|
The aim of the study was to investigate the application of nerve stimulator-guided thoracic paravertebral nerve block (TPVB) plus general anesthesia (GA) in small-incision lung cancer surgery.</AbstractText>Forty patients scheduled for small-incision lung cancer surgery, the American Society of Anesthesiologists Grade I-II, were randomized into a TPVB-GA group (Group P) and a GA group (Group G), with 20 cases in each group. The dosage of general anesthetic, mean arterial pressure (MAP) at each time point, and heart rate (HR) of the two groups were recorded. The postoperative respiration recovery time, extubation time, incidence of adverse reactions, and postoperative visual analog scale (VAS) scores of the two groups were also observed.</AbstractText>Group P showed stable hemodynamics, and lower MAP and HR at each time point than Group G (P < 0.05). The intraoperative dosage of general anesthetic in Group P was lower than that in Group G (P < 0.05). The respiration recovery time and extubation time in Group P were significantly shorter than those in Group G (P < 0.05); the incidence of agitation was significantly lower than that in Group G (P < 0.05). The VAS scores of Group P under quiet and cough status were also better than Group G (P < 0.05).</AbstractText>Nerve stimulator-guided TPVB-GA is suitable for small-incision lung cancer surgery.</AbstractText>
|
2,334,981 |
Day-case device implantation-A prospective single-center experience including patient satisfaction data.
|
Many centers perform day-case cardiac rhythm management (CRM) device implantation. However, there is a paucity of prospective data concerning this approach. We performed a prospective single-center study of day-case device implantation, including data on patient satisfaction.</AbstractText>All patients scheduled for a new elective device were considered for a day-case procedure. Exclusion criteria were living alone or without a suitable carer, advancing age/frailty, a metallic valve, and persistent complete heart block. Following discharge, patients were reviewed in device clinic at 6 weeks with an anonymized questionnaire.</AbstractText>During the study period (May 2014-August 2016), 797 new CRM devices were implanted. Of these, 232 were elective and included in the analysis; 101 were planned to be day-case and 131 scheduled for overnight stay. Of the 101 day-case patients, 52 had a pacemaker, 28 an implantable cardioverter defibrillator (ICD), 16 a cardiac resynchronization therapy pacemaker/defibrillator, and five a subcutaneous-ICD. Complications were similar in the day-case (n  =  12, 12%) and overnight stay (n  =  15, 11%) groups (P  =  0.92). In the day-case group, 93 (92%) patients went home the same day. An estimated 111 overnight bed days were saved, translating to a cost saving of £61,912 (euro 70,767, $79,211). Note that 99% (n  =  100) of patients returned the questionnaire. Patient satisfaction was universally high. The majority (n  =  98, 98%) felt ready to go home on discharge; only a minority (n  =  5, 5%) would have preferred an overnight stay.</AbstractText>A significant proportion of elective new CRM device implants can be performed as day-case procedures. With appropriate selection patient acceptability of same-day discharge is high.</AbstractText>© 2018 Wiley Periodicals, Inc.</CopyrightInformation>
|
2,334,982 |
Interatrial block to predict atrial fibrillation in myotonic dystrophy type 1.
|
Paroxysmal atrial fibrillation frequently occurs in Myotonic dystrophy type 1 (DM1) patients. Interatrial block is recognized as predictor of atrial arrhythmias, particularly atrial fibrillation (AF). The aim of this study was to evaluate the role of interatrial block in predicting the onset of atrial fibrillation during 2-year follow-up in DM1 patients who underwent pacemaker implantation for conduction system disorders. The study prospectively enrolled 70 DM1 patients (aged 36-69; 31 M) who underwent pacemaker implantation for cardiac rhythm abnormalities in accordance with the current guidelines. All DM1 patients underwent 12-lead surface ECG, 2D color Doppler echocardiogram and device interrogation at implantation, one month after and every six months thereafter for a minimum of 2-year follow-up. 12-lead surface ECGs were analyzed to diagnose interatrial block (IAB), defined as a P-wave duration ≥120 ms without (partial IAB) or with (advanced IAB) biphasic morphology (±) in the inferior leads. Device interrogation was performed to evaluate the development of new onset atrial high rate electrograms compatible with paroxysmal atrial fibrillation episodes. Interatrial block was detected in 22 patients (31.4%): 18 partial (25.7%) and 4 advanced (5.7%). During follow-up, AF episodes were detected in 18 DM1 patients (25.7%). The study population was divided into 2 groups according to the presence of AF (AF+ Group vs AF- Group). The AF+ Group was older and showed higher prevalence of IAB than the AF- Group. IAB was found to be independent predictor of AF in DM1 population (P < 0.001). A cut-off value of 121 ms for IAB had a sensitivity of 83.3% and specificity of 90.3% in identifying DM1 patients at high risk of developing AF. Interatrial block represents an independent predictor of AF occurrence in our DM1 population with conduction disturbances who had previously undergone pacemaker implantation.
|
2,334,983 |
Effect of Dexmedetomidine Added to Modified Pectoral Block on Postoperative Pain and Stress Response in Patient Undergoing Modified Radical Mastectomy.
|
The most common surgical procedure for breast cancer is the modified radical mastectomy (MRM), but it is associated with significant postoperative pain. Regional anesthesia can reduce the stress response associated with surgical trauma.</AbstractText>Our aim is to explore the efficacy of 1 µg/kg dexmedetomedine added to an ultrasound (US)-modified pectoral (Pecs) block on postoperative pain and stress response in patients undergoing MRM.</AbstractText>A randomized, double-blind, prospective study.</AbstractText>An academic medical center.</AbstractText>Sixty patients with American Society of Anesthesiologists (ASA) physical status I-II (18-60 years old and weighing 50-90 kg) scheduled for MRM were enrolled and randomly assigned into 2 groups (30 in each) to receive a preoperative US Pecs block with 30 mL of 0.25% bupivacaine only (group 1, bupivacaine group [GB]) or 30 mL of 0.25% bupivacaine plus 1 µg/kg dexmedetomidine (group II, dexmedetomidine group [GD]). The patients were followed-up 48 hours postoperatively for vital signs (heart rate [HR], noninvasive blood pressure [NIBP], respiratory rate [RR], and oxygen saturation [Sao2]), visual analog scale (VAS) scores, time to first request of rescue analgesia, total morphine consumption, and side effects. Serum levels of cortisol and prolactin were assessed at baseline and at 1 and 24 hours postoperatively.</AbstractText>A significant reduction in the intraoperative HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) starting at 30 minutes until 120 minutes in the GD group compared to the GB group (P < 0.05) was observed. The VAS scores showed a statistically significant reduction in the GD group compared to the GB group, which started immediately up until 12 hours postoperatively (P < 0.05). There was a delayed time to first request of analgesia in the GD group (25.4 ± 16.4 hrs) compared to the GB group (17 ± 12 hrs) (P = 0.029), and there was a significant decrease of the total amount of morphine consumption in the GD group (9 + 3.6 mg) compared to the GB group (12 + 3.6 mg) (P = 0.001). There was a significant reduction in the mean serum cortisol and prolactin levels at 1 and 24 hours postoperative in the GD patients compared to the GB patients (P < 0.05).</AbstractText>This study was limited by its sample size.</AbstractText>The addition of 1 µg/kg dexmedetomidine to an US-modified Pecs block has superior analgesia and more attenuation to stress hormone levels without serious side effects, compared to a regular Pecs block in patients who underwent MRM.</AbstractText>Postoperative pain, dexmedetomidine, Pecs block, stress response, breast surgery.</AbstractText>
|
2,334,984 |
Avoidance and escape: Defensive reactivity and trait anxiety.
|
Although avoidance and escape behaviors each contribute to maintaining anxiety disorders, only avoidance completely eliminates exposure to the aversive context. Current research compared anticipatory defensive engagement when aversion could either be completely avoided or escaped after initial exposure; in addition, this research examined the impact of trait anxiety on coping-related defensive engagement. Cues signaled that upcoming rapid action would avoid (block), escape (terminate), or not affect subsequent aversive exposure; the acoustic startle reflex was measured during each anticipatory interval to index defensive engagement, and blink magnitudes were compared across low-, moderate-, and high-anxious individuals. For all participants, startle was potentiated when aversive exposure was uncontrollable and attenuated when aversion was avoidable. On escape trials, on the other hand, startle potentiation increased with rising participant anxiety. Results suggest 1) defensive engagement is generally reduced in avoidance contexts relative to contexts in which exposure is certain, and; 2) trait anxiety increases defensive engagement specifically when aversive exposure can be controlled but remains certain.
|
2,334,985 |
In Silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk.
|
Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue. Multiple channel-drug interactions and state-of-the-art human ventricular action potential models ( O'Hara , T. , PLos Comput. Biol. 2011 , 7 , e1002061 ) were used in our simulations. Specifically, 206.766 cellular and 7072 tissue simulations were performed by blocking the slow and the fast components of the delayed rectifier current ( I<sub>Ks</sub> and I<sub>Kr</sub>, respectively) and the L-type calcium current ( I<sub>CaL</sub>) at different levels. The performance of our system was validated by classifying the proarrhythmic risk of 84 compounds, 40 of which present torsadogenic properties. On the basis of these results, we propose the use of a new index (Tx) for discriminating torsadogenic compounds, defined as the ratio of the drug concentrations producing 10% prolongation of the cellular endocardial, midmyocardial, and epicardial APDs and the QT interval, over the maximum effective free therapeutic plasma concentration (EFTPC). Our results show that the Tx index outperforms standard methods for early identification of torsadogenic compounds. Indeed, for the analyzed compounds, the Tx tests accuracy was in the range of 87-88% compared with a 73% accuracy of the hERG IC<sub>50</sub> based test.
|
2,334,986 |
Structural implications of hERG K<sup>+</sup> channel block by a high-affinity minimally structured blocker.
|
Cardiac potassium channels encoded by human ether-à-go-go-related gene (<i>hERG</i>) are major targets for structurally diverse drugs associated with acquired long QT syndrome. This study characterized hERG channel inhibition by a minimally structured high-affinity hERG inhibitor, Cavalli-2, composed of three phenyl groups linked by polymethylene spacers around a central amino group, chosen to probe the spatial arrangement of side chain groups in the high-affinity drug-binding site of the hERG pore. hERG current (<i>I</i><sub>hERG</sub>) recorded at physiological temperature from HEK293 cells was inhibited with an IC<sub>50</sub> of 35.6 nm with time and voltage dependence characteristic of blockade contingent upon channel gating. Potency of Cavalli-2 action was markedly reduced for attenuated inactivation mutants located near (S620T; 54-fold) and remote from (N588K; 15-fold) the channel pore. The S6 Y652A and F656A mutations decreased inhibitory potency 17- and 75-fold, respectively, whereas T623A and S624A at the base of the selectivity filter also decreased potency (16- and 7-fold, respectively). The S5 helix F557L mutation decreased potency 10-fold, and both F557L and Y652A mutations eliminated voltage dependence of inhibition. Computational docking using the recent cryo-EM structure of an open channel hERG construct could only partially recapitulate experimental data, and the high dependence of Cavalli-2 block on Phe-656 is not readily explainable in that structure. A small clockwise rotation of the inner (S6) helix of the hERG pore from its configuration in the cryo-EM structure may be required to optimize Phe-656 side chain orientations compatible with high-affinity block.
|
2,334,987 |
Robust QRS detection for HRV estimation from compressively sensed ECG measurements for remote health-monitoring systems.
|
To present a new compressive sensing (CS)-based method for the acquisition of ECG signals and for robust estimation of heart-rate variability (HRV) parameters from compressively sensed measurements with high compression ratio.</AbstractText>CS is used in the biosensor to compress the ECG signal. Estimation of the locations of QRS segments is carried out by applying two algorithms on the compressed measurements. The first algorithm reconstructs the ECG signal by enforcing a block-sparse structure on the first-order difference of the signal, so the transient QRS segments are significantly emphasized on the first-order difference of the signal. Multiple block-divisions of the signals are carried out with various block lengths, and multiple reconstructed signals are combined to enhance the robustness of the localization of the QRS segments. The second algorithm removes errors in the locations of QRS segments by applying low-pass filtering and morphological operations.</AbstractText>The proposed CS-based method is found to be effective for the reconstruction of ECG signals by enforcing transient QRS structures on the first-order difference of the signal. It is demonstrated to be robust not only to high compression ratio but also to various artefacts present in ECG signals acquired by using on-body wireless sensors. HRV parameters computed by using the QRS locations estimated from the signals reconstructed with a compression ratio as high as 90% are comparable with that computed by using QRS locations estimated by using the Pan-Tompkins algorithm.</AbstractText>The proposed method is useful for the realization of long-term HRV monitoring systems by using CS-based low-power wireless on-body biosensors.</AbstractText>
|
2,334,988 |
Cooperative recruitment of Yan via a high-affinity ETS supersite organizes repression to confer specificity and robustness to cardiac cell fate specification.
|
<i>Cis</i>-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the <i>cis</i>-regulatory logic of a tissue-specific CRM responsible for <i>even-skipped</i> (<i>eve</i>) induction during cardiogenesis organizes the competing inputs of two E-twenty-six (ETS) members: the activator Pointed (Pnt) and the repressor Yan. Using a combination of reporter gene assays and CRISPR-Cas9 gene editing, we suggest that Yan and Pnt have distinct syntax preferences. Not only does Yan prefer high-affinity sites, but an overlapping pair of such sites is necessary and sufficient for Yan to tune Eve expression levels in newly specified cardioblasts and block ectopic Eve induction and cell fate specification in surrounding progenitors. Mechanistically, the efficient Yan recruitment promoted by this high-affinity ETS supersite not only biases Yan-Pnt competition at the specific CRM but also organizes Yan-repressive complexes in three dimensions across the <i>eve</i> locus. Taken together, our results uncover a novel mechanism by which differential interpretation of CRM syntax by a competing repressor-activator pair can confer both specificity and robustness to developmental transitions.
|
2,334,989 |
Task-induced deactivation in diverse brain systems correlates with interindividual differences in distinct autonomic indices.
|
Neuroimaging research has shown that different cognitive tasks induce relatively specific activation patterns, as well as less task-specific deactivation patterns. Here we examined whether individual differences in Autonomic Nervous System (ANS) activity during task performance correlate with the magnitude of task-induced deactivation. In an fMRI study, participants performed a continuous mental arithmetic task in a task/rest block design, while undergoing combined fMRI and heart/respiration rate acquisitions using photoplethysmograph and respiration belt. As expected, task performance increased heart-rate and reduced the RMSSD, a cardiac index related to vagal tone. Across participants, higher heart rate during task was linked to increased activation in fronto-parietal regions, as well as to stronger deactivation in ventromedial prefrontal regions. Respiration frequency during task was associated with similar patterns, but in different regions than those identified for heart-rate. Finally, in a large set of regions, almost exclusively limited to the Default Mode Network, lower RMSSD was associated with greater deactivation, and furthermore, the vast majority of these regions were task-deactivated at the group level. Together, our findings show that inter-individual differences in ANS activity are strongly linked to task-induced deactivation. Importantly, our findings suggest that deactivation is a multifaceted construct potentially linked to ANS control, because distinct ANS measures correlate with deactivation in different regions. We discuss the implications for current theories of cortical control of the ANS and for accounts of deactivation, with particular reference to studies documenting a "failure to deactivate" in multiple clinical states.
|
2,334,990 |
Chinese translation and psychometric testing of the cardiac self-efficacy scale in patients with coronary heart disease in mainland China.
|
A person's self-efficacy plays a critical role during the chronic management process of a health condition. Assessment of self-efficacy for patients with heart diseases is essential for healthcare professionals to provide tailored interventions to help patient to manage the disease.</AbstractText>To translate and test the psychometric properties of the Chinese version of Cardiac Self-efficacy Scale (C-CSES) as a disease-specific instrument for patients with coronary heart disease (CHD) in mainland China.</AbstractText>The original English version of the CSES was translated into Chinese using a forward-backward translation approach. A convenience sample consisting of 224 Chinese patients with CHD were recruited from a university-affiliated hospital in Shiyan, China. The C-CSES and the General Self-efficacy Scale (GSES) were used in this study. The factor structure, convergent and discriminative validities, and internal consistency of the C-CSES were evaluated.</AbstractText>The confirmatory factor analysis (CFA) supported a three-factor high-order structure of the C-CSES with model fit indexes (RMSEA = 0.084, CFI = 0.954, NNFI = 0.927, IFI = 0.954 and χ 2</sup> /df = 2.572). The C-CSES has good internal consistency with a Cronbach's alpha of 0.926. The convergent validity of the C-CSES was established with significantly moderate correlations between the C-CSES and the Chinese version of the GSES (p < 0.001). The C-CSES has also shown good discriminative validity with significant differences of cardiac self-efficacy being found between patients with and without comorbidities of hypertension, diabetes, or heart failure.</AbstractText>The empirical data supported that the C-CSES is a valid and reliable disease-specific instrument for assessing the self-efficacy of Chinese patients with CHD.</AbstractText>
|
2,334,991 |
Cardiac electrophysiological adaptations in the equine athlete-Restitution analysis of electrocardiographic features.
|
Exercising horses uniquely accommodate 7-8-fold increases in heart rate (HR). The present experiments for the first time analysed the related adaptations in action potential (AP) restitution properties recorded by in vivo telemetric electrocardiography from Thoroughbred horses. The horses were subjected to a period of acceleration from walk to canter. The QRS durations, and QT and TQ intervals yielded AP conduction velocities, AP durations (APDs) and diastolic intervals respectively. From these, indices of active, λ = QT/(QRS duration), and resting, λ0 = TQ/(QRS duration), AP wavelengths were calculated. Critical values of QT and TQ intervals, and of λ and λ0 at which plots of these respective pairs of functions showed unity slope, were obtained. These were reduced by 38.9±2.7% and 86.2±1.8%, and 34.1±3.3% and 85.9±1.2%, relative to their resting values respectively. The changes in λ were attributable to falls in QT interval rather than QRS duration. These findings both suggested large differences between the corresponding critical (129.1±10.8 or 117.4±5.6 bpm respectively) and baseline HRs (32.9±2.1 (n = 7) bpm). These restitution analyses thus separately identified concordant parameters whose adaptations ensure the wide range of HRs over which electrophysiological activation takes place in an absence of heart block or arrhythmias in equine hearts. Since the horse is amenable to this in vivo electrophysiological analysis and displays a unique wide range of heart rates, it could be a novel cardiac electrophysiology animal model for the study of sudden cardiac death in human athletes.
|
2,334,992 |
New kids on the block in the ECMC and opportunities 
for early career members in 2018.
|
<b>Opportunities for early career members to get involved in ERS activities in 2018</b> 
http://ow.ly/rmyd30hDBCN.
|
2,334,993 |
Detection of multipoint pulse waves and dynamic 3D pulse shape of the radial artery based on binocular vision theory.
|
Pulse signals contain a wealth of human physiological and pathological information. How to get full pulse information is especially challenging, and most of the traditional pulse sensors can only get the pulse wave of a single point. This study is aimed at developing a binocular pulse detection system and method to obtain multipoint pulse waves and dynamic three-dimensional pulse shape of the radial artery.</AbstractText>The proposed pulse detection approach is image-based and implemented by two steps. First, a new binocular pulse detection system is developed based on the principle of pulse feeling used in traditional Chinese medicine. Second, pulse detection is achieved based on theories and methods of binocular vision and digital image processing. In detail, the sequences of pulse images collected by the designed system as experimental data are sequentially processed by median filtering, block binarization and inversion, area filtering, centroids extraction of connected regions, to extract the pattern centroids as feature points. Then stereo matching is realized by a proposed algorithm based on Gong-shape scan detection. After multipoint spatial coordinate calculation, dynamic three-dimensional reconstruction of the thin film shape is completed by linear interpolation. And then the three-dimensional pulse shape is achieved by finding an appropriate reference time. Meanwhile, extraction of multipoint pulse waves of the radial artery is accomplished by using a suitable reference origin. The proposed method is analyzed from three aspects, which are pulse amplitude, pulse rate and pulse shape, and compared with other detection methods.</AbstractText>Analysis of the results shows that the values of pulse amplitude and pulse rate are consistent with the characteristics of pulse wave of the radial artery, and pulse shape can correctly present the shape of pulse in space and its change trend in time. The comparison results with the other two previously proposed methods further verify the correctness of the presented method.</AbstractText>The designed binocular pulse detection system and proposed algorithm can effectively detect pulse information. This tactile visualization-based pulse detection method has important scientific significance and broad application prospects and will promote further development of objective pulse diagnosis.</AbstractText>Copyright © 2017 Elsevier B.V. All rights reserved.</CopyrightInformation>
|
2,334,994 |
Three-dimensional reconstruction of the intercalated disc including the intercellular junctions by applying volume scanning electron microscopy.
|
The intercalated disc (ID) contains different kinds of intercellular junctions: gap junctions (GJs), desmosomes and areae compositae, essential for adhesion and communication between adjacent cardiomyocytes. The junctions can be identified based on their morphology when imaged using transmission electron microscopy (TEM), however, only with very limited information in the z-dimension. The application of volume EM techniques can give insight into the three-dimensional (3-D) organization of complex biological structures. In this study, we generated 3-D datasets using serial block-face scanning electron microscopy (SBF-SEM) and focused ion beam SEM (FIB-SEM), the latter resulting in datasets with 5 nm isotropic voxels. We visualized cardiomyocytes in murine ventricular heart tissue and, for the first time, we could three-dimensionally reconstruct the ID including desmosomes and GJs with 5 nm precision in a large volume. Results show in three dimensions a highly folded structure of the ID, with the presence of GJs and desmosomes in both plicae and interplicae regions. We observed close contact of GJs with mitochondria and a variable spatial distribution of the junctions. Based on measurements of the shape of the intercellular junctions in 3-D, it is seen that GJs and desmosomes vary in size, depending on the region within the ID. This demonstrates that volume EM is essential to visualize morphological changes and its potential to quantitatively determine structural changes between normal and pathological conditions, e.g., cardiomyopathies.
|
2,334,995 |
Autoregulation of von Willebrand factor function by a disulfide bond switch.
|
Force-dependent binding of platelet glycoprotein Ib (GPIb) receptors to plasma von Willebrand factor (VWF) plays a key role in hemostasis and thrombosis. Previous studies have suggested that VWF activation requires force-induced exposure of the GPIb binding site in the A1 domain that is autoinhibited by the neighboring A2 domain. However, the biochemical basis of this "mechanopresentation" remains elusive. From a combination of protein chemical, biophysical, and functional studies, we find that the autoinhibition is controlled by the redox state of an unusual disulfide bond near the carboxyl terminus of the A2 domain that links adjacent cysteine residues to form an eight-membered ring. Only when the bond is cleaved does the A2 domain bind to the A1 domain and block platelet GPIb binding. Molecular dynamics simulations indicate that cleavage of the disulfide bond modifies the structure and molecular stresses of the A2 domain in a long-range allosteric manner, which provides a structural explanation for redox control of the autoinhibition. Significantly, the A2 disulfide bond is cleaved in ~75% of VWF subunits in healthy human donor plasma but in just ~25% of plasma VWF subunits from heart failure patients who have received extracorporeal membrane oxygenation support. This suggests that the majority of plasma VWF binding sites for platelet GPIb are autoinhibited in healthy donors but are mostly available in heart failure patients. These findings demonstrate that a disulfide bond switch regulates mechanopresentation of VWF.
|
2,334,996 |
Effects of refractory gradients and ablation on fibrillatory activity.
|
The mechanisms involved in onset, maintenance, and termination of atrial fibrillation are not well understood. A biophysical model could be useful to determine how the events unfold.</AbstractText>A two-dimensional cellular automaton consisting of 576 × 576 grid nodes was implemented to demonstrate the types of electrical activity that may occur in compromised atrial substrate. Electrical activation between nodes was made anisotropic (2:1), and the refractory period (RP) was adjusted from 74 to 192 ms in the spatial domain. Presence of collagen fibers were simulated as short lines of conduction block at many random grid sites, while ablation lesions were delineated as longer lines of block. An S1-S2 pulse from one grid corner was utilized to initiate simulated electrical activity. Simulations were done in which 1. no ablation lines, 2. random ablation lines, and 3. parallel ablation lines were added to the grid to determine how this affected the formation and annihilation of rotational activity after S1-S2 stimulation.</AbstractText>As the premature (S2) wavefront traversed the grid, rotational activity formed near boundaries where wavefronts propagated from shorter to longer refractory regions, causing unidirectional block, and were anchored by fiber clusters. Multiple wavelets appeared when wavefronts originating from different driving rotational features collided, and/or by their encounter with RP discontinuities. With the addition of randomly orientated simulated ablation lesions, followed by reinduction of fibrillatory activity, mean activation interval (AI) prolonged from a baseline level of 144.2 ms-160.3 ms (p < 0.001 in most comparisons). During fibrillatory activity, when parallel ablation lines were added to short RP regions, AI prolonged to 150.4 ms (p < 0.001), and when added to long RP regions, AI prolonged to 185.3 ms (p < 0.001). In all cases, AI prolongation after simulated ablation resulted from reduced number and/or from the isolation of local drivers, so that distant drivers in short RP regions activated long RP regions N:1, while distant drivers in long RP regions activated short RP regions at a relatively slow rate.</AbstractText>An automaton model was found useful to generate and test hypotheses concerning fibrillatory activity, which can then be validated in the clinical electrophysiology laboratory.</AbstractText>Copyright © 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
|
2,334,997 |
Case of an Intracranial Malignant Peripheral Nerve Sheath Tumor in the Setting of Pacer-dependent Heart Block.
|
Intracranial malignant peripheral nerve sheath tumors (MPNSTs) are an extremely rare entity with only a handful of cases reported in the literature. MPNSTs typically occur in the extremities and the trunk. The treatment algorithm includes, when possible, gross-total resection as these tumors are extremely aggressive. When these tumors occur intracranially, they are termed malignant intracerebral nerve sheath tumors. The diagnosis hinges on immunohistochemistry and pathological features and often the diagnosis can be delayed for this reason. In this setting, it is critical to utilize intraoperative navigation, thus necessitating the use of fine-cut magnetic resonance imaging (MRI). This report presents a patient who presented with symptoms of obstructive hydrocephalus secondary to an intracranial mass. The patient underwent a full and extensive metastatic workup that was ultimately negative. To complicate things, the patient was fully pacemaker dependent. In this report, we review the literature surrounding this type of tumor, along with a detailed presentation of the case mentioned including the difficulties of cardiac pacing in the setting of MRI.
|
2,334,998 |
AMModels: An R package for storing models, data, and metadata to facilitate adaptive management.
|
Agencies are increasingly called upon to implement their natural resource management programs within an adaptive management (AM) framework. This article provides the background and motivation for the R package, AMModels. AMModels was developed under R version 3.2.2. The overall goal of AMModels is simple: To codify knowledge in the form of models and to store it, along with models generated from numerous analyses and datasets that may come our way, so that it can be used or recalled in the future. AMModels facilitates this process by storing all models and datasets in a single object that can be saved to an .RData file and routinely augmented to track changes in knowledge through time. Through this process, AMModels allows the capture, development, sharing, and use of knowledge that may help organizations achieve their mission. While AMModels was designed to facilitate adaptive management, its utility is far more general. Many R packages exist for creating and summarizing models, but to our knowledge, AMModels is the only package dedicated not to the mechanics of analysis but to organizing analysis inputs, analysis outputs, and preserving descriptive metadata. We anticipate that this package will assist users hoping to preserve the key elements of an analysis so they may be more confidently revisited at a later date.
|
2,334,999 |
Acute Effect of Intermittent Exercise and Action-Based Video Game Breaks on Math Performance in Preadolescent Children.
|
The purpose of this study was to compare the acute effects of video game breaks and intermittent exercise breaks, performed at varying intensities, on math performance in preadolescent children.</AbstractText>A total of 39 children (18 males and 21 females; aged 7-11 y) completed 4 experimental conditions in random order: 8 hours of sitting interrupted with 20 two-minute low-, moderate-, or high-intensity exercise breaks or 20 two-minute sedentary computer game breaks. The intensity of exercise breaks for the low-, moderate-, and high-intensity conditions corresponded with 25%, 50%, and 75% of heart rate reserve, respectively. Math performance was assessed 3 times throughout each condition day using a 90-second math test consisting of 40 single-digit addition and subtraction questions.</AbstractText>There were no significant differences in percent change in math scores (correct answers out of attempted) by condition [low: -1.3 (0.8), moderate: 0.1 (1.3), high: -1.8 (0.7), and computer: -2.5 (0.8); P > .05]. There were significant differences in percent change in math scores over the course of the condition days with lower math scores reported at end-of-day test compared with midday test [-2.4 (0.5) vs -0.4 (0.3); P = .01]. There were no significant condition × time, time × age, condition × age, or condition × time × age interactions (all Ps > .05).</AbstractText>Action-based video game and exercise breaks elicit the same level of math performance in children; however, time of day may impact this relationship. These findings may have important implications for instructional time in elementary classrooms.</AbstractText>
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.