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2,335,000 |
Development and reliability of a streetscape observation instrument for international use: MAPS-global.
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Relationships between several built environment factors and physical activity and walking behavior are well established, but internationally-comparable built environment measures are lacking. The Microscale Audit of Pedestrian Streetscapes (MAPS)-Global is an observational measure of detailed streetscape features relevant to physical activity that was developed for international use. This study examined the inter-observer reliability of the instrument in five countries.</AbstractText>MAPS-Global was developed by compiling concepts and items from eight environmental measures relevant to walking and bicycling. Inter-rater reliability data were collected in neighborhoods selected to vary on geographic information system (GIS)-derived macro-level walkability in five countries (Australia, Belgium, Brazil, Hong Kong-China, and Spain). MAPS-Global assessments (n = 325) were completed in person along a ≥ 0.25 mile route from a residence toward a non-residential destination, and a commercial block was also rated for each residence (n = 82). Two raters in each country rated each route independently. A tiered scoring system was created that summarized items at multiple levels of aggregation, and positive and negative valence scores were created based on the expected effect on physical activity. The intraclass correlation coefficient (ICC) was computed for scales and selected items using one-way random models.</AbstractText>Overall, 86.6% of individual items and single item indicators showed excellent agreement (ICC ≥ 0.75), and 13.4% showed good agreement (ICC = 0.60-0.74). All subscales and overall summary scores showed excellent agreement. Six of 123 items were too rare to compute the ICC. The median ICC for items and scales was 0.92 with a range of 0.50-1.0. Aesthetics and social characteristics showed lower ICCs than other sub-scales, but reliabilities were still in the excellent range (ICC ≥ 0.75).</AbstractText>Evaluation of inter-observer reliability of MAPS-Global across five countries indicated all items and scales had "good" or "excellent" reliability. The results demonstrate that trained observers from multiple countries were able to reliably conduct observations of both residential and commercial areas with the new MAPS-Global instrument. Next steps are to evaluate construct validity in relation to physical activity in multiple countries and gain experience with using MAPS-Global for research and practice applications.</AbstractText>
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2,335,001 |
Ultrasound-Guided Intercostal Nerve Block Following Esophagectomy for Acute Postoperative Pain Relief in the Postanesthesia Care Unit.
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To explore the feasibility, effectiveness, and safety of ultrasound-guided intercostal nerve block (ICNB) for immediate relief of moderate and severe pain following esophagectomy in a postanesthesia care unit (PACU).</AbstractText>Eighty-one patients who complained of moderate to severe pain on arrival to the PACU after an Ivor Lewis esophagectomy were randomly assigned to 2 groups: a sufentanil treatment group (Group A, n = 41) and an intercostal nerve block treatment group (Group B, n = 40). The visual analog scale (VAS) pain scores at rest and on cough at 1, 2, 4, 12, 24, and 48 hours after treatment were monitored. The heart rate, blood pressure, and pulse oxygen saturation (SpO2</sub> ) 2 hours after treatment and the patients' length of stay in the PACU after treatment were recorded. Patient-controlled intravenous analgesia consumption and the incidence of nausea, vomiting, and other adverse reactions were also recorded.</AbstractText>Ultrasound-guided ICNB was performed successfully in all patients in Group B without puncture-related complications. The VAS pain scores at rest and on cough at 1, 2, and 4 hours after treatment in Group B were significantly lower than those in Group A (P < 0.05). The consumption of sufentanil and the incidence of nausea and vomiting were significantly decreased in Group B compared with those in Group A.</AbstractText>Ultrasound-guided ICNB could provide effective and safe pain relief for patients who suffer from moderate to severe pain (VAS score ≥ 5) after esophagectomy in the PACU.</AbstractText>© 2018 World Institute of Pain.</CopyrightInformation>
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2,335,002 |
An automated workflow for segmenting single adult cardiac cells from large-volume serial block-face scanning electron microscopy data.
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This paper presents a new algorithm to automatically segment the myofibrils, mitochondria and nuclei within single adult cardiac cells that are part of a large serial-block-face scanning electron microscopy (SBF-SEM) dataset. The algorithm only requires a set of manually drawn contours that roughly demarcate the cell boundary at routine slice intervals (every 50th, for example). The algorithm correctly classified pixels within the single cell with 97% accuracy when compared to manual segmentations. One entire cell and the partial volumes of two cells were segmented. Analysis of segmentations within these cells showed that myofibrils and mitochondria occupied 47.5% and 51.6% on average respectively, while the nuclei occupy 0.7% of the cell for which the entire volume was captured in the SBF-SEM dataset. Mitochondria clustering increased at the periphery of the nucleus region and branching points of the cardiac cell. The segmentations also showed high area fraction of mitochondria (up to 70% of the 2D image slice) in the sub-sarcolemmal region, whilst it was closer to 50% in the intermyofibrillar space. We finally demonstrate that our segmentations can be turned into 3D finite element meshes for cardiac cell computational physiology studies. We offer our large dataset and MATLAB implementation of the algorithm for research use at www.github.com/CellSMB/sbfsem-cardiac-cell-segmenter/. We anticipate that this timely tool will be of use to cardiac computational and experimental physiologists alike who study cardiac ultrastructure and its role in heart function.
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2,335,003 |
PCORnet Antibiotics and Childhood Growth Study: Process for Cohort Creation and Cohort Description.
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The National Patient-Centered Clinical Research Network (PCORnet) supports observational and clinical research using health care data. The PCORnet Antibiotics and Childhood Growth Study is one of PCORnet's inaugural observational studies. We sought to describe the processes used to integrate and analyze data from children across 35 participating institutions, the cohort characteristics, and prevalence of antibiotic use.</AbstractText>We included children in the cohort if they had at least one same-day height and weight measured in each of 3 age periods: 1) before 12 months, 2) 12 to 30 months, and 3) after 24 months. We distributed statistical queries that each institution ran on its local version of the PCORnet Common Data Model, with aggregate data returned for analysis. We defined overweight or obesity as age- and sex-specific body mass index ≥85th percentile, obesity ≥95th percentile, and severe obesity ≥120% of the 95th percentile.</AbstractText>A total of 681,739 children met the cohort inclusion criteria, and participants were racially/ethnically diverse (24.9% black, 17.5% Hispanic). Before 24 months of age, 55.2% of children received at least one antibiotic prescription; 21.3% received a single antibiotic prescription; 14.3% received 4 or more; and 33.3% received a broad-spectrum antibiotic. Overweight and obesity prevalence was 27.6% at age 4 to <6 years (n = 362,044) and 36.2% at 9 to <11 years (n = 58,344).</AbstractText>The PCORnet Antibiotics and Childhood Growth Study is a large national longitudinal observational study in a diverse population that will examine the relationship between early antibiotic use and subsequent growth patterns in children.</AbstractText>Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,004 |
Physiological and performance changes in national and international judo athletes during block periodization training.
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Block periodization (BP) has been proposed as an alternative approach for application in the context of high-level sports. Despite its growing acceptance, there is no empirical evidence of BP adoption in high-level judo athletes. Therefore, this study aimed to compare the maximal strength, muscle power, judo-specific performances, and hormonal concentration changes of state/national level (NG) and international level (IG) judo athletes subjected to BP. Twenty-one elite judo athletes (international level = 10; 21.7±1.9 years, 167.2±7.6 cm, 67.6±9.4 kg, 15.7±1.9 years of practice; national level = 11; 21.9±3.0 years, 167.5±9.1 cm, 71.8±16.5, 15.9±3.0 years of practice) were subjected to 13-week BP training (5-week accumulation phase [ACP], 5-week transmutation phase [TP], and 3-week realization phase [RP]). The judo-specific performance (SJFT) increased as there was observed a decrease in the SJFT index (final heart rate [HR] (bpm) + HR1 min after the test divided by the number of throws) for both NG (effect size [ES] = 0.83) and IG (ES = 0.53) from ACP to TP (p < 0.05). The row exercise maximal strength decreased (p < 0.05; ES = 1.35) after the ACP but returned to the baseline level after the TP, for the whole group (ES = 1.39). The athletes did seem to cope appropriately with the demands of BP, as besides increases in SJFT performance no significant changes were observed for cortisol and testosterone concentrations. This is the first study to demonstrate that judo athletes from different competitive levels subjected to BP improved SJFT, likely due to an appropriate balance between training loads and recovery. Thus, the BP approach may be a useful alternative periodization strategy for high-level judo athletes.
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2,335,005 |
α-Catenin-dependent cytoskeletal tension controls Yap activity in the heart.
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Shortly after birth, muscle cells of the mammalian heart lose their ability to divide. At the same time, the N-cadherin/catenin cell adhesion complex accumulates at the cell termini, creating a specialized type of cell-cell contact called the intercalated disc (ICD). To investigate the relationship between ICD maturation and proliferation, αE-catenin (<i>Ctnna1</i>) and αT-catenin (<i>Ctnna3</i>) genes were deleted to generate cardiac-specific α-catenin double knockout (DKO) mice. DKO mice exhibited aberrant N-cadherin expression, mislocalized actomyosin activity and increased cardiomyocyte proliferation that was dependent on Yap activity. To assess effects on tension, cardiomyocytes were cultured on deformable polyacrylamide hydrogels of varying stiffness. When grown on a stiff substrate, DKO cardiomyocytes exhibited increased cell spreading, nuclear Yap and proliferation. A low dose of either a myosin or RhoA inhibitor was sufficient to block Yap accumulation in the nucleus. Finally, activation of RhoA was sufficient to increase nuclear Yap in wild-type cardiomyocytes. These data demonstrate that α-catenins regulate ICD maturation and actomyosin contractility, which, in turn, control Yap subcellular localization, thus providing an explanation for the loss of proliferative capacity in the newborn mammalian heart.
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2,335,006 |
Structure of full-length human TRPM4.
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Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na<sup>+</sup>-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
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2,335,007 |
Predicting treatment outcome of drug-susceptible tuberculosis patients using machine-learning models.
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Tuberculosis (TB) is a deadly contagious disease and a serious global health problem. It is curable but due to its lengthy treatment process, a patient is likely to leave the treatment incomplete, leading to a more lethal, drug resistant form of disease. The World Health Organization (WHO) propagates Directly Observed Therapy Short-course (DOTS) as an effective way to stop the spread of TB in communities with a high burden. But DOTS also adds a significant burden on the financial feasibility of the program. We aim to facilitate TB programs by predicting the outcome of the treatment of a particular patient at the start of treatment so that their health workers can be utilized in a targeted and cost-effective way. The problem was modeled as a classification problem, and the outcome of treatment was predicted using state-of-art implementations of 3 machine learning algorithms. 4213 patients were evaluated, out of which 64.37% completed their treatment. Results were evaluated using 4 performance measures; accuracy, precision, sensitivity, and specificity. The models offer an improvement of more than 12% accuracy over the baseline prediction. Empirical results also revealed some insights to improve TB programs. Overall, our proposed methodology will may help teams running TB programs manage their human resources more effectively, thus saving more lives.
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2,335,008 |
Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial.
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Atrial fibrillation is the commonest arrhythmia which raises the risk of heart failure, thromboembolic stroke, morbidity and death. Pharmacological treatments of this condition are focused on heart rate control, rhythm control and reduction in risk of stroke. Selective ablation of cardiac tissues resulting in isolation of areas causing atrial fibrillation is another treatment strategy which can be delivered by two minimally invasive interventions: percutaneous catheter ablation and thoracoscopic surgical ablation. The main purpose of this trial is to compare the effectiveness and safety of these two interventions.</AbstractText><AbstractText Label="METHODS/DESIGN" NlmCategory="METHODS">Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre, randomised controlled trial within three NHS tertiary cardiovascular centres specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with symptomatic, long-standing, persistent atrial fibrillation will be randomly allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio. Pre-determined lesion sets will be delivered in each treatment arm with confirmation of appropriate conduction block. All patients will have an implantable loop recorder (ILR) inserted subcutaneously immediately following ablation to enable continuous heart rhythm monitoring for at least 12 months. The devices will be programmed to detect episodes of atrial fibrillation and atrial tachycardia ≥ 30 s in duration. The patients will be followed for 12 months, completing appropriate clinical assessments and questionnaires every 3 months. The ILR data will be wirelessly transmitted daily and evaluated every month for the duration of the follow-up. The primary endpoint in the study is freedom from atrial fibrillation and atrial tachycardia at the end of the follow-up period.</AbstractText>The CASA-AF Trial is a National Institute for Health Research-funded study that will provide first-class evidence on the comparative efficacy, safety and cost-effectiveness of thoracoscopic surgical ablation and conventional percutaneous catheter ablation for long-standing persistent atrial fibrillation. In addition, the results of the trial will provide information on the effects on patients' quality of life.</AbstractText>ISRCTN Registry, ISRCTN18250790 . Registered on 24 April 2015.</AbstractText>
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2,335,009 |
Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and sedation.
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We evaluated the effects of intravenous dexmedetomidine during spinal anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and compared them with those of saline infusion. Sixty American Society of Anesthesiologists physical status I and II cases were randomly divided into two groups. Patients were connected to the monitor after premedication, and spinal anesthesia was administered. Sensory and motor blockades were assessed using pinprick test and Bromage scale, respectively. Group I received dexmedetomidine infusion and Group II received saline infusion. Throughout the infusion process, hemodynamic data, respiratory rate, oxygen saturation, sedation, pain, Bromage score, amnesia, bispectral index, and side effects were recorded. Postoperative hemodynamic measurements, oxygen saturation, sedation, pain scores were obtained. Sedation and pain were evaluated using the Ramsay and visual analog scales, respectively. Analgesics were administered in cases with high scores on the visual analog scale. Postoperative analgesic consumption, side effects, treatments were recorded. No significant differences were found between the groups with respect to oxygen saturation, respiratory rate, pain, and side effects in the intraoperative period. Time to onset of sensorial block, maximum sensorial block, onset of motor block, and maximum motor block; bispectral index values; and apex heartbeat until 80 min of infusion, systolic arterial blood pressure until 90 min, and diastolic arterial blood pressure until 50 min were lower, whereas amnesia and sedation levels were higher in dexmedetomidine group. Postoperative pain and analgesic requirement were not different. Apex heartbeat at 15 min and systolic arterial blood pressure at 30 min were lower and sedation scores were higher in the dexmedetomidine infusion group. We demonstrated dexmedetomidine infusion had a hemodynamic depressant effect intraoperatively whereas it had no significant effect on peripheral oxygen saturation, respiratory rate, visual analog scale scores, and side effects. Dexmedetomidine infusion enhanced motor and sensory blockade quality and induced amnesia and sedation.
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2,335,010 |
Computerised interpretation of the fetal heart rate during labour: a randomised controlled trial (INFANT).
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Continuous electronic fetal monitoring (EFM) in labour is widely used and computerised interpretation has the potential to increase its utility.</AbstractText>This trial aimed to find out whether or not the addition of decision support software to assist in the interpretation of the cardiotocograph (CTG) reduced the number of poor neonatal outcomes, and whether or not it was cost-effective.</AbstractText>Two-arm individually randomised controlled trial. The allocations were computer generated using stratified block randomisation employing variable block sizes. The trial was not masked.</AbstractText>Labour wards in England, Scotland and the Republic of Ireland.</AbstractText>Women in labour having EFM, with a singleton or twin pregnancy, at ≥ 35 weeks' gestation.</AbstractText>Decision support or no decision support.</AbstractText>The primary outcomes were (1) a composite of poor neonatal outcome {intrapartum stillbirth or early neonatal death (excluding lethal congenital anomalies), or neonatal morbidity [defined as neonatal encephalopathy (NNE)], or admission to a neonatal unit within 48 hours for ≥ 48 hours (with evidence of feeding difficulties, respiratory illness or NNE when there was evidence of compromise at birth)}; and (2) developmental assessment at the age of 2 years in a subset of surviving children.</AbstractText>Between 6 January 2010 and 31 August 2013, 47,062 women were randomised and 46,042 were included in the primary analysis (22,987 in the decision support group and 23,055 in the no decision support group). The short-term primary outcome event rate was higher than anticipated. There was no evidence of a difference in the incidence of poor neonatal outcome between the groups: 0.7% (n</i> = 172) of babies in the decision support group compared with 0.7% (n</i> = 171) of babies in the no decision support group [adjusted risk ratio 1.01, 95% confidence interval (CI) 0.82 to 1.25]. There was no evidence of a difference in the long-term primary outcome of the Parent Report of Children's Abilities-Revised with a mean score of 98.0 points [standard deviation (SD) 33.8 points] in the decision support group and 97.2 points (SD 33.4 points) in the no decision support group (mean difference 0.63 points, 95% CI -0.98 to 2.25 points). No evidence of a difference was found for health resource use and total costs. There was evidence that decision support did change practice (with increased fetal blood sampling and a lower rate of repeated alerts).</AbstractText>Staff in the control group may learn from exposure to the decision support arm of the trial, resulting in improved outcomes in the control arm. This was identified in the planning stage and felt to be unlikely to have a significant effect on the results. As this was a pragmatic trial, the response to CTG alerts was left to the attending clinicians.</AbstractText>This trial does not support the hypothesis that the use of computerised interpretation of the CTG in women who have EFM in labour improves the clinical outcomes for mothers or babies.</AbstractText>There continues to be an urgent need to improve knowledge and training about the appropriate response to CTG abnormalities, including timely intervention.</AbstractText>Current Controlled Trials ISRCTN98680152.</AbstractText>This project was funded by the National Institute for Health Research (NIHR) HTA programme and will be published in full in Health Technology Assessment</i>; Vol. 22, No. 9. See the NIHR Journals Library website for further project information. Sara Kenyon was part funded by the NIHR Collaboration for Leadership in Applied Health Research and Care West Midlands.</AbstractText>
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2,335,011 |
Endogenous Tumor Suppressor microRNA-193b: Therapeutic and Prognostic Value in Acute Myeloid Leukemia.
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Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo. Results miR-193b exerted important, endogenous, tumor-suppressive functions on the hematopoietic system. miR-193b-3p was downregulated in several cytogenetically defined subgroups of pediatric and adult AML, and low expression served as an independent indicator for poor prognosis in pediatric AML (risk ratio ± standard error, -0.56 ± 0.23; P = .016). miR-193b-3p expression improved the prognostic value of the European LeukemiaNet risk-group stratification or a 17-gene leukemic stemness score. In knockout mice, loss of miR-193b cooperated with Hoxa9/Meis1 during leukemogenesis, whereas restoring miR-193b expression impaired leukemic engraftment. Similarly, expression of miR-193b in AML blasts from patients diminished leukemic growth in vitro and in mouse xenografts. Mechanistically, miR-193b induced apoptosis and a G1/S-phase block in various human AML subgroups by targeting multiple factors of the KIT-RAS-RAF-MEK-ERK (MAPK) signaling cascade and the downstream cell cycle regulator CCND1. Conclusion The tumor-suppressive function is independent of patient age or genetics; therefore, restoring miR-193b would assure high antileukemic efficacy by blocking the entire MAPK signaling cascade while preventing the emergence of resistance mechanisms.
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2,335,012 |
A histone deacetylase 3-dependent pathway delimits peripheral myelin growth and functional regeneration.
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Deficits in Schwann cell-mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice. HDAC3 antagonizes the myelinogenic neuregulin-PI3K-AKT signaling axis. Moreover, genome-wide profiling analyses revealed that HDAC3 represses promyelinating programs through epigenetic silencing while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include the HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann cell-specific deletion of either Hdac3 or Tead4 in mice resulted in an elevation of myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3-TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair.
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2,335,013 |
Effective dose of dexmedetomidine as an adjuvant sedative to peripheral nerve blockade in elderly patients.
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The median effective dose (ED50</sub> ) of sedative dexmedetomidine adjuvant to peripheral nerve block (PNB) has not yet been verified in elderly patients. This study assessed the ED50</sub> of intravenous dexmedetomidine for sedation in elderly patients who were undergoing total knee arthroplasty (TKA) with PNB.</AbstractText>Forty-two patients aged 65-85 years were included and stratified into two groups according to age: young-old group (aged 65-74 years) and middle-old group (aged 75-85 years). After the PNB was performed, a pre-calculated dose of dexmedetomidine was administered for 10 min. The Observer's Assessment of Alertness/Sedation scale, bispectral index score, blood pressure and heart rate were recorded. ED50</sub> values of dexmedetomidine for adequate sedation were estimated by the up-and-down method of Dixon and probit regression.</AbstractText>The ED50</sub> of single-dose dexmedetomidine adjuvant to PNB was 0.57 μg/kg (95% confidence interval [CI], 0.47-0.65) in the young-old group and 0.38 μg/kg (95% CI, 0.28-0.46) in the middle-old group. The ED50</sub> of dexmedetomidine differed significantly between the two groups (P < 0.001). In addition, no significant adverse hemodynamic or hypoxemic effects were noted.</AbstractText>We determined the ED50</sub> for sedation using intravenous dexmedetomidine adjuvant to PNB in elderly patients. The ED50</sub> of dexmedetomidine in the middle-old group decreased by 33% compared with that in the young-old group with a mean age difference of 11 years between the two groups.</AbstractText>© 2018 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.</CopyrightInformation>
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2,335,014 |
Prophylactic granisetron for post-spinal anesthesia shivering in cesarean section: A randomized controlled clinical study.
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The serotonergic system is known to be involved in control of post-anesthetic shivering. Our hypothesis was that prophylactic granisetrone (serotonin antagonist) might reduce incidence of post-spinal anesthesia shivering in cesarean section.</AbstractText>Parturient scheduled for elective cesarean delivery under spinal anesthesia were allocated to receive 0.9% saline (Group I, n = 71), 1 mg granisetron (Group II, n = 69), or 0.7 mg granisetron (Group III, n = 72) before the spinal block. Assessment parameters included; hemodynamics, tympanic membrane temperature, neonatal Apgar score, shivering score, patient satisfaction scores about shivering prophylaxis and adverse effects.</AbstractText>Clinically significant shivering was recorded in 55/71 patients (77.5%) in group I, 11/69 (15.9%) in group II and 21/72 (29.2%) in group III (P = 0.000). The intensity of shivering was significantly lower in patients who received granisetron 1 mg compared with granisetron 0.7 mg or saline (P = 0.000). Patients who received prophylactic granisetron 1 mg reported lower mean intraoperative arterial pressure and heart rate values and consumed higher doses of iv ephedrine compared with 0.7 mg granisetron or saline placebo (P < 0.05). Pruritus significantly decreased from (22.5%) in control group to (0%) in granisetron groups (P = 0.000). Nausea was reported in 8 vs 10 and four in group I, II and III, respectively (P < 0.03). Sixteen vs eight and six patients vomited in group I, II, and III, respectively (P < 0.03). Higher patient satisfaction scores were recorded in group II (9.83 ± 0.29, P < 0.03) and III (9.14 ± 1.04, P < 0.04), compared with control group (8.23 ± 1.14).</AbstractText>Prophylactic granisetron effectively reduced incidence and severity of perioperative shivering in a dose dependent manner, compared to placebo controls.</AbstractText>© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.</CopyrightInformation>
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2,335,015 |
Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression.
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Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS.</AbstractText>This prospective study was conducted on 511 mother-infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS.</AbstractText>The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m2</sup>, 11-20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T4</sub>in anaesthesia-related modelling (P</i> < 0.05).</AbstractText>Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS.</AbstractText>
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2,335,016 |
Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.
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<b>Rationale:</b> Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. <b>Objective</b>: To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. <b>Methods and Results</b>: Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I<sub>Ks</sub>), sufficient to abolish I<sub>Ks</sub>-mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake into the sarcoplasmic reticulum is a major mechanism by which SNS suppresses alternans in the guinea pig heart. <b>Conclusions</b>: SNS suppresses calcium and action potential alternans in the intact guinea pig heart by an action mediated through accelerated Ca handling and via increased I<sub>Ks</sub>.
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2,335,017 |
Management of Complications Caused by a Massive Left Ventricle Tumor in a Neonate.
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We report the case of a neonate born with a giant fibroma occupying the entirety of her left ventricle. Owing to the extensive resection, her postoperative course was complicated by severely diminished left ventricular function and complete heart block necessitating extracorporeal support. Ultimately, cardiac resynchronization therapy was used, after which the infant's ventricular function gradually improved and she was successfully discharged to home.
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2,335,018 |
Associations of Long-Term Tea Consumption with Depressive and Anxiety Symptoms in Community-Living Elderly: Findings from the Diet and Healthy Aging Study.
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To examine the association between long-term tea consumption and depressive and anxiety symptoms in community-living elderly.</AbstractText>Community based cross-sectional study.</AbstractText>The Diet and Healthy Aging Study (DaHA), a prospective cohort study in Singapore.</AbstractText>614 elderly aged 60 years and above, who were free of dementia and cognitive impairment.</AbstractText>Information on tea consumption was obtained through interviewer-administered questionnaire. Long-term tea drinking was defined as regular consumption for at least 15 years. Depressive and anxiety symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15) and the 20-item Geriatric Anxiety Inventory (GAI), respectively. A generalized structural equation model (gSEM) was applied to ascertain the association between long-term tea consumption and depressive and anxiety symptoms.</AbstractText>About 59% of the subjects had consumed tea for over 15 years. Long term tea consumption was significantly associated with a reduced odds of having depressive and anxiety symptoms, after adjusting for demographics (i.e., age, gender, education and ethnicity), comorbid conditions (i.e., heart disease, diabetes, stroke, hypertension and hyperlipidaemia) and long-term coffee consumption.</AbstractText>There was evidence suggesting that long-term tea consumption was associated with reduced depressive and anxiety symptoms among community-living elderly. This suggests that it is worthwhile to further investigate the role of tea's bioactive compounds in promoting mental health in aging.</AbstractText>
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2,335,019 |
Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.
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Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl.</AbstractText>Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation).</AbstractText>Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001).</AbstractText>Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD.</AbstractText>© 2018 The Author(s) Published by S. Karger AG, Basel.</CopyrightInformation>
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2,335,020 |
Classic versus Inguinal Approach for Obturator Nerve Block in Transurethral Resection of Bladder Cancer under Spinal Anesthesia: A Randomized Controlled Trial.
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Single spinal anesthesia in transurethral resection of bladder tumor (TURBT) has been reported to be unable to prevent obturator nerve stimulation and adductor muscle contraction, which can cause complications like bladder perforation. The present study aimed to compare the effectiveness of the classic and inguinal approaches for obturator nerve block (ONB ). Seventy patients with cancers of the lateral wall of the bladder, scheduled to undergo TURBT at Imam Reza Hospital (Tabriz, Iran) during a 6-month period as of June 2016, were randomly allocated to groups of inguinal and classic methods (n=35). After the infusion of 500 mL of normal saline, spinal anesthesia was commenced using 3 mL (15 mg) of bupivacaine. Then ONB was performed using 10 mL of 1% lidocaine via the inguinal or classic approach in the inguinal group or the classic group, respectively. The success rate, defined as lack of post-block contraction with stimulation or during surgery, number of puncture attempts, time of block onset, and patient and surgeon satisfaction, was compared between the 2 methods using SPSS, version 19. The success rate of ONB was significantly higher in the inguinal group (97.1% vs. 71.4%; P=0.003). The number of puncture attempts in the classic group was more than that in the inguinal group (3.71±1.10 vs. 1.66±0.68, respectively; P<0.001). The block onset time was shorter in the inguinal group (1.5±0.66 min vs. 2.9±1.18 min; P<0.001). Dissatisfaction of the patient (19 cases vs. 2 cases) and the surgeon (10 cases vs. no case) was higher in the classic group (P<0.001). Compared to the classic approach, the inguinal approach for ONB appeared to be an easily performable, effective block with a high success rate, rapid onset, and good patient and surgeon satisfaction.</AbstractText>IRCT 201608171772N21.</AbstractText>
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2,335,021 |
Ozone therapy induced sinus arrest in a hypertensive patient with chronic kidney disease: A case report.
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Ozone autohemotherapy as an alternative treatment method has been applied to the treatment of several diseases. Here, we report a patient used ozone autohemotherapy to treat her hypertension and diabetes. Nevertheless, the patient occurred sudden dizziness and black haze due to hyperkalemia.</AbstractText>A 54-year-old woman who was admitted to our emergency department complaining of sudden dizziness and black haze for 5 hours.</AbstractText>The blood potassium test showed hyperkalemia. Upon further inquiry of her medical history, the patient received ozone autohemotherapy to treat hypertension and diabetes for 9 days prior to admission.</AbstractText>The ozone therapy had been asked to stop. Insulin, sodium bicarbonate, and sodium polystyrene sulfonate were administered to the patient.</AbstractText>After treatment, blood potassium remained in the normal range. After 3 days of treatment, the 24-hour dynamic electrocardiogram revealed sinus rhythm with an average heart rate of 82 beats/min, occasional ventricular premature beats, occasional ventricular premature beats, and no ST segment depression.</AbstractText>Although ozone therapy is widely used in the treatment of several diseases, adverse reactions should be given attention in clinical practice, especially in patients with chronic kidney disease.</AbstractText>Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.</CopyrightInformation>
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2,335,022 |
Electrospun aniline-tetramer-<i>co</i>-polycaprolactone fibres for conductive, biodegradable scaffolds.
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Conjugated polymers have been proposed as promising materials for scaffolds in tissue engineering applications. The restricted processability and biodegradability of conjugated polymers limit their use for biomedical applications however. Here we synthesised a block-<i>co</i>-polymer of aniline tetramer and PCL (AT-PCL), and processed it into fibrous non-woven scaffolds by electrospinning. We showed that fibronectin (Fn) adhesion was dependant on the AT-PCL oxidative state, with a reduced Fn unfolding length on doped membranes. Furthermore, we demonstrated the cytocompatibility and potential of these membranes to support the growth and osteogenic differentiation of MC3T3-E1 over 21 days.
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2,335,023 |
miRNA-23a/CXCR4 regulates neuropathic pain via directly targeting TXNIP/NLRP3 inflammasome axis.
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Chemokine CXC receptor 4 (CXCR4) in spinal glial cells has been implicated in neuropathic pain. However, the regulatory cascades of CXCR4 in neuropathic pain remain elusive. Here, we investigated the functional regulatory role of miRNAs in the pain process and its interplay with CXCR4 and its downstream signaling.</AbstractText>miRNAs and CXCR4 and its downstream signaling molecules were measured in the spinal cords of mice with sciatic nerve injury via partial sciatic nerve ligation (pSNL). Immunoblotting, immunofluorescence, immunoprecipitation, and mammal two-hybrid and behavioral tests were used to explore the downstream CXCR4-dependent signaling pathway.</AbstractText>CXCR4 expression increased in spinal glial cells of mice with pSNL-induced neuropathic pain. Blocking CXCR4 alleviated the pain behavior; contrarily, overexpressing CXCR4 induced pain hypersensitivity. MicroRNA-23a-3p (miR-23a) directly bounds to 3' UTR of CXCR4 mRNA. pSNL-induced neuropathic pain significantly reduced mRNA expression of miR-23a. Overexpression of miR-23a by intrathecal injection of miR-23a mimics or lentivirus reduced spinal CXCR4 and prevented pSNL-induced neuropathic pain. In contrast, knockdown of miR-23a by intrathecal injection of miR-23a inhibitor or lentivirus induced pain-like behavior, which was reduced by CXCR4 inhibition. Additionally, miR-23a knockdown or CXCR4 overexpression in naïve mice could increase the thioredoxin-interacting protein (TXNIP), which was associated with induction of NOD-like receptor protein 3 (NLRP3) inflammasome. Indeed, CXCR4 and TXNIP were co-expressed. The mammal two-hybrid assay revealed the direct interaction between CXCR4 and TXNIP, which was increased in the spinal cord of pSNL mice. In particular, inhibition of TXNIP reversed pain behavior elicited by pSNL, miR-23a knockdown, or CXCR4 overexpression. Moreover, miR-23a overexpression or CXCR4 knockdown inhibited the increase of TXNIP and NLRP3 inflammasome in pSNL mice.</AbstractText>miR-23a, by directly targeting CXCR4, regulates neuropathic pain via TXNIP/NLRP3 inflammasome axis in spinal glial cells. Epigenetic interventions against miR-23a, CXCR4, or TXNIP may potentially serve as novel therapeutic avenues in treating peripheral nerve injury-induced nociceptive hypersensitivity.</AbstractText>
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2,335,024 |
Apparent pacemaker dysfunction during peptide receptor radionuclide therapy for neuroendocrine tumor.
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This case is a reminder not to overlook rare causes of electrolyte shifts, which may cause reversible changes in pacemaker pacing thresholds.
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2,335,025 |
The usefulness of interpectoral block as an analgesic technique in breast cancer surgery.
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To compare the analgesic efficacy of continuous interpectoral block (CIPB) compared to intravenous analgesia (IV) after breast surgery.</AbstractText>A prospective, comparative and randomised study of women aged from 18-75years, ASAI-III, operated for breast cancer. In group1 (CIPB) after general anaesthetic, an ultrasound-guided interpectoral catheter was placed and 30mL of 0.5% ropivacaine was administered through it. In the event of an increase in heart rate and blood pressure >15% after the surgical incision, intravenous fentanyl 1μg·kg-1</sup> was administered, repeating the dose as necessary. In the postoperative period, perfusion of ropivacaine 0.2% 5mL·h-1</sup>; with PCA bolus 5mL/30minutes was administered through the catheter for 24hours and rescue analgesia prescribed with 5mg subcutaneous morphine chloride. In group2 (IV), after induction of general anaesthesia, intravenous fentanyl was administered in the same way as in the other group. The patients received metamizole 2g with dexketoprofen 50mg and ondansetron 4mg postoperatively followed by perfusion of metamizole 4%, tramadol 0.2% and ondansetron 0.08% 2ml·h-1</sup>; with PCA bolus 2mL/20min for 24hours. The same rescue analgesia was prescribed. The principal variables recorded were pain at rest and during movement, according to a simple verbal scale (VAS 0-10) and the rescue analgesia required on discharge from recovery, at 12 and at 24hours.</AbstractText>137 patients were included: 81 in group1 (59.12%) and 56 in group2 (40.87%). No significant differences were observed in the analgesia between either group, but differences were observed in the dose of intraoperative fentanyl (P<.05). Differences that were not significant were observed in the rescue analgesia required on recovery (10% fewer on group1).</AbstractText>Both techniques provided effective postoperative analgesia, but the CIPB group required significantly less intraoperative fentanyl.</AbstractText>Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.</CopyrightInformation>
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2,335,026 |
Facilitation of Vaginal Delivery in an Infant with Complete Heart Block Secondary to Maternal Anti-Ro Antibodies.
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Congenital heart block (CHB) is a rare disorder that may be associated with a high morbidity and even mortality, with a risk of death both in utero and during infancy. Women with serum titres of anti-Ro and/or anti-La antibodies carry a risk of CHB of 1-5% in their offspring, with a recurrence risk of approximately 20%. We present a case of a 36-year-old female with a pregnancy complicated by congenital heart block. Autoimmune profiling at booking showed she was positive for lupus anticoagulant and anti-Ro antibodies. A fetal echocardiogram at 21 + 3 showed complete heart block. She was monitored throughout the remainder of her pregnancy with serial growth scans, cardiovascular profiling, and BPP scoring. She had a normal vaginal delivery at term to a female infant.
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2,335,027 |
Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion.
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Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6) hearts underwent 25-min global ischemia (37°C) and 30-min reperfusion. In treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly and reversibly block the ETC at complex I. Mitochondria were isolated at the end of reperfusion and subjected to unbiased proteomic analysis using tryptic digestion followed by liquid chromatography-mass spectrometry with isotope tags for relative and absolute quantification. Amobarbital treatment decreased cardiac injury and protected respiration. I/R decreased the content ( P < 0.05) of multiple mitochondrial matrix enzymes involved in intermediary metabolism compared with the time control. The contents of several enzymes in fatty acid oxidation were decreased compared with the time control. Blockade of ETC during ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but also multiple pathways of intermediary metabolism sustain damage initiated by the ETC. If these damaged mitochondria persist in the myocyte, they remain a potent stimulus for ongoing injury and the transition to cardiomyopathy during prolonged reperfusion. Modulation of ETC function during early reperfusion is a key strategy to preserve mitochondrial metabolism and to decrease persistent mitochondria-driven injury during longer periods of reperfusion that predispose to ventricular dysfunction and heart failure. NEW & NOTEWORTHY Ischemia-reperfusion (I/R) damages mitochondria, which could be protected by reversible blockade of the electron transport chain (ETC). Unbiased proteomics with isotope tags for relative and absolute quantification analyzed mitochondrial damage during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty acid oxidation, and ETC decreased, which could be prevented by ETC blockade. Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.
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2,335,028 |
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
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The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs) in myeloid culture and induce lymphoid leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is strongly associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 contributes significantly to the block in differentiation, which is the pathognomonic feature of human acute leukemias.
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2,335,029 |
Single-dose intravenous iron in Southeast Asian heart failure patients: A pilot randomized placebo-controlled study (PRACTICE-ASIA-HF).
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Iron deficiency is highly prevalent in Southeast Asians with heart failure (HF) and associated with worse outcomes. This trial aimed to assess the effect of intravenous iron in Southeast Asians hospitalized with decompensated HF.</AbstractText>Fifty patients hospitalized for acute decompensated HF, regardless of ejection fraction, with iron deficiency (defined as serum ferritin <300 ng/mL if transferrin saturation is <20%) were randomized to receive either one dose of intravenous ferric carboxymaltose (FCM) 1000 mg or placebo (0.9% saline) following HF stabilization and before discharge in two Singapore tertiary centres. The primary endpoint was difference in 6-min walk test (6MWT) distance over 12 weeks, while secondary endpoints were quality of life assessed using validated Kansas City Cardiomyopathy Questionnaire (KCCQ) and Visual Analogue Scale (VAS). Improvement in 6MWT distance at Week 12 was observed in both FCM and placebo groups (from 252 ± 123 to 334 ± 128 m and from 243 ± 67 to 301 ± 83 m, respectively). Unadjusted analysis showed 6MWT distance for FCM exceeded that for placebo, but adjustment for baseline covariates and time attenuated this effect {adjusted mean difference between groups: 0.88 m [95% confidence interval (CI) -30.2 to 32.0, P = 0.956]}. KCCQ overall summary and VAS were similar in both groups [adjusted mean difference: KCCQ -1.48 (95% CI -8.27 to 5.31, P = 0.670) and VAS 0.26 (95% CI -0.33 to 0.86, P = 0.386)]. FCM was well tolerated with no serious treatment-related adverse events.</AbstractText>Intravenous FCM administered pre-discharge in Southeast Asians hospitalized with decompensated HF is clinically feasible. Changes in 6MWT distance should be measured beyond Week 12 to account for background therapy effects.</AbstractText>© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.</CopyrightInformation>
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2,335,030 |
Relationships between road-distance to primary care facilities and ischemic heart disease and stroke mortality in Hokkaido, Japan: A Bayesian hierarchical approach to ecological count data.
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Poor access to a primary care physician may lead to poor control of risk factors for disease. This study investigated whether geographic access to a primary care physician was related to ischemic heart disease and stroke mortality.</AbstractText>Road-distances from the centroids of the basic unit blocks of the 2010 Japanese Census to the nearest primary care facilities in Hokkaido, northern Japan, were measured using geographic information system (GIS) software. Next, block population-weighted mean road-distances to primary care facilities in all municipalities were calculated. The numbers of deaths from ischemic heart disease and stroke were obtained from the Vital Statistics Bureau. A Bayesian spatial conditional autoregressive (CAR) model was used to analyze relative risk (RR) by road-distance with the numbers of physicians in the municipality included as a covariate.</AbstractText>Relative risk (per 1 kilometer increased) of death from ischemic heart disease to road-distance to the nearest primary care facility was not significantly higher in men (1.108: 95% credible interval [CI] 0.999-1.037) and women (1.023: 95% CI 1.000-1.046). However, RR of death from stroke was significantly higher in men (1.019: 95% CI 1.005-1.032) and women (1.019: 95% CI 1.006-1.033).</AbstractText>Longer road-distance to a primary care facility may increase the risk of stroke mortality.</AbstractText>
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2,335,031 |
Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy.
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Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies. Neuropathies are associated to aberrant excitability of DRG neurons due to the alteration in the expression or function of a variety of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are overexpressed in inflammatory and neuropathic pain states, and HCN blockers have been shown to reduce neuronal excitability and to ameliorate painful states in animal models. However, HCN channels are critical in cardiac action potential, and HCN blockers used so far in pre-clinical models do not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we show an HCN current gain of function in DRG neurons from oxaliplatin-treated rats. Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion, this study strengthens the evidence for a disease-specific role of HCN1 in CIPN, and proposes HCN1-selective inhibitors as new-generation pain medications with the desired efficacy and safety profile.
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2,335,032 |
Hepatic Gi signaling regulates whole-body glucose homeostasis.
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An increase in hepatic glucose production (HGP) is a key feature of type 2 diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors critically contributes to pathologically elevated HGP. Here, we tested the hypothesis that this metabolic impairment can be counteracted by enhancing hepatic Gi signaling. Specifically, we used a chemogenetic approach to selectively activate Gi-type G proteins in mouse hepatocytes in vivo. Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase in HGP and severely impaired glucose homeostasis. Moreover, increased Gi signaling stimulated glucose release in human hepatocytes. A lack of functional Gi-type G proteins in hepatocytes reduced blood glucose levels and protected mice against the metabolic deficits caused by the consumption of a high-fat diet. Additionally, we delineated a signaling cascade that links hepatic Gi signaling to ROS production, JNK activation, and a subsequent increase in HGP. Taken together, our data support the concept that drugs able to block hepatic Gi-coupled GPCRs may prove beneficial as antidiabetic drugs.
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2,335,033 |
Hemodynamic effects of lateral tilt before and after spinal anesthesia during cesarean delivery: an observational study.
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Post-spinal hypotension is a common maternal complication during cesarean delivery. Aortocaval compression by the gravid uterus has been assumed as a precipitating factor for post-spinal hypotension. The role of left lateral tilting position in improving maternal cardiac output after subarachnoid block (SAB) is unclear. The aim of this work is to investigate the effect of left lateral tilting on maternal hemodynamics after SAB.</AbstractText>A prospective observational study was conducted including 105 full term pregnant women scheduled for cesarean delivery. Mean arterial pressure, heart rate, cardiac output (measured by electrical cardiometry), stroke volume, and systemic vascular resistance were recorded in three positions (supine, 150</sup>, and 300</sup> left lateral positions) before SAB, after SAB, and after delivery of the fetus.</AbstractText>Before SAB, no significant hemodynamic changes were reported with left lateral tilting. A significant decrease was reported in mean arterial pressure, cardiac output, stroke volume, and systemic vascular resistance after SAB (in supine position). When performing left lateral tilting, there was an increase in cardiac output, heart rate, and mean arterial pressure. No difference was reported between the two tilt angles (150</sup> and 300</sup>).</AbstractText>Changing position of full term pregnant woman after SAB from supine to left lateral tilted position results increased cardiac output and mean arterial pressure. There is no difference between the two tilt angles (150</sup> and 300</sup>).</AbstractText>clinicaltrials.gov ( NCT02828176 ) retrospectively registered.</AbstractText>
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2,335,034 |
Ether-à-go-go K<sup>+</sup> channels: effective modulators of neuronal excitability.
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Mammalian ether-à-go-go (EAG) channels are voltage-gated K<sup>+</sup> channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart, where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation. They can even support high frequency firing by preventing a depolarization-induced Na<sup>+</sup> channel block. EAG channels are modulated differentially, e.g. eag channels by intracellular Ca<sup>2+</sup> , erg channels by extracellular K<sup>+</sup> and GPCRs, and elk channels by changes in pH. So far, only currents mediated by erg channels have been recorded in neurons with the help of selective blockers. Neuronal eag and elk currents have not been isolated due to the lack of suitable channel blockers. However, findings in KO mice indicate a physiological role of eag1 currents in synaptic transmission and an involvement of elk2 currents in cognitive performance. Human eag1 and eag2 gain-of-function mutations underlie syndromes associated with epileptic seizures.
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2,335,035 |
Relationship of sleep pattern and snoring with chronic disease: findings from a nationwide population-based survey.
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To investigate the association of total sleep time and presence or absence of snoring with chronic disease among the Bangladeshi adult population.</AbstractText>Cross-sectional survey.</AbstractText>Urban and rural Bangladesh.</AbstractText>A total of 12,338 men and women aged ≥35 years.</AbstractText>Total sleep time was considered as the total hours of sleep in 24 hours. Furthermore, sleep time was categorized into <7, 7-9, and >9 hours according to National Sleep Foundation (2015) guidelines. Self-reported snoring history was captured and corroborated with their respective sleep partner/spouse in more than 80% cases. Registered physician-diagnosed current and/or previous cases of hypertension, diabetes, coronary heart disease, cancer, stroke, chronic obstructive pulmonary disease, and any other chronic conditions were counted.</AbstractText>Overall prevalence of at least 1 chronic disease in our study population was around 18%: men (15.4%) and women (20.0%). Hypertension has the highest prevalence (overall: 12.7%, men: 12.2%, women: 15%) followed by diabetes (4.9%), coronary heart diseases (3.2%), stroke (1.8%), chronic obstructive pulmonary disease (0.9%), and cancer (any type: 0.1%). Sleep pattern and snoring are significantly associated with all individual chronic disease except cancer. Sociodemographic, behavioral, and lifestyle variables were adjusted, and inadequate total sleep time (<7 hours) and snoring (yes/no) showed significant association with chronic disease status (risk ratio = 1.11, 95% confidence interval 1.00-1.22 and risk ratio = 1.20, 95% confidence interval 1.11-1.29, respectively).</AbstractText>Inadequate sleep and snoring are independently associated with chronic disease in Bangladeshi adult population and perhaps elsewhere.</AbstractText>Copyright © 2017 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,036 |
Changes in tissue and cerebral oxygenation following spinal anesthesia in infants: a prospective study.
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Use of spinal anesthesia (SA) in children may address concerns about potential neurocognitive effects of general anesthesia. We used near-infrared spectroscopy (NIRS) to assess the effects of SA on cerebral and tissue oxygenation in 19 patients aged 7 ± 3 months. Prior to SA placement, NIRS monitors were placed on the forehead (cerebral) and the thigh (tissue). Intraoperative cerebral and tissue saturation were 73 ± 7 and 80 ± 11%, respectively, before SA placement. NIRS measurements were monitored every minute for 30 min after SA placement and modeled using mixed-effects linear regression. Regression estimates showed that cerebral saturation remained stable from 67% [95% confidence interval (CI) 63, 71%] after SA placement to 68% (95% CI 65, 72%) at the conclusion of monitoring. After SA placement, tissue saturation was elevated compared to baseline values; but further change [from 91% (95% CI 89, 93%) to 93% (95% CI 91, 95%) at the end of monitoring] was clinically non-significant. All patients breathed spontaneously on room air without changes in oxygen saturation. Blood pressure and heart rate decreased after SA placement, but no changes in hemodynamic parameters required treatment. These data provide further evidence of the neutral effect of SA on cerebral oxygenation 30 min after block placement.
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2,335,037 |
P-wave and interatrial block: New predictor for atrial high rate episodes in patients with cardiac implantable electronic devices.
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The presence of interatrial block (IAB) is associated with the development of atrial fibrillation (AF). The aim of this study was to determine whether P-wave duration and presence of IAB before the implantation of a cardiac implantable electronic device (CIED) are associated with the presence of atrial high rate episodes (AHRE), during long-term follow-up.</AbstractText>380 patients (57% men; 75 ± 10 years) were included. IAB was defined according to the International Consensus Criteria. AHRE was defined as an episode of atrial rate ≥225 beats/min with a minimum duration of 5 minutes.</AbstractText>Documented paroxysmal AF before the implantation was present in 24% of the patients; 80% had hypertension and 32% structural heart disease. Mean P-wave duration was 123 ± 23 ms, and 39% of the patients had IAB (32% partial, 7% advanced). After a mean follow-up of 18 ± 12 months, 33% of the patients presented AHRE. Patients with AHRE had a P-wave duration significantly longer (130 ± 24 ms vs 119 ± 21 ms; P < 0.001) and a greater prevalence of IAB (53% vs 32%; P < 0.001). In a multivariate analysis, predictors of AHRE were: IAB (odds ratio [OR] 2.1; 95% confidence interval [CI] [1.3-3.4], P < 0.001) and previous paroxysmal AF (OR 2.6; 95% CI [1.5-4.3], P < 0.001). In patients without previous AF, the presence of IAB was also a significant predictor of AHRE (OR 3.1; 95% CI [1.8-5.5], P < 0.001).</AbstractText>IAB is a strong predictor of AHRE in patients with CIED. This finding is independent of the presence of prior paroxysmal AF.</AbstractText>© 2018 Wiley Periodicals, Inc.</CopyrightInformation>
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2,335,038 |
Risk Factors for Clinician-Diagnosed Lyme Arthritis, Facial Palsy, Carditis, and Meningitis in Patients From High-Incidence States.
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Clinical features of Lyme disease (LD) range from localized skin lesions to serious disseminated disease. Information on risk factors for Lyme arthritis, facial palsy, carditis, and meningitis is limited but could facilitate disease recognition and elucidate pathophysiology.</AbstractText>Patients from high-incidence states treated for LD during 2005-2014 were identified in a nationwide insurance claims database using the International Classification of Diseases, Ninth Revision</i> code for LD (088.81), antibiotic treatment history, and clinically compatible codiagnosis codes for LD manifestations.</AbstractText>Among 88022 unique patients diagnosed with LD, 5122 (5.8%) patients with 5333 codiagnoses were identified: 2440 (2.8%) arthritis, 1853 (2.1%) facial palsy, 534 (0.6%) carditis, and 506 (0.6%) meningitis. Patients with disseminated LD had lower median age (35 vs 42 years) and higher male proportion (61% vs 50%) than nondisseminated LD. Greatest differential risks included arthritis in males aged 10-14 years (odds ratio [OR], 3.5; 95% confidence interval [CI], 3.0-4.2), facial palsy (OR, 2.1; 95% CI, 1.6-2.7) and carditis (OR, 2.4; 95% CI, 1.6-3.6) in males aged 20-24 years, and meningitis in females aged 10-14 years (OR, 3.4; 95% CI, 2.1-5.5) compared to the 55-59 year referent age group. Males aged 15-29 years had the highest risk for complete heart block, a potentially fatal condition.</AbstractText>The risk and manifestations of disseminated LD vary by age and sex. Provider education regarding at-risk populations and additional investigations into pathophysiology could enhance early case recognition and improve patient management.</AbstractText>
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2,335,039 |
Novel Reversible Model of Atherosclerosis and Regression Using Oligonucleotide Regulation of the LDL Receptor.
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Animal models have been used to explore factors that regulate atherosclerosis. More recently, they have been used to study the factors that promote loss of macrophages and reduction in lesion size after lowering of plasma cholesterol levels. However, current animal models of atherosclerosis regression require challenging surgeries, time-consuming breeding strategies, and methods that block liver lipoprotein secretion.</AbstractText>We sought to develop a more direct or time-effective method to create and then reverse hypercholesterolemia and atherosclerosis via transient knockdown of the hepatic LDLR (low-density lipoprotein receptor) followed by its rapid restoration.</AbstractText>We used antisense oligonucleotides directed to LDLR mRNA to create hypercholesterolemia in wild-type C57BL/6 mice fed an atherogenic diet. This led to the development of lesions in the aortic root, aortic arch, and brachiocephalic artery. Use of a sense oligonucleotide replicating the targeted sequence region of the LDLR mRNA rapidly reduced circulating cholesterol levels because of recovery of hepatic LDLR expression. This led to a decrease in macrophages within the aortic root plaques and brachiocephalic artery, that is, regression of inflammatory cell content, after a period of 2 to 3 weeks.</AbstractText>We have developed an inducible and reversible hepatic LDLR knockdown mouse model of atherosclerosis regression. Although cholesterol reduction decreased early en face lesions in the aortic arches, macrophage area was reduced in both early and late lesions within the aortic sinus after reversal of hypercholesterolemia. Our model circumvents many of the challenges associated with current mouse models of regression. The use of this technology will potentially expedite studies of atherosclerosis and regression without use of mice with genetic defects in lipid metabolism.</AbstractText>© 2018 American Heart Association, Inc.</CopyrightInformation>
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2,335,040 |
Promoting sustainability in quality improvement: an evaluation of a web-based continuing education program in blood pressure measurement.
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The accuracy of blood pressure measurement is variable in office-based settings. Even when staff training programs are effective, knowledge and skills decay over time, supporting the need for ongoing staff training. We evaluated whether a web-based continuing education program in blood pressure measurement reinforced knowledge and skills among clinical staff and promoted sustainability of an existing quality improvement program.</AbstractText>Medical assistants and nurses at six primary care clinics within a health system enrolled in a 30-min online educational program designed to refresh their knowledge of blood pressure measurement. A 20-question pre- and post-intervention survey addressed learners' knowledge and attitudes. Direct observation of blood pressure measurement technique before and after the intervention was performed. Differences in responses to pre- and post-module knowledge and attitudes questions and in observation data were analyzed using chi-square tests and simple logistic regression.</AbstractText>All 88 clinical staff members participated in the program and completed the evaluation survey. Participants answered 80.6% of questions correctly before the module and 93.4% afterwards (p < 0.01). Scores improved significantly among staff from all job types. Licensed practical nurses and staff who had been in their current job at least a year were more likely to answer questions correctly than registered nurses and those in their current job less than a year. Attitudes toward correct blood pressure measurement were high at baseline and did not improve significantly. Prior to the intervention, staff adhered to 9 of 18 elements of the recommended technique during at least 90% of observations. Following the program, staff was more likely to explain the protocol, provide a rest period, measure an average blood pressure, and record the average blood pressure, but less likely to measure blood pressure with the arm at heart level and use the right arm.</AbstractText>We designed, implemented, and evaluated a web-based educational program to improve knowledge, skills, and attitudes in blood pressure measurement and use of an automated device among nurses and medical assistants in ambulatory care. The program reinforced knowledge related to recommended blood pressure measurement technique.</AbstractText>Retrospectively registered with ClincalTrials.gov on March 22, 2012; registration number NCT01566864 .</AbstractText>
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2,335,041 |
[Reversal of neuromuscular block with sugammadex in five heart transplant pediatric recipients].
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Heart transplantation is a frequent procedure in the treatment of end-stage cardiac dysfunction. Therefore, these patient populations will also be more frequent exposed to other more common surgical procedures after their transplantation. Anesthesiologist should be aware in their assessment of these patients, especially regarding some specific issues related to patients with a history of heart transplantation, like reversal of neuromuscular block. Several reports described that cholinesterase inhibitors drugs, like neostigmine, may produce a dose-dependent life-threatening bradycardia in heart transplant recipients while other publication described the safe use of neostigmine. Reversal of neuromuscular block with sugammadex is another possibility, but limited data exists in literature. We describe five cases in which successful reversal of neuromuscular block was performed with sugammadex in heart transplant pediatric recipients without sequale and discuss the reversal of neuromuscular block in this patient population.<CopyrightInformation>Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Carlos</LastName><ForeName>Ricardo Vieira</ForeName><Initials>RV</Initials><AffiliationInfo><Affiliation>Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Torres</LastName><ForeName>Marcelo Luis Abramides</ForeName><Initials>MLA</Initials><AffiliationInfo><Affiliation>Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Boer</LastName><ForeName>Hans Donald</ForeName><Initials>HD</Initials><AffiliationInfo><Affiliation>Martini General Hospital Groningen, Department of Anesthesiology and Pain Medicine, Groningen, Holanda. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author></AuthorList><Language>por</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Reversão do bloqueio neuromuscular com sugamadex em cinco receptores pediátricos de transplante cardíaco.</VernacularTitle><ArticleDate DateType="Electronic"><Year>2018</Year><Month>01</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>Brazil</Country><MedlineTA>Braz J Anesthesiol</MedlineTA><NlmUniqueID>101624623</NlmUniqueID><ISSNLinking>0104-0014</ISSNLinking></MedlineJournalInfo><OtherAbstract Type="Publisher" Language="eng">Heart transplantation is a frequent procedure in the treatment of end-stage cardiac dysfunction. Therefore, these patient populations will also be more frequent exposed to other more common surgical procedures after their transplantation. Anesthesiologist should be aware in their assessment of these patients, especially regarding some specific issues related to patients with a history of heart transplantation, like reversal of neuromuscular block. Several reports described that cholinesterase inhibitors drugs, like neostigmine, may produce a dose-dependent life-threatening bradycardia in heart transplant recipients while other publication described the safe use of neostigmine. Reversal of neuromuscular block with sugammadex is another possibility, but limited data exists in literature. We describe five cases in which successful reversal of neuromuscular block was performed with sugammadex in heart transplant pediatric recipients without sequelae and discuss the reversal of neuromuscular block in this patient population.
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2,335,042 |
Perfusion index as a predictor of hypotension following propofol induction - A prospective observational study.
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Hypotension during propofol induction is a common problem. Perfusion index (PI), an indicator of systemic vascular resistance, is said to be predictive of hypotension following subarachnoid block. We hypothesised that PI can predict hypotension following propofol induction and a cut-off value beyond which hypotension is more common can be determined.</AbstractText>Fifty adults belonging to the American Society of Anesthesiologists' physical status I/II undergoing elective surgery under general anaesthesia were enrolled for this prospective, observational study. PI, heart rate, blood pressure (BP) and oxygen saturation were recorded every minute from baseline to 10 min following induction of anaesthesia with a titrated dose of propofol, and after endotracheal intubation. Hypotension was defined as fall in systolic BP (SBP) by >30% of baseline or mean arterial pressure (MAP) to <60 mm Hg. Severe hypotension (MAP of <55 mm Hg) was treated.</AbstractText>Within first 5-min after induction, the incidence of hypotension with SBP and MAP criteria was 30% and 42%, respectively, and that of severe hypotension, 22%. Baseline PI <1.05 predicted incidence of hypotension at 5 min with sensitivity 93%, specificity 71%, positive predictive value (PPV) 68% and negative predictive value (NPV) 98%. The area under the ROC curve (AUC) was 0.816, 95% confidence interval (0.699-0.933), P</i> < 0.001.</AbstractText>Perfusion index could predict hypotension following propofol induction, especially before endotracheal intubation, and had a very high negative predictive value.</AbstractText>
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2,335,043 |
Detection of autoantibodies to the p200-epitope of SSA/Ro52 antigen. A comparison of two laboratory assays.
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Anti-p200 antibodies have been receiving growing interest in view of findings associating their presence to risk of fetal autoimmune congenital heart block (CHB). The study compares and evaluates the performance of two assays currently being used for their detection.</AbstractText>One hundred and sixteen pregnant women positive for anti-SSA/Ro52 antibodies were considered as the study population. Fifty women negative for anti-SSA/Ro52 antibodies were considered as the control population. Anti-p200 antibodies were analyzed using two home-made ELISA assays: one with biotinylated antigen and the other with free antigen.</AbstractText>The specificity of the p200-free assay was significantly higher with respect to that of the p200-biotin assay (p=0.023). Both methods showed a high area under curve (AUC), thus, a good accuracy. There was a significant prevalence of anti-p200 antibodies when the p200-free assay was used to analyze the sera of the pregnant women with CHB fetuses (p=0.007). Cohen's κ and Spearman's ρ coefficients showed a good concordance (0.71) and a high correlation (0.93), respectively.</AbstractText>The p200-free assay with respect to the biotin-based method was more specific in detecting p200 antibodies in women positive for anti-SSA/Ro52 antibodies. In addition, only the p200-free method significantly found p200 antibodies in patients with fetal CHB.</AbstractText>
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2,335,044 |
A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma.
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In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% <i>versus</i> 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.
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2,335,045 |
Fibrin and D-dimer bind to monomeric GPVI.
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Fibrin has recently been shown to activate platelets through the immunoglobulin receptor glycoprotein VI (GPVI). In the present study, we show that spreading of human platelets on fibrin is abolished in patients deficient in GPVI, confirming that fibrin activates human platelets through the immunoglobulin receptor. Using a series of proteolytic fragments, we show that D-dimer, but not the E fragment of fibrin, binds to GPVI and that immobilized D-dimer induces platelet spreading through activation of Src and Syk tyrosine kinases. In contrast, when platelets are activated in suspension, soluble D-dimer inhibits platelet aggregation induced by fibrin and collagen, but not by a collagen-related peptide composed of a repeat GPO sequence or by thrombin. Using surface plasmon resonance, we demonstrate that fibrin binds selectively to monomeric GPVI with a K<sub>D</sub> of 302 nM, in contrast to collagen, which binds primarily to dimeric GPVI. These results establish GPVI as the major signaling receptor for fibrin in human platelets and provide evidence that fibrin binds to a distinct configuration of GPVI. This indicates that it may be possible to develop agents that selectively block the interaction of fibrin but not collagen with the immunoglobulin receptor. Such agents are required to establish whether selective targeting of either interaction has the potential to lead to development of an antithrombotic agent with a reduced effect on bleeding relative to current antiplatelet drugs.
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2,335,046 |
Profound Prolonged Bradycardia and Hypotension after Interscalene Brachial Plexus Block with Bupivacaine.
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Interscalene brachial plexus blocks have been a routinely performed method of anesthesia for shoulder surgery that decreases the need for general anesthesia, length of stay, and recovery time. We describe a case of bupivacaine toxicity after an interscalene block.</AbstractText>The patient was a 66-year-old man who presented to our Emergency Department by emergency medical services from an ambulatory surgery center where he had undergone rotator cuff surgery, with bradycardia and hypotension. His symptoms began upon completion of the surgery in which he received interscalene nerve block with bupivacaine and lidocaine. He was given three doses of 0.5 mg atropine and one dose of 1 mg epinephrine for a heart rate of 40 beats/min without any improvement prior to arrival. His bradycardia was refractory to atropine. He was started on a dopamine drip and transferred to the coronary care unit. The timing of his symptoms, minutes after his regional nerve block, and his complete recovery with only supportive care, make the diagnosis of bupivacaine toxicity likely. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the safety profile of local anesthetics, we must be aware of their potential side affects. Whereas most adverse reactions are secondary to misdirection of anesthetic or accidental vascular puncture, local anesthetic systemic toxicity (LAST) is the major cause of significant adverse events with regional anesthesia. As regional anesthesia becomes more common, emergency physicians must be more aware of the potential complications and be able to both diagnose and treat.</AbstractText>Copyright © 2017 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,047 |
Case Study: Cardiac sarcoidosis resolved with Mycobacterium avium paratuberculosis antibiotics (MAP).
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<i>Background:</i> The author presents a clinical history and personal case study following his diagnosis of inactive sarcoidosis in 2004, followed by an acute episode of cardiac sarcoidosis (CS) in 2012 which resulted in complete heart block, cardiac myopathy, heart failure and insertion of an implantable cardioverter defibrillator (ICD) pacemaker. <i>Methods:</i> Following a detailed review of the clinical and scientific literature he concluded that sarcoidosis may be a mycobacterial infection and could be treated with anti-MAP antibiotic regime (1) developed to treat Crohn's disease. <i>Findings:</i> After successful culture and identification of viable MAP in his blood, treatment with the MAP antibiotic regime for one year led to complete metabolic resolution of the previously avid cardiac sarcoidosis and no PET evidence of any metabolically active sarcoidosis anywhere. Such reversal of cardiac sarcoidosis has never previously been reported. <i>(Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 171-177)</i>.
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2,335,048 |
Hidden Figures: Occult Intra-Cardiac Metastases in Asymptomatic Neuroendocrine Tumor Patients.
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Carcinoid heart disease is a devastating paraneoplastic consequence of unchecked hormone production from neuroendocrine tumors (NET) and often results in right-sided heart failure. While it occurs frequently in NET patients with carcinoid syndrome, cardiac metastases occur much less often and are usually only incidentally found. Gallium-68 dotatate (ga-68) is an imaging tracer which binds to somatostatin receptor 2 with greater avidity than Indium-111, the tracer used commonly in octreotide scans. Ga-68 PET/CT is the most sensitive study for detecting occult NET metastases and has emerged as the current imaging gold standard. We describe two cases from Vanderbilt University Medical Center and Stanford University Medical Center where asymptomatic patients with well-differentiated midgut NET were diagnosed with intra-cardiac metastases using ga-68 PET/CT. Management of these patients was altered based on the findings as they underwent extensive cardiac evaluation and initiation of therapy with octreotide. Fortunately, they have not suffered life-threatening cardiac complications seen in some NET patients, from other published series, such as bradycardia, heart block, syncope and arrhythmias. These possibilities suggest early cardiology evaluation and consideration of other therapies beyond octreotide, such as surgery or PRRT, may be essential for all NET patients found to have intra-cardiac metastases.
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2,335,049 |
Anticancer activity of Schiff base-Poloxamer P85 combination against kidney cancer.
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Renal cell carcinoma (RCC) accounts for approximately 80% of the primary renal cancers, and current treatment strategies are not sufficient to provide a certain solution. Since there are not many treatment options, interest in discovery of alternative drugs has increased.</AbstractText>In the current study, anticancer activity of a novel heterodinuclear Cu(II)-Mn(II) complex (Schiff base-SB) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (pluronic) P85 was tested against RCC. Cell viability, apoptosis and gene expression analysis were conducted in vitro by using Renca cells.</AbstractText>The results revealed that the SB-P85 combination decreased cell proliferation by increasing the apoptotic gene expressions and apoptosis. Renca-injected BALB/c mice were used to mimic early stage of RCC model. Treatment with SB-P85 combination suppressed tumor formation and growth compared to baseline.</AbstractText>Overall, SB-P85 showed promising anticancer activity against RCC in vitro and in vivo.</AbstractText>
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2,335,050 |
The effects of interrupting prolonged sitting with intermittent activity on appetite sensations and subsequent food intake in preadolescent children.<Pagination><StartPage>e0188986</StartPage><MedlinePgn>e0188986</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">e0188986</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0188986</ELocationID><Abstract><AbstractText Label="BACKGROUND">Short-term and long-term exposure to prolonged sitting is associated with excess food intake and weight gain in children. Interrupting prolonged sitting with low-intensity activity has been shown to not alter hunger, satiety, or food consumption in children, however it is unclear whether interrupting sitting with high-intensity activity will alter appetite regulation in children.</AbstractText><AbstractText Label="PURPOSE">The purpose of this study was to examine the acute effects of interrupting prolonged sitting with intermittent activity performed at varying intensities on hunger, satiety, prospective food consumption (PFC), and food intake in preadolescent children.</AbstractText><AbstractText Label="METHODS">Thirty-nine children (ages 7-11 years, 54% female, 33% overweight/obese) completed four experimental conditions in random order: 8 hours of sitting interrupted with 20, 2-minute low-, moderate-, or high-intensity activity breaks or 20, 2-minute sedentary screen time breaks. Exercise intensity corresponded with 25%, 50% and 75% of heart rate reserve, respectively. Hunger, satiety, and PFC were assessed using the Visual Analog Scale, at five time points (pre- and post-breakfast, pre- and post-lunch, and pre-dinner) during each experimental condition. Dietary compensation was assessed as total caloric intake during a post-condition dinner standardized to provide 70% of estimated daily energy requirements.</AbstractText><AbstractText Label="RESULTS">There was a significant effect of time on hunger, satiety, and PFC throughout each condition day (p< 0.001). There were no differences across conditions for hunger (sedentary: 4.9±0.3 cm, low: 5.0±0.3 cm, moderate: 5.1±0.3 cm, high: 5.1±0.3 cm, p>0.05), satiety (sedentary: 4.7±0.3 cm, low: 4.4±0.3 cm, moderate: 4.6±0.3 cm, high: 4.2±0.3 cm, p>0.05), and PFC (sedentary: 4.9±0.3 cm, low: 4.7±0.3 cm, moderate: 4.9±0.3 cm, high: 5.0±0.3 cm, p>0.05). There were no significant differences in post-activity food intake across conditions (sedentary: 1071.9±53.6 kcals; low: 1092.6±43.4kcals; moderate: 996.2±54.6kcals; high: 1138.7±62.8kcals, p>0.05). However, there was a significant effect of condition on energy balance (sedentary: +61.4±65.9 kcals, low: +74.9±57.6 kcals, moderate: -58.3±62.8 kcals, high: -391.2±77.9 kcals; p<0.001). There were no significant effects of weight status on hunger, satiety, PFC, post-activity food intake, and mean energy balance across conditions (all p's>0.05).</AbstractText><AbstractText Label="CONCLUSIONS">Interrupting prolonged sitting with physical activity of any intensity does not alter appetite sensations and subsequent food consumption in children. These data suggest that interventions targeting prolonged sitting with high-intensity intermittent activity may be an effective strategy to increase physical activity energy expenditure without increasing food intake, allowing for a short-term energy deficit in both healthy weight and overweight/obese children. Future studies should examine the long-term effects of interrupting prolonged sitting with activity on food consumption and weight status in preadolescent children.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ajibewa</LastName><ForeName>Tiwaloluwa A</ForeName><Initials>TA</Initials><AffiliationInfo><Affiliation>University of Michigan School of Kinesiology, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Michigan Childhood Disparities Research Laboratory, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>O'Sullivan</LastName><ForeName>Molly P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>University of Michigan School of Kinesiology, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Michigan Childhood Disparities Research Laboratory, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nagy</LastName><ForeName>Matthew R</ForeName><Initials>MR</Initials><AffiliationInfo><Affiliation>University of Michigan School of Kinesiology, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Michigan Childhood Disparities Research Laboratory, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Block</LastName><ForeName>Shannon S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>University of Michigan Childhood Disparities Research Laboratory, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Robinson</LastName><ForeName>Leah E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>University of Michigan School of Kinesiology, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Colabianchi</LastName><ForeName>Natalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>University of Michigan School of Kinesiology, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hasson</LastName><ForeName>Rebecca E</ForeName><Initials>RE</Initials><Identifier Source="ORCID">0000-0003-4526-2656</Identifier><AffiliationInfo><Affiliation>University of Michigan School of Kinesiology, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Michigan Childhood Disparities Research Laboratory, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P30 DK089503</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>12</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000886" MajorTopicYN="N">Anthropometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001066" MajorTopicYN="Y">Appetite</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004435" MajorTopicYN="Y">Eating</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015444" MajorTopicYN="N">Exercise</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011187" MajorTopicYN="Y">Posture</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011795" MajorTopicYN="N">Surveys and Questionnaires</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement><b>Competing Interests: </b>The authors have declared that no competing interests exist.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>6</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>12</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>12</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>1</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29287061</ArticleId><ArticleId IdType="pmc">PMC5747427</ArticleId><ArticleId IdType="doi">10.1371/journal.pone.0188986</ArticleId><ArticleId IdType="pii">PONE-D-17-21528</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Saunders TJ, Chaput JP, Goldfield GS, Colley RC, Kenny GP, Doucet E, et al. 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Energy expenditure compared to physical activity measured by accelerometry and self-report in adolescents: a validation study. PLoS One. 2013.
November
4;8(11):e77036
doi: 10.1371/journal.pone.0077036
</Citation><ArticleIdList><ArticleId IdType="doi">10.1371/journal.pone.0077036</ArticleId><ArticleId IdType="pmc">PMC3817188</ArticleId><ArticleId IdType="pubmed">24223707</ArticleId></ArticleIdList></Reference><Reference><Citation>Karvonen MJ, Kentala E, Mustala O. The effects of training on heart rate; a longitudinal study. In Annales medicinae experimentalis et biologiae Fenniae 1957. (Vol. 35, No. 3, p. 307).</Citation><ArticleIdList><ArticleId IdType="pubmed">13470504</ArticleId></ArticleIdList></Reference><Reference><Citation>Duncan MJ, Clarke ND, Birch SL, Tallis J, Hankey J, Bryant E, et al.
The effect of green exercise on blood pressure, heart rate and mood state in primary school children. International journal of environmental research and public health. 2014.
April
2;11(4):3678–88. doi: 10.3390/ijerph110403678
</Citation><ArticleIdList><ArticleId IdType="doi">10.3390/ijerph110403678</ArticleId><ArticleId IdType="pmc">PMC4025002</ArticleId><ArticleId IdType="pubmed">24699030</ArticleId></ArticleIdList></Reference><Reference><Citation>Ridgers ND, Stratton G, Clark E, Fairclough SJ, Richardson DJ. Day-to-day and seasonal variability of physical activity during school recess. Preventive Medicine. 2006.
May
31;42(5):372–4. doi: 10.1016/j.ypmed.2006.01.017
</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ypmed.2006.01.017</ArticleId><ArticleId IdType="pubmed">16510176</ArticleId></ArticleIdList></Reference><Reference><Citation>Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Medicine and science in sports and exercise. 2000. September 1;32(9; SUPP/1):S498–504.</Citation><ArticleIdList><ArticleId IdType="pubmed">10993420</ArticleId></ArticleIdList></Reference><Reference><Citation>Arvaniti K, Richard D, Tremblay A. Reproducibility of energy and macronutrient intake and related substrate oxidation rates in a buffet-type meal. British journal of nutrition. 2000. May;83(5):489–95.</Citation><ArticleIdList><ArticleId IdType="pubmed">10953673</ArticleId></ArticleIdList></Reference><Reference><Citation>Block SS, Tooley TR, Nagy MR, O’Sullivan MP, Hasson RE. Cognitive responses to intermittent physical activity in elementary school-age children. Medicine and science in sports and exercise. 2016. Volume 48(5 SUPP/1):638.</Citation></Reference><Reference><Citation>Chaput JP, Klingenberg L, Astrup A, Sjödin AM. Modern sedentary activities promote overconsumption of food in our current obesogenic environment. Obesity Reviews. 2011.
May
1;12(5):e12–20. doi: 10.1111/j.1467-789X.2010.00772.x
</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1467-789X.2010.00772.x</ArticleId><ArticleId IdType="pubmed">20576006</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang YC, Gortmaker SL, Sobol AM, Kuntz KM. Estimating the energy gap among US children: a counterfactual approach. Pediatrics. 2006.
December
1;118(6):e1721–33. doi: 10.1542/peds.2006-0682
</Citation><ArticleIdList><ArticleId IdType="doi">10.1542/peds.2006-0682</ArticleId><ArticleId IdType="pubmed">17142497</ArticleId></ArticleIdList></Reference><Reference><Citation>Allsop S, Dodd-Reynolds CJ, Green BP, Debuse D, Rumbold PL. Acute effects of active gaming on ad libitum energy intake and appetite sensations of 8–11-year-old boys. British Journal of Nutrition. 2015.
December
28;114(12):2148–55. doi: 10.1017/S0007114515003724
</Citation><ArticleIdList><ArticleId IdType="doi">10.1017/S0007114515003724</ArticleId><ArticleId IdType="pubmed">26435259</ArticleId></ArticleIdList></Reference><Reference><Citation>Fisher JO, Arreola A, Birch LL, Rolls BJ. Portion size effects on daily energy intake in low-income Hispanic and African American children and their mothers. The American journal of clinical nutrition. 2007. December 1;86(6):1709–16.</Citation><ArticleIdList><ArticleId IdType="pubmed">18065590</ArticleId></ArticleIdList></Reference><Reference><Citation>Geier AB, Rozin P, Doros G. Unit bias: A new heuristic that helps explain the effect of portion size on food intake. Psychological Science. 2006.
June;17(6):521–5. doi: 10.1111/j.1467-9280.2006.01738.x
</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/j.1467-9280.2006.01738.x</ArticleId><ArticleId IdType="pubmed">16771803</ArticleId></ArticleIdList></Reference><Reference><Citation>Hills AP, Mokhtar N, Byrne NM. Assessment of physical activity and energy expenditure: an overview of objective measures. Frontiers in nutrition. 2014.
June
16;1:5
doi: 10.3389/fnut.2014.00005
</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fnut.2014.00005</ArticleId><ArticleId IdType="pmc">PMC4428382</ArticleId><ArticleId IdType="pubmed">25988109</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29286395</PMID><DateCompleted><Year>2018</Year><Month>06</Month><Day>15</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>11</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>130</Issue><PubDate><Year>2017</Year><Month>Dec</Month><Day>11</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing.
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It is now well recognized that heart failure (HF) patients with left bundle branch block (LBBB) derive substantial clinical benefits from cardiac resynchronization therapy (CRT), and LBBB has become one of the important predictors for CRT response. The conventional tachypacing-induced HF model has several major limitations, including absence of stable LBBB and rapid reversal of left ventricular (LV) dysfunction after cessation of pacing. Hence, it is essential to establish an optimal model of chronic HF with isolated LBBB for studying CRT benefits. In the present study, a canine model of asynchronous HF induced by left bundle branch (LBB) ablation and 4 weeks of rapid right ventricular (RV) pacing is established. The RV and right atrial (RA) pacing electrodes via the jugular vein approach, together with an epicardial LV pacing electrode, were implanted for CRT performance. Presented here are the detailed protocols of radiofrequency (RF) catheter ablation, pacing leads implantation, and rapid pacing strategy. Intracardiac and surface electrograms during operation were also provided for a better understanding of LBB ablation. Two-dimensional speckle tracking imaging and aortic velocity time integral (aVTI) were acquired to validate the chronic stable HF model with LV asynchrony and CRT benefits. By coordinating ventricular activation and contraction, CRT uniformed the LV mechanical work and restored LV pump function, which was followed by reversal of LV dilation. Moreover, the histopathological study revealed a significant restoration of cardiomyocyte diameter and collagen volume fraction (CVF) after CRT performance, indicating a histologic and cellular reverse remodeling elicited by CRT. In this report, we described a feasible and valid method to develop a chronic asynchronous HF model, which was suitable for studying structural and biologic reverse remodeling following CRT.
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2,335,051 |
To Compare the Effects of Different Doses of Dexmedetomidine on Intrathecal Bupivacaine in Infraumbilical Surgeries: A Prospective, Randomized, Double-blind Clinical Study.
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Spinal anesthesia is preferred technique of choice in infraumbalical surgeries. Limitation of this technique is shorter duration of analgesia, so various adjuvants have been used with intrathecal bupivacaine such as fentanyl, clonidine, and dexmedetomidine. Dexmedetomidine is a highly selective alpha 2 adrenergic agonist. The aim of our study was to know the effect of different doses of dexmedetomidine on intrathecal bupivacaine.</AbstractText>The prospective, randomized, double-blind study was conducted in tertiary health care center, on ninety patients of the American Society of Anesthesiology Class I and II, of age group 18-60 years of either sex. They were randomly allocated into three groups. Group BD5</sub> (n</i> = 30): intrathecal bupivacaine 12.5 mg (2.5 ml) + dexmedetomidine 5 μg (0.5 ml), Group BD10</sub> (n</i> = 30): intrathecal bupivacaine 12.5 mg (2.5 ml) + dexmedetomidine 10 μg (0.5 ml), Group BD15</sub> (n</i> = 30): intrathecal bupivacaine 12.5 mg (2.5 ml) + dexmedetomidine 15 μg (0.5 ml) administered intarthecally. The onset and maximum level of sensory block, time to reach maximum level of sensory block, time of two-segment sensory regression, the total duration analgesia, time of rescue analgesia, onset and duration of motor block and heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, respiratory rate, and oxygen saturation were recorded at various intervals. Moreover, any adverse effects such as bradycardia, hypotension, nausea, vomiting, and sedation were recorded.</AbstractText>The onset time of sensory block in Group D5</sub>-2.76 ± 1.32, Group D10</sub>-2.45 ± 1.50, and Group D15</sub>-1.86±0.93, which is statistically significant (P</i> = 0.025). The time taken for two-segment sensory regression Group D5</sub>-96.66 ± 33.67, Group D10</sub>-116.80 ± 36.27, and Group D15</sub> 120.96 ± 30.24, (P</i> = 0.014). The time taken for complete sensory recovery in Group D5</sub>-319.83 ± 61.41, Group D10</sub>-336.13 ± 61.38, and Group D15</sub>-415.20 ± 96.6, which is statistically highly significant (P</i> = 0.000). Time for rescue analgesia in Group D5</sub>-377.46 ± 60.05, in Group D10</sub>-401.60 ± 61.11, and in Group D15</sub>-517.96 ± 97.30, which is statistically highly significant (P</i> < 0.000).</AbstractText>We concluded that there was decrease in onset of sensory and motor blockade with the prolongation of duration of anesthesia and analgesia in a dose-dependent manner.</AbstractText>
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2,335,052 |
Promoting Recruitment using Information Management Efficiently (PRIME): a stepped-wedge, cluster randomised trial of a complex recruitment intervention embedded within the REstart or Stop Antithrombotics Randomised Trial.
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Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART.</AbstractText><AbstractText Label="METHODS/DESIGN" NlmCategory="METHODS">We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate.</AbstractText>We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to have been randomised using the audit reports. Respondents frequently reported resource and time pressures as being key barriers to running the audit reports.</AbstractText>The PRIME complex intervention did not significantly improve the recruitment rate to RESTART. Further research is needed to establish if PRIME might be beneficial at an earlier stage in a prevention trial or for prevention dilemmas that arise more often in clinical practice.</AbstractText>
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2,335,053 |
Normal interventricular differences in tissue architecture underlie right ventricular susceptibility to conduction abnormalities in a mouse model of Brugada syndrome.
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Loss-of-function of the cardiac sodium channel NaV1.5 is a common feature of Brugada syndrome. Arrhythmias arise preferentially from the right ventricle (RV) despite equivalent NaV1.5 downregulation in the left ventricle (LV). The reasons for increased RV sensitivity to NaV1.5 loss-of-function mutations remain unclear. Because ventricular electrical activation occurs predominantly in the transmural axis, we compare RV and LV transmural electrophysiology to determine the underlying cause of the asymmetrical conduction abnormalities in Scn5a haploinsufficient mice (Scn5a+/-).</AbstractText>Optical mapping and two-photon microscopy in isolated-perfused mouse hearts demonstrated equivalent depression of transmural conduction velocity (CV) in the LV and RV of Scn5a+/- vs. wild-type littermates. Only RV transmural conduction was further impaired when challenged with increased pacing frequencies. Epicardial dispersion of activation and beat-to-beat variation in activation time were increased only in the RV of Scn5a+/- hearts. Analysis of confocal and histological images revealed larger intramural clefts between cardiomyocyte layers in the RV vs. LV, independent of genotype. Acute sodium current inhibition in wild type hearts using tetrodotoxin reproduced beat-to-beat activation variability and frequency-dependent CV slowing in the RV only, with the LV unaffected. The influence of clefts on conduction was examined using a two-dimensional monodomain computational model. When peak sodium channel conductance was reduced to 50% of normal the presence of clefts between cardiomyocyte layers reproduced the activation variability and conduction phenotype observed experimentally.</AbstractText>Normal structural heterogeneities present in the RV are responsible for increased vulnerability to conduction slowing in the presence of reduced sodium channel function. Heterogeneous conduction slowing seen in the RV will predispose to functional block and the initiation of re-entrant ventricular arrhythmias.</AbstractText>
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2,335,054 |
Modulation of sympathetic vasoconstriction is critical for the effects of sleep on arterial pressure in mice.
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While values of arterial pressure during sleep are predictive of cardiovascular risk, the autonomic mechanisms underlying the cardiovascular effects of sleep remain poorly understood. Here, we assess the autonomic mechanisms of the cardiovascular effects of sleep in C57Bl/6J mice, taking advantage of a novel technique for continuous intraperitoneal infusion of autonomic blockers. Our results indicate that non-REM sleep decreases arterial pressure by decreasing sympathetic vasoconstriction, decreases heart rate by balancing parasympathetic activation and sympathetic withdrawal, and increases cardiac baroreflex sensitivity mainly by increasing fluctuations in parasympathetic activity. Our results also indicate that REM sleep increases arterial pressure by increasing sympathetic activity to the heart and blood vessels, and increases heart rate, at least in part, by increasing cardiac sympathetic activity. These results provide a framework for generating and testing hypotheses on cardiovascular derangements during sleep in mouse models and human patients.</AbstractText>The values of arterial pressure (AP) during sleep predict cardiovascular risk. Sleep exerts similar effects on cardiovascular control in human subjects and mice. We aimed to determine the underlying autonomic mechanisms in 12 C57Bl/6J mice with a novel technique of intraperitoneal infusion of autonomic blockers, while monitoring the electroencephalogram, electromyogram, AP and heart period (HP, i.e. 1/heart rate). In different sessions, we administered atropine methyl nitrate, atenolol and prazosin to block muscarinic cholinergic, β1</sub> -adrenergic and α1</sub> -adrenergic receptors, respectively, and compared each drug infusion with a matched vehicle infusion. The decrease in AP from wakefulness to non-rapid-eye-movement sleep (N) was abolished by prazosin but was not significantly affected by atropine and atenolol, which, however, blunted the accompanying increase in HP to a similar extent. On passing from N to rapid-eye-movement sleep (R), the increase in AP was significantly blunted by prazosin and atenolol, whereas the accompanying decrease in HP was blunted by atropine and abolished by atenolol. Cardiac baroreflex sensitivity (cBRS, sequence technique) was dramatically decreased by atropine and slightly increased by prazosin. These data indicate that in C57Bl/6J mice, N decreases mean AP by decreasing sympathetic vasoconstriction, increases HP by balancing parasympathetic activation and sympathetic withdrawal, and increases cBRS mainly by increasing fluctuations in parasympathetic activity. R increases mean AP by increasing sympathetic vasoconstriction and cardiac sympathetic activity, which also explains, at least in part, the concomitant decrease in HP. These data represent the first comprehensive assessment of the autonomic mechanisms of cardiovascular control during sleep in mice.</AbstractText>© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.</CopyrightInformation>
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2,335,055 |
Permutations of functional magnetic resonance imaging classification may not be normally distributed.
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A fundamental question that often occurs in statistical tests is the normality of distributions. Countless distributions exist in science and life, but one distribution that is obtained via permutations, usually referred to as permutation distribution, is interesting. Although a permutation distribution should behave in accord with the central limit theorem, if both the independence condition and the identical distribution condition are fulfilled, no studies have corroborated this concurrence in functional magnetic resonance imaging data. In this work, we used Anderson-Darling test to evaluate the accordance level of permutation distributions of classification accuracies to normality expected under central limit theorem. A simulation study has been carried out using functional magnetic resonance imaging data collected, while human subjects responded to visual stimulation paradigms. Two scrambling schemes are evaluated: the first based on permuting both the training and the testing sets and the second on permuting only the testing set. The results showed that, while a normal distribution does not adequately fit to permutation distributions most of the times, it tends to be quite well acceptable when mean classification accuracies averaged over a set of different classifiers is considered. The results also showed that permutation distributions can be probabilistically affected by performing motion correction to functional magnetic resonance imaging data, and thus may weaken the approximation of permutation distributions to a normal law. Such findings, however, have no relation to univariate/univoxel analysis of functional magnetic resonance imaging data. Overall, the results revealed a strong dependence across the folds of cross-validation and across functional magnetic resonance imaging runs and that may hinder the reliability of using cross-validation. The obtained p-values and the drawn confidence level intervals exhibited beyond doubt that different permutation schemes may beget different permutation distributions as well as different levels of accord with central limit theorem. We also found that different permutation schemes can lead to different permutation distributions and that may lead to different assessment of the statistical significance of classification accuracy.
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2,335,056 |
miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11.
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Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue, we selected miR-200a-5p and its target gene ring finger protein 11 (RNF11) based on differential expression in cardiac tissue and confirmed the relationship between miR-200a-5p and RNF11 by dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR) in cardiomyocytes. We further explored the function of miR-200a-5p and observed that overexpression of miR-200a-5p spark the receptor interacting serine/threonine kinase 3 (RIP3)-dependent necroptosis in vivo and in vitro. To understand whether miR-200a-5p and RNF11 are involved in the RIP3-dependent necroptosis pathway, we presumed that oxidative stress, inflammation response and the mitogen-activated protein kinase (MAPK) pathway might trigger necroptosis. Interestingly, necroptosis trigger, z-VAD-fmk, failed to induce necroptosis but enhanced cell survival against necrosis in cardiomyocytes with knockdown of miR-200a-5p. Our present study provides a new insight that the modulation of miR-200a-5p and its target gene might block necroptosis in the heart, revealing a novel myocardial necrosis regulation model in heart disease.
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2,335,057 |
Efficacy of pudendal nerve block for alleviation of catheter-related bladder discomfort in male patients undergoing lower urinary tract surgeries: A randomized, controlled, double-blind trial.
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Catheter-related bladder discomfort (CRBD) to an indwelling urinary catheter is defined as a painful urethral discomfort, resistant to conventional opioid therapy, decreasing the quality of postoperative recovery. According to anatomy, the branches of sacral somatic nerves form the afferent nerves of the urethra and bladder triangle, which deriving from the ventral rami of the second to fourth sacral spinal nerves, innervating the urethral muscles and sphincter of the perineum and pelvic floor; as well as providing sensation to the penis and clitoris in males and females, which including the urethra and bladder triangle. Based on this theoretical knowledge, we formed a hypothesis that CRBD could be prevented by pudendal nerve block.</AbstractText>To evaluate if bilateral nerve stimulator-guided pudendal nerve block could relieve CRBD through urethra discomfort alleviation.</AbstractText>Single-center randomized parallel controlled, double blind trial conducted at West China Hospital, Sichuan University, China.</AbstractText>One hundred and eighty 2 male adult patients under general anesthesia undergoing elective trans-urethral resection of prostate (TURP) or trans-urethral resection of bladder tumor (TURBT). Around 4 out of 182 were excluded, 178 patients were randomly allocated into pudendal and control groups, using computer-generated randomized numbers in a sealed envelope method. A total of 175 patients completed the study.</AbstractText>Pudendal group received general anesthesia along with nerve-stimulator-guided bilateral pudendal nerve block and control group received general anesthesia only.</AbstractText>Incidence and severity of CRBD; and postoperative VAS score of pain.</AbstractText>CRBD incidences were significantly lower in pudendal group at 30 minutes (63% vs 82%, P = .004), 2 hours (64% vs 90%, P < .000), 8 hours (58% vs 79%, P = .003) and 12 hours (52% vs 69%, P = .028) also significantly lower incidence of moderate to severe CRBD in pudendal group at 30 minutes (29% vs 57%, P < .001), 2 hours (22% vs 55%, P < .000), 8 hours (8% vs 27%, P = .001) and 12 hours (6% vs 16%, P = .035) postoperatively. The postoperative pain score in pudendal group was lower at 30 minutes (P = .003), 2 hours (P < .001), 8 hours (P < .001), and 12 hours (P < .001), with lower heart rate and mean blood pressure. One patient complained about weakness in levator ani muscle.</AbstractText>General anesthesia along with bilateral pudendal nerve block decreased the incidence and severity of CRBD for the first 12 hours postoperatively.</AbstractText>
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2,335,058 |
Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.
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CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC<sub>50</sub> = 0.02-10.5 nM), along with lower hERG inhibition (IC<sub>50</sub> > 30 μM, ∼10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug.
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2,335,059 |
Superior Efficacy of Lipid Emulsion Infusion Over Serum Alkalinization in Reversing Amitriptyline-Induced Cardiotoxicity in Guinea Pig.
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Tricyclic antidepressants (TCAs) are a major cause of fatal drug poisoning due to their cardiotoxicity. Alkalinization by sodium bicarbonate (NaHCO3) administration, the first-line therapy for TCA-induced cardiotoxicity, can occasionally yield insufficient efficacy in severe cases. Because most TCAs are highly lipophilic, lipid emulsion may be more effective than alkalinization. However, it remains to be determined whether lipid emulsion is more beneficial than alkalinization in reversing amitriptyline-induced cardiotoxicity.</AbstractText>Hemodynamic variables were recorded from in vivo guinea pig models and Langendorff-perfused hearts. Whole-cell patch-clamp experiments were conducted on enzymatically isolated ventricular cardiomyocytes to record fast sodium currents (INa). Lipid solutions were prepared using 20% Intralipid. The pH of the alkaline solution was set at 7.55. We assessed the effect of lipid emulsion on reversing amitriptyline-induced cardiotoxicity, in vivo and in vitro, compared to alkalinization. The data were evaluated by Student t test, 1-way repeated-measures analysis of variance, or analysis of covariance (covariate = amitriptyline concentration); we considered data statistically significant when P < .05.</AbstractText>In the in vivo model, intervention with lipids significantly reversed the amitriptyline-induced depression of mean arterial pressure and prolongation of QRS duration on electrocardiogram more than alkalinization (mean arterial pressure, mean difference [95% confidence interval]: 19.0 mm Hg [8.5-29.4]; QRS duration, mean difference [95% confidence interval] -12.0 milliseconds [-16.1 to -7.8]). In the Langendorff experiments, perfusion with 1% and 2% lipid solutions demonstrated significant recovery in left ventricular developed pressure (LVdevP), maximum change rate of increase of LVdevP (dP/dtmax) and rate-pressure product compared with alkaline solution (LVdevP [mm Hg], alkaline 57 ± 35, 1% lipid 94 ± 12, 2% lipid 110 ± 14; dP/dtmax [mm Hg/s], alkaline 748 ± 441, 1% lipid 1502 ± 334, 2% lipid 1753 ± 389; rate-pressure product [mm Hg·beats·minute], alkaline 11,214 ± 8272, 1% lipid 19,025 ± 8427, 2% lipid 25,261 ± 4803 with analysis of covariance). Furthermore, lipid solutions (0.5%-4%) resulted in greater recovery of hemodynamic parameters at 3 μM amitriptyline. Amitriptyline inhibited INa in a dose-dependent manner: the half-maximal inhibitory concentration (IC50) was 0.39 μM. The IC50 increased to 0.75 μM in the alkaline solution, 3.2 μM in 1% lipid solution, and 6.1 μM in 2% lipid solution. Furthermore, the lipid solution attenuated the use-dependent block of sodium channels by amitriptyline more than alkaline solution. On 30 consecutive pulses at 1 Hz, the current decreased to 50.1 ± 2.1, 60.3 ± 1.9, and 90.4% ± 1.8% in standard, alkaline, and 1% lipid solution, respectively. Even 0.5% lipid solution showed greater effects than the alkaline solution in all experiments.</AbstractText>Lipid emulsion significantly suppressed amitriptyline-induced INa, inhibition, which was likely related to the marked improvement in hemodynamic status observed in vivo and in isolated perfused hearts. These results suggest the superiority of lipid emulsion as the first-line therapy for TCA-induced cardiotoxicity compared to alkalinization therapy.</AbstractText>
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2,335,060 |
Spatial-temporal analysis of prostate cancer incidence from the Pennsylvania Cancer Registry, 2000-2011.
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Prostate cancer is the most common cancer diagnosed among males, and the incidence in Pennsylvania, USA is considerably higher than nationally. Knowledge of regional differences and time trends in prostate cancer incidence may contribute to a better understanding of aetiologic factors and racial disparities in outcomes, and to improvements in preventive intervention and screening efforts. We used Pennsylvania Cancer Registry data on reported prostate cancer diagnoses between 2000 and 2011 to study the regional distribution and temporal trends of prostate cancer incidence in both Pennsylvania White males and Philadelphia metropolitan area Black males. For White males, we generated and mapped county-specific age-adjusted incidence and standardised incidence ratios by period cohort, and identified spatial autocorrelation and local clusters. In addition, we fitted Bayesian hierarchical generalised linear Poisson models to describe the temporal and aging effects separately in Whites state-wide and metropolitan Philadelphia blacks. Incidences of prostate cancer among white males declined from 2000-2002 to 2009-2011 with an increasing trend to some extent in the period 2006-2008 and significant variation across geographic regions, but less variation exists for metropolitan Philadelphia including majority of Black patients. No significant aging effect was detected for White and Black men, and the peak age group for prostate cancer risk varied by race. Future research should seek to identify potential social and environmental risk factors associated with geographical/racial disparities in prostate cancer. As such, there is a need for more effective surveillance so as to detect, reduce and control the cancer burden associated with prostate cancer.
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2,335,061 |
Variability of nutrients intake, lipid profile and cardiovascular mortality among geographical areas in Spain: The DRECE study.
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It has often been suggested that cardiovascular mortality and their geographical heterogeneity are associated with nutrients intake patterns and also lipid profile. The large Spanish study Dieta y Riesgo de Enfermedades Cardiovasculares en España (DRECE) investigated this theory from 1991 to 2010. Out of the 4,783 Spanish individuals making up the DRECE cohort, 220 subjects (148 men and 72 women) died (4.62%) during the course of the study. The mean age of patients who died from cardiovascular causes (32 in all) was 61.08 years 95% CI (57.47-64.69) and 70.91% of them were males. The consumption of nutrients and the lipid profile by geographical area, studied by geospatial models, showed that the east and southern area of the country had the highest fat intake coupled to a high rate of unhealthy lipid profile. It was concluded that the spatial geographical analysis showed a relationship between high fat intake, unhealthy lipid profile and cardiovascular mortality in the different geographical areas, with a high variability within the country.
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2,335,062 |
Influence of Competitive-Anxiety on Heart Rate Variability in Swimmers.
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The aim of this study was to analyze the relationship between competitive anxiety and heart rate variability (HRV) in swimming athletes. A total of 66 volunteers (41 male and 27 female) who swam the 400-m freestyle in the Brazilian Swimming Championships participated. Thirty minutes before the 400-m freestyle event, the athletes answered the Competitive Anxiety Inventory (CSAI-2R) questionnaire, then underwent anthropometric (body weight, height, and skinfold thickness) and HRV measurements. Then, at a second meeting, held 3 h after the 400-m freestyle event, the athletes returned to the evaluation room for HRV measurement (Polar<sup>®</sup> RS800cx, Kempele, Finland). Multiple linear regression was used to evaluate the relationship between competitive anxiety and HRV. The multiple linear regression was performed in three blocks (block 1: cognitive anxiety, block 2: somatic anxiety, and block 3: self-confidence), adopting the forward model. The results indicated a significant association between cognitive anxiety (p = 0.001) and HRV. An increased magnitude of the association was observed when somatic anxiety was inserted in the model (p = 0.001). In contrast, self-confidence showed, which was inserted in block 3, no relationship with HRV (p = 0.27). It was concluded that cognitive and somatic anxieties were associated with the HRV of swimmers. Athletes with a high magnitude of cognitive and/or somatic anxiety demonstrated more significant autonomic nervous system disturbance. Practically, psychological interventions are needed to improve anxiety states that are specific to perform well, and to improve HRV.
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2,335,063 |
[Effects of tooth extraction under acupuncture anesthesia].
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To compare the effects for tooth extraction between acupuncture anesthesia and drug local block anesthesia.</AbstractText>Sixty patients were randomly assigned into an acupuncture group and a drug group, 30 cases in each one. Acupuncture was applied at Hegu (LI 4), Neiting (ST 44) and the affected side Xiaguan (ST 7), and Jiache (ST 6), etc. Arrachement was used after deqi</i> and the needles were retained for 10 min after tooth extraction in the acupuncture group. Compound articaine hydrochloride injection was used to conventional local anesthesia, after which tooth extraction was implemented in the drug group. The effects of anesthesia and analgesia were compared between the two groups with pain rating index (PRI) and visual analogue scale (VAS). Besides, the bleeding amounts and adverse reaction rates during the operation and the blood pressure, pulse, and respiration before and after operation were observed.</AbstractText>Tooth extraction was completed, and the excellent rates, PRI and VAS scores were not significantly different in the two groups (all P</i>>0.05). The bleeding amounts and adverse reaction rates in the acupuncture group were lower than those in the drug group (P</i><0.01, P</i><0.05).The blood pressure, pulse and respiratory during surgery remained normal without significance between the two groups (all P</i>>0.05).</AbstractText>The effect of acupuncture anesthesia for tooth extraction is equal to that of drug anesthesia. Its analgesia is complete with stable vital signs and less adverse reactions. It is worthy of popularizing.</AbstractText>
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2,335,064 |
History-driven population structure and asymmetric gene flow in a recovering large carnivore at the rear-edge of its European range.
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Understanding the mechanisms and patterns involved in population recoveries is challenging and important in shaping conservation strategies. We used a recovering rear-edge population of brown bears at their southernmost European range in Greece as a case study (2007-2010) to explore the recovery genetics at a species' distribution edge. We used 17 microsatellite and a mitochondrial markers to evaluate genetic structure, estimate effective population size and genetic diversity, and infer gene flow between the identified subpopulations. To understand the larger picture, we also compared the observed genetic diversity of each subpopulation with other brown bear populations in the region. The results indicate that the levels of genetic diversity for bears in western Greece are the lowest recorded in southeastern Europe, but still higher than those of other genetically depauperate bear populations. Apart from a complete separation of bear populations in eastern and western Greece, our results also indicate a considerable genetic sub-structuring in the West. As bear populations in Greece are now recovering, this structure is dissolving through a "recovery cascade" of asymmetric gene flow from South to North between neighboring subpopulations, mediated mainly by males. Our study outlines the importance of small, persisting populations, which can act as "stepping stones" that enable a rapid population expansion and recovery. This in turn makes their importance much greater than their numeric or genetic contribution to a species as a whole.
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2,335,065 |
Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome.
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Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a high prevalence in females of childbearing age. Pregnancy in SLE nowadays has favorable outcomes for the majority of women. However, flares of disease activity, preeclampsia, fetal loss, and preterm birth are well-known risks in such pregnancies. Anti-SS-A(Ro)/SS-B(La) antibodies put fetuses at risk for congenital heart block and neonatal lupus. Several risk factors for adverse pregnancy outcomes have been identified. Women with antiphospholipid antibodies or antiphospholipid syndrome and lupus nephritis represent a group with high risk for obstetric complications. Factors such as appropriate preconception counseling and medication adjustment, strict disease control prior to pregnancy, and intensive surveillance during and after pregnancy are essential to improve pregnancy outcome. The aim of this review article is to update on the medical care of pregnancy in these women to ensure the best maternal and fetal prognosis.
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2,335,066 |
A comparison of haemodynamic responses between clinical assessment-guided tracheal intubation and neuromuscular block monitoring-guided tracheal intubation: A prospective, randomised study.
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Haemodynamic responses to laryngoscopy and endotracheal intubation and their hazards are well documented. The purpose of the study was to compare the effects of laryngoscopy and intubation on cardiovascular responses when the appropriate moment for intubation was directed by either clinical judgment or train-of-four assessment.</AbstractText>A total of 68 patients, posted for laparoscopic cholecystectomy, were randomised into two groups. In Group M patients, the trachea was intubated after train of four counts became zero in adductor pollicis muscle, whereas in Group C patients, the trachea was intubated after the clinical judgment of jaw muscle relaxation. Changes in heart rate (HR) and mean arterial pressure, intubating conditions and the time between the administration of a neuromuscular blocking agent and endotracheal intubation were recorded. Results were analysed by the Analysis of variance and chi-square tests.</AbstractText>HR and mean arterial pressure were significantly higher in Group C as compared to Group M after laryngoscopy and tracheal intubation (P</i> < 0.05). The mean time required for intubation was significantly shorter in Group C compared to Group M (175 ± 7 s vs. 385 ± 101 s). Excellent and good intubation conditions were observed in all Group M patients, whereas 24 out of 34 patients (70%) in Group C showed excellent and good intubation conditions.</AbstractText>Haemodynamic responses to laryngoscopy and tracheal intubation can be significantly attenuated if tracheal intubation is performed following complete paralysis of laryngeal muscles, detected by neuromuscular monitoring of adductor pollicis muscle.</AbstractText>
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2,335,067 |
Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial.
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Therapy with elastic compression stockings has been the cornerstone for prevention of post-thrombotic syndrome for decades in patients after acute deep venous thrombosis. It is uncertain who benefits most from therapy, and what the optimum duration of therapy should be. We therefore aimed to assess the safety and efficacy of individualised duration of compression therapy versus the standard duration of 24 months following an initial treatment period of 6 months.</AbstractText>We did a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the leg and without pre-existent venous insufficiency (Clinical Etiological Anatomical and Pathophysiological score <C3) to receive either individualised duration of elastic compression therapy or standard duration of therapy for 24 months following an initial treatment period of 6 months. Randomisation was done with a web-based automatic randomisation programme (TENALEA) and a random block size (2-12), and was stratified by centre, age, and body-mass index. In the initial phase, compression was applied within 24 h of diagnosis according to three prespecified protocols. All patients received elastic compression stockings (30-40 mm Hg) for 6 months, and were instructed to wear them every day during ambulant hours. Thereafter treatment was tailored on the basis of clinical signs and symptoms scored according to the Villalta post-thrombotic syndrome scale; patients assigned to individualised therapy with two consecutive Villalta scores of 4 or less were instructed to stop using the stockings. Patients were followed up for 2 years and assessed at five clinic visits at study inclusion, and 3, 6, 12, and 24 months after diagnosis (stocking allocation was not revealed to the assessors). The primary outcome was the proportion of patients with post-thrombotic syndrome at 24 months diagnosed according to original Villalta criteria (a score of ≥5 on two consecutive occasions at least 3 months apart) assessed by intention to treat. The predefined non-inferiority margin for the difference in success rates was set at 7·5%. This study has been completed and is registered with ClinicalTrials.gov, number NCT01429714.</AbstractText>Between March 22, 2011, and July 1, 2015, we enrolled 865 patients and randomly assigned 437 to individualised duration compression stockings and 428 to standard duration. 283 (66%) of 432 patients in the intervention group were advised before 24 months to stop wearing elastic compression stockings (236 [55%] of 432 patients after 6 months, and 47 [11%] of 432 at 12 months). Post-thrombotic syndrome occurred in 125 (29%) of 432 patients receiving individualised duration of therapy and in 118 (28%) of 424 receiving standard duration of therapy (odds ratio for difference 1·06, 95% CI 0·78 to 1·44). The absolute difference was 1·1% (95% CI -5·2 to 7·3), thus meeting the non-inferiority margin. 24 patients died, 17 (4%) in the individualised treatment group and seven (2%) in the standard duration group, but no deaths were related to treatment. No serious adverse events related to the intervention occurred.</AbstractText>Individualised therapy with elastic compression stockings for the prevention of post-thrombotic syndrome was non-inferior to standard duration of therapy of 24 months. Individualising the duration is effective and could shorten the length of therapy needed, potentially enhancing patients' wellbeing.</AbstractText>ZonMw (Netherlands).</AbstractText>Copyright © 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,068 |
Comparison of the effect of different infusion rates of sufentanil on surgical stress index during cranial pinning in children under general anaesthesia: a randomized controlled study.
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Surgical stress index (SSI) is an established indicator for intraoperative nociception. Opioids are used to block stimulus of cranial pinning in neurosurgery. We investigated the effect of different infusion rates of sufentanil on SSI during cranial pinning in children under general anaesthesia.</AbstractText>Forty-nine children (2-12 years of age) underwent neurosurgery with pinning. The children were randomized into three groups based on the rate of sufentanil infusion: 0.2, 0.5, and 0.8 μg·kg-1</sup>·hr.-1</sup>. Continuous sufentanil infusion began following neuromuscular blockade administration, at a rate determined by each patient's assigned treatment group. Following preparation for surgery, cranial pinning was performed. Systolic, diastolic, and mean blood pressures, along with heart rate and photoplethysmographic data, were continuously recorded from 1 min prior to cranial pinning through 5 min after cranial pinning, in 1-min intervals. SSI was calculated following the completion of surgery. Differences in measured outcomes over time among the three groups were evaluated using a generalized estimation equation. Differences in pinning outcomes in the same group were evaluated with Freidman test.</AbstractText>We found no statistical differences in long-term SSI that were associated with different infusion rates of sufentanil during cranial pinning. Blood pressures in all groups increased for 2 min after cranial pinning, and then decreased; we found no statistical difference in long-term blood pressure values among the groups. Heart rate increased after pinning in the group that received a low-dose infusion of sufentanil.</AbstractText>Since SSI was intended to measure the blunting effects of sufentanil towards the noxious stimulus of cranial pinning, our results suggest that SSI might not be sufficiently sensitive to monitor the nociceptive response in children.</AbstractText>( KCT0000978 , Jan-07, 2014).</AbstractText>
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2,335,069 |
Physiologically Triggered Digital Cognitive Aid Facilitates Crisis Management in a Simulated Operating Room: A Randomized Controlled Study.
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Although the benefits of using cognitive aids in anesthesia care have previously been demonstrated, several challenges remain. It must be presented in a timely manner, and providers must be amenable to using the tool once it is available. We hypothesized that anesthesia residents would perform superiorly when presented with a digital cognitive aid (DCogA) that is automatically triggered by a set vital sign aberration.</AbstractText>Thirty anesthesia residents were randomized to either control (with access to hard copy of the cognitive aid) or receive a DCogA projected on their anesthesia information management system with the onset of heart block and associated hypotension. The scenario ended upon commencement of pacing, and the times to interventions were recorded.</AbstractText>Fourteen participants were randomized to the control group and 16 to the intervention group DCogA. In the control group, 6 of 14 participants failed to pace, and in the DCogA group, all participants initiated pacing (P < 0.01). Those in the DCogA group were also faster to pace [260.1 (137.5) s vs. 405.1 (201.8) s, P = 0.03]. Both groups were similar with respect to their knowledge of advanced cardiovascular life support as measured by a pretest (P = 0.92).</AbstractText>We found those participants who were presented with electronic, physiologically triggered cognitive aids were more likely to appropriately treat heart block by initiating transcutaneous pacing. We believe that adoption of a high-functioning anesthesia information management system designed to detect physiologic perturbations and present appropriate decision support tools would lead to safer intraoperative care.</AbstractText>
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2,335,070 |
Comparison of the Effects of Benson Muscle Relaxation and Nature Sounds on the Fatigue in Patients With Heart Failure: A Randomized Controlled Clinical Trial.
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This study was conducted with the aim of comparing the effects of Benson muscle relaxation and nature sounds on fatigue in patients with heart failure. Fatigue and exercise intolerance as prevalent symptoms experienced by patients with heart failure can cause the loss of independence in the activities of daily living. It can also damage self-care and increase dependence to others, which subsequently can reduce the quality of life. This randomized controlled clinical trial was conducted in an urban area of Iran in 2016. Samples were consisted of 105 hospitalized patients with heart failure chosen using a convenience sampling method. They were assigned to relaxation, nature sounds, and control groups using a randomized block design. In addition to routine care, the Benson muscle relaxation and nature sounds groups received interventions in mornings and evenings twice a day for 20 minutes within 3 consecutive days. A 9-item questionnaire was used to collect data regarding fatigue before and after the interventions. Relaxation and nature sounds reduced fatigue in patients with heart failure in comparison to the control group. However, no statistically significant difference was observed between the interventions. Benson muscle relaxation and nature sounds are alternative methods for the reduction of fatigue in patients with heart failure. They are inexpensive and easy to be administered and upon patients' preferences can be used by nurses along with routine nursing interventions.
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2,335,071 |
Comparative Evaluation of Ropivacaine and Fentanyl Versus Ropivacaine and Fentanyl with Clonidine for Postoperative Epidural Analgesia in Total Knee Replacement Surgery.
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Clonidine an alpha 2 adrenoceptor agonist possesses analgesic properties and has been used as an adjuvant in epidural analgesia. The addition of clonidine to other analgesics may result in enhanced analgesia through additive mechanisms or synergistic mechanisms. The enhanced analgesia may lead to a decrease in the dosage of analgesic drugs along with reduction of side effects.</AbstractText>The purpose of this study was to evaluate the effect of adding clonidine to epidural ropivacaine and fentanyl mixture in terms of quality of analgesia and side effects in patients of total knee replacement surgery.</AbstractText>A prospective randomised double blind study was conducted on 60 patients of ASA physical status I, II and III who underwent unilateral total knee replacement surgery under combined spinal epidural anaesthesia. Patients were divided into two Groups A and B randomly. Postoperatively Group A received continuous epidural infusion of ropivacaine 2 mg.ml -1</sup> and fentanyl 2 μg.ml -1</sup> along with clonidine 2 μg.ml-1</sup> in the range of 3-7 ml.hr-1</sup> while Group B received the ropivacaine and fentanyl epidural solution. The postoperative VAS scores, haemodynamic parameters, motor block, sedation, nausea, vomiting and any other significant side effects were noted. The two groups were compared with student's t-test, Pearson's Chi square test and t-test using SPSS statistical software.</AbstractText>Visual analog scale scores were lower in Group A (3.38) than in Group B (3.72). The average infusion rate was lower in Group A (4.7 ± 0.7 ml.hr -1</sup>) than in Group B (5.5 ± 0.7 ml.hr-1</sup>). Patients in Group A required less dosage of rescue pain medication Paracetamol (1g i.v.), diastolic pressure and heart rate were lower in Group A. The groups were comparable in terms of sedation, motor block and nausea vomiting.</AbstractText>Clonidine added to a ropivacaine and fentanyl mixture augmented the postoperative epidural analgesia without significant side effects.</AbstractText>
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2,335,072 |
Preparation of viable adult ventricular myocardial slices from large and small mammals.
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This protocol describes the preparation of highly viable adult ventricular myocardial slices from the hearts of small and large mammals, including rodents, pigs, dogs and humans. Adult ventricular myocardial slices are 100- to 400-μm-thick slices of living myocardium that retain the native multicellularity, architecture and physiology of the heart. This protocol provides a list of the equipment and reagents required alongside a detailed description of the methodology for heart explantation, tissue preparation, slicing with a vibratome and handling of myocardial slices. Supplementary videos are included to visually demonstrate these steps. A number of critical steps are addressed that must be followed in order to prepare highly viable myocardial slices. These include identification of myocardial fiber direction and fiber alignment within the tissue block, careful temperature control, use of an excitation-contraction uncoupler, optimal vibratome settings and correct handling of myocardial slices. Many aspects of cardiac structure and function can be studied using myocardial slices in vitro. Typical results obtained with hearts from a small mammal (rat) and a large mammal (human) with heart failure are shown, demonstrating myocardial slice viability, maximum contractility, Ca<sup>2+</sup> handling and structure. This protocol can be completed in ∼4 h.
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2,335,073 |
Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease.
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Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively. The starting dose in both trials was three 1-g (elemental iron 210 mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in the phase 2 and 3 trials to lower serum phosphate concentrations to a target range (0.97-1.13 mmol/L) and to achieve a ≥10-g/L hemoglobin increase, respectively. Safety was assessed in all patients who received ≥1 dose of FC (n = 190) and placebo (n = 188). Treatment-emergent adverse events (AEs) were reported in 143 of 190 (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients; gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%], respectively). Specific events reported in >5% of patients (FC vs. placebo, respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39 [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18 [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest serum phosphate decline, with few excursions below the normal range. When used for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at higher rates than placebo, while simultaneously correcting two of the principal metabolic manifestations of CKD (iron deficiency anemia and relative hyperphosphatemia).
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2,335,074 |
Comparison of Two Methods: Spinal Anesthesia and Ischiorectal Block on Post Hemorrhoidectomy Pain and Hospital Stay: A Randomized Control Trial.
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Hemorrhoidectomy is one of the most common hemorrhoid surgery. Many areas are innervated by nerves, and this makes the surgery to be very painful. Various anesthetic methods have been proposed, and the number of investigations and procedures demonstrated the absence of a reliable method for reducing pain. This study compares the cavity ischiorectal block with spinal anesthesia in reducing postoperative pain, analgesic consumption, and hospital stay.</AbstractText>This study is a randomized control trial carried out on seventy patients sampled. Thirty-five (35) among them were placed in spinal anesthesia group, and the other 35 were placed in the ischiorectal block group. According to the study, questionnaire was designed in such a way that postoperative variables such as postoperative pain, analgesic consumption, changes in blood pressure, heart rate and hospital stay in both groups were evaluated and compared.</AbstractText>IRCT2015111616516N3 ( http://en.search.irct.ir/search?query=IRCT2015111616516N3 ) Results: In this study, the pain scores on Visual Analogue Scale (VAS) at 0, 6, 12, and 24 hr for spinal anesthesia group after surgery were 0, 3.08 ± 0.78, 2.05 ± 1.02, 1.11 ± 0.83, respectively (p < 0.05). That of ischiorectal blocks were 0.98 ± 0.25, 1.57 ± 0.81, 0.91 ± 0.91, and 0.63 ± 0.31 respectively, which indicated lesser pain after surgery in the ischiorectal block at 6, 12, and 24 hr. In this study, out of the 35 patients that underwent spinal anesthesia, 28 patients (80%) were hospitalized in the first 6 hr, 13 patients (37.1%) in the second 6 hr, 3 patients (8.6%) in the second 12 hr after surgery. For patients under the ischiorectal block, the number of patients hospitalized were 13 patients (37.1%), in the first 6 hr, 4 patients (11.4%) in the second 6 hr, and 1 (2.9%) were hospitalized in the second 12 hr after surgery (p < 0.05).</AbstractText>Ischiorectal blocks causes less pain, require fewer painkillers, and reduces the hospital stay after surgery than spinal anesthesia.</AbstractText>
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2,335,075 |
Ajmaline blocks I<sub>Na</sub> and I<sub>Kr</sub> without eliciting differences between Brugada syndrome patient and control human pluripotent stem cell-derived cardiac clusters.
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The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both I<sub>Na</sub> and I<sub>Kr</sub>. Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A sodium channel mutations), analysis of hiPSC-CMs from patients and controls revealed that differentiation and action potential parameters were similar. Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation-recovery interval consistently across all lines. We conclude that ajmaline can block both depolarisation and repolarisation of hiPSC-CMs at the cellular level, but that a more refined integrated tissue model may be necessary to elicit differences in its effect between BrS patients and controls.
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2,335,076 |
Structural basis for the antiarrhythmic blockade of a potassium channel with a small molecule.
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The acetylcholine-activated inward rectifier potassium current ( I<sub>KACh</sub>) is constitutively active in persistent atrial fibrillation (AF). We tested the hypothesis that the blocking of I<sub>KACh</sub> with the small molecule chloroquine terminates persistent AF. We used a sheep model of tachypacing-induced, persistent AF, molecular modeling, electrophysiology, and structural biology approaches. The 50% inhibition/inhibitory concentration of I<sub>KACh</sub> block with chloroquine, measured by patch clamp, was 1 μM. In optical mapping of sheep hearts with persistent AF, 1 μM chloroquine restored sinus rhythm. Molecular modeling suggested that chloroquine blocked the passage of a hydrated potassium ion through the intracellular domain of Kir3.1 (a molecular correlate of I<sub>KACh</sub>) by interacting with residues D260 and F255, in proximity to I228, Q227, and L299. <sup>1</sup>H <sup>15</sup>N heteronuclear single-quantum correlation of purified Kir3.1 intracellular domain confirmed the modeling results. F255, I228, Q227, and L299 underwent significant chemical-shift perturbations upon drug binding. We then crystallized and solved a 2.5 Å X-ray structure of Kir3.1 with F255A mutation. Modeling of chloroquine binding to the mutant channel suggested that the drug's binding to the pore becomes off centered, reducing its ability to block a hydrated potassium ion. Patch clamp validated the structural and modeling data, where the F255A and D260A mutations significantly reduced I<sub>KACh</sub> block by chloroquine. With the use of numerical and structural biology approaches, we elucidated the details of how a small molecule could block an ion channel and exert antiarrhythmic effects. Chloroquine binds the I<sub>KACh</sub> channel at a site formed by specific amino acids in the ion-permeation pathway, leading to decreased I<sub>KACh</sub> and the subsequent termination of AF.-Takemoto, Y., Slough, D. P., Meinke, G., Katnik, C., Graziano, Z. A., Chidipi, B., Reiser, M., Alhadidy, M. M., Ramirez, R., Salvador-Montañés, O., Ennis, S., Guerrero-Serna, G., Haburcak, M., Diehl, C., Cuevas, J., Jalife, J., Bohm, A., Lin,Y.-S., Noujaim, S. F. Structural basis for the antiarrhythmic blockade of a potassium channel with a small molecule.
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2,335,077 |
Parent Cardiac Response in the Context of Their Child's Completion of the Cold Pressor Task: A Pilot Study.
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Parents' ability to regulate their emotions is essential to providing supportive caregiving behaviours when their child is in pain. Extant research focuses on parent self-reported experience or observable behavioural responses. Physiological responding, such as heart rate (HR) and heart rate variability (HRV), is critical to the experience and regulation of emotions and provides a complementary perspective on parent experience; yet, it is scarcely assessed. This pilot study examined parent (<i>n</i> = 25) cardiac response (HR, HRV) at rest (neutral film clip), immediately before the cold pressor task (pre-CPT), and following the CPT (post-CPT). Further, variables that may influence changes in HR and HRV in the context of pediatric pain were investigated, including (1) initial HRV, and (2) parent perception of their child's typical response to needle procedures. Time-domain (root mean square of successive differences; RMSSD) and frequency-domain (high-frequency heart rate variability; HF-HRV) parameters of HRV were computed. HR and HF-HRV varied as a function of time block. Typical negative responses to needle pain related to higher parental HR and lower HRV at rest. Parents with higher HRV at baseline experienced the greatest decreases in HRV after the CPT. Consequently, considering previous experience with pain and resting HRV levels are relevant to understanding parent physiological responses before and after child pain.
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2,335,078 |
Virtual reality for stroke rehabilitation.
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Virtual reality and interactive video gaming have emerged as recent treatment approaches in stroke rehabilitation with commercial gaming consoles in particular, being rapidly adopted in clinical settings. This is an update of a Cochrane Review published first in 2011 and then again in 2015.</AbstractText>Primary objective: to determine the efficacy of virtual reality compared with an alternative intervention or no intervention on upper limb function and activity.Secondary objectives: to determine the efficacy of virtual reality compared with an alternative intervention or no intervention on: gait and balance, global motor function, cognitive function, activity limitation, participation restriction, quality of life, and adverse events.</AbstractText>We searched the Cochrane Stroke Group Trials Register (April 2017), CENTRAL, MEDLINE, Embase, and seven additional databases. We also searched trials registries and reference lists.</AbstractText>Randomised and quasi-randomised trials of virtual reality ("an advanced form of human-computer interface that allows the user to 'interact' with and become 'immersed' in a computer-generated environment in a naturalistic fashion") in adults after stroke. The primary outcome of interest was upper limb function and activity. Secondary outcomes included gait and balance and global motor function.</AbstractText>Two review authors independently selected trials based on pre-defined inclusion criteria, extracted data, and assessed risk of bias. A third review author moderated disagreements when required. The review authors contacted investigators to obtain missing information.</AbstractText>We included 72 trials that involved 2470 participants. This review includes 35 new studies in addition to the studies included in the previous version of this review. Study sample sizes were generally small and interventions varied in terms of both the goals of treatment and the virtual reality devices used. The risk of bias present in many studies was unclear due to poor reporting. Thus, while there are a large number of randomised controlled trials, the evidence remains mostly low quality when rated using the GRADE system. Control groups usually received no intervention or therapy based on a standard-care approach.</AbstractText>results were not statistically significant for upper limb function (standardised mean difference (SMD) 0.07, 95% confidence intervals (CI) -0.05 to 0.20, 22 studies, 1038 participants, low-quality evidence) when comparing virtual reality to conventional therapy. However, when virtual reality was used in addition to usual care (providing a higher dose of therapy for those in the intervention group) there was a statistically significant difference between groups (SMD 0.49, 0.21 to 0.77, 10 studies, 210 participants, low-quality evidence).</AbstractText>when compared to conventional therapy approaches there were no statistically significant effects for gait speed or balance. Results were statistically significant for the activities of daily living (ADL) outcome (SMD 0.25, 95% CI 0.06 to 0.43, 10 studies, 466 participants, moderate-quality evidence); however, we were unable to pool results for cognitive function, participation restriction, or quality of life. Twenty-three studies reported that they monitored for adverse events; across these studies there were few adverse events and those reported were relatively mild.</AbstractText><AbstractText Label="AUTHORS' CONCLUSIONS">We found evidence that the use of virtual reality and interactive video gaming was not more beneficial than conventional therapy approaches in improving upper limb function. Virtual reality may be beneficial in improving upper limb function and activities of daily living function when used as an adjunct to usual care (to increase overall therapy time). There was insufficient evidence to reach conclusions about the effect of virtual reality and interactive video gaming on gait speed, balance, participation, or quality of life. This review found that time since onset of stroke, severity of impairment, and the type of device (commercial or customised) were not strong influencers of outcome. There was a trend suggesting that higher dose (more than 15 hours of total intervention) was preferable as were customised virtual reality programs; however, these findings were not statistically significant.</AbstractText>
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2,335,079 |
N-Terminal B-type Natriuretic Peptide in Heart Failure.
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Plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a guideline-mandated biomarker in heart failure (HF). Used as an inclusion criterion for therapeutic trials, NT-proBNP enriches trial populations and is a valid surrogate endpoint. Its diagnostic performance is best validated in acute decompensated HF (ADHF). NT-proBNP offers prognostic information independent of standard clinical predictors and refines risk stratification. With the advent of combined angiotensin 2 type 1 receptor blockade and neprilysin inhibition (ARNI) NT-proBNP retains its relationship to cardiac status and is the marker of choice in assessment of possible ADHF and in serial monitoring of HF patients receiving ARNI treatment.
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2,335,080 |
Combination Analgesia for Neonatal Circumcision: A Randomized Controlled Trial.
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There is no consensus on the most effective pain management for neonatal circumcision. We sought to compare different modalities.</AbstractText>This is a double-blinded randomized controlled trial comparing 3 combination analgesics used during circumcision (EMLA + sucrose; EMLA + sucrose + dorsal penile nerve block [DPNB]; EMLA + sucrose + ring block [RB]) with the traditional topical analgesic cream EMLA alone. The trial was set in the normal nursery of a teaching hospital. The sample included 70 healthy male newborns, randomly assigned to intervention and control groups at a 2:1 ratio. Infants were videotaped (face and torso) during the procedure for assessment of pain by 2 blinded, independent reviewers. The primary outcome measure is the Neonatal Infant Pain Scale score. Secondary outcomes include heart rate, oxygen saturation, and crying time.</AbstractText>Neonatal Infant Pain Scale scores were significantly lower in the intervention groups (EMLA + sucrose, mean [SD]: 3.1 [1.33]; EMLA + sucrose + DPNB: 3 [1.33]; EMLA + sucrose + RB: 2.45 [1.27]) compared with the control (5.5 [0.53]). Between-group analyses showed RB + EMLA + sucrose to be significantly more effective than EMLA + sucrose; EMLA + sucrose + DPNB (P</i> = .009 and P</i> = .002, respectively). Interrater reliability was κ = 0.843. Significant increase in heart rate (139.27 [9.63] to 163 [13.23] beats per minute) and crying time (5.78 [6.4] to 45.37 [12.39] seconds) were noted in the EMLA group.</AbstractText>During neonatal circumcision in boys, the most effective analgesia is RB combined with oral sucrose and EMLA cream.</AbstractText>Copyright © 2017 by the American Academy of Pediatrics.</CopyrightInformation>
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2,335,081 |
[A concentration-response observation of hydromorphone combined with ropivacaine in labor analgesia].
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<b>Objective:</b> To investigate the median effective dose (ED(50)) of hydromorphone and the appropriate concentration of ropivacaine combined with hydromorphone in epidural labor analgesia. <b>Methods:</b> One hundred and forty nulliparous women undergoing labor selected for delivery with epidural analgesia were enrolled in our hospital from January to June 2016. The first of top 50 women received 0.12% ropivacaine plus 20 μg/ml hydromorphone complex solution, then sequential women were used the modified sequential method to determine the ED(50) and ED(95) of hydromorphone. The other 90 women were randomly divided and receieved 0.08% ropivacaine and 15 μg/ml hydromorphone(H1 group), 0.10% ropivacaine and 15 μg/ml hydromorphone (H2 group), 0.12% ropivacaine and 15 μg/ml hydromorphone (group H3) respectively for epidural labor analgesia. In the course of labor, block levels of epidural analgesia, the Bromage scores, analgesia scores and fetal heart rate-uterine concraction were monitored. In addition, onset time of anesthesia, labor time, mode of delivery, cases of increased oxytocin using, neonatal Apgar score, incidence of nausea and vomiting, itching and fetal heart reduction were recorded. <b>Results:</b> The ED(50) and ED(95) values of hydromorphone were 10.49 (95% <i>CI</i>: 8.89-11.79) and 15.15 (95% <i>CI</i>: 13.25-22.25) μg/ml respectively. The onset time in group H1 was significantly longer than those in group H2 and H3((14.23±3.82) , ( 11.32±2.16), (10.83±2.56)min, respectively), the difference was statistically significant (<i>t</i>=5.854, 6.212, all <i>P</i><0.05). Analgesic VAS score at 30, 60 and 90 min time points in H1 group was significantly higher than that in H2 group and H3 group (all <i>P</i><0.05). VAS score at withdrawal in H1 group was significantly higher than that in group H3 ( (3.25±0.75) vs (0.27±0.12) ), the difference was statistically significant ( <i>t</i>=9.314, <i>P</i><0.05). VAS scores at the fourth, fifth, sixth contractions after analgesia in H1 group were significantly higher than those in H2 and H3 groups (all <i>P</i><0.05). The incidence of motor nerve block in group H3 was higher than that in group H1 and group H2 (26.67%, 6.66%, 3.33%, respectively), the difference was statistically significant (χ(2)=6.413, 4.320, all <i>P</i><0.05). <b>Conclusions:</b> 0.10% ropivacaine combined with 15 μg/ml hydromorphone has a good analgesic effect, slight motor block, high safety and worthy clinical application for labor analgesia.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Y Y</ForeName><Initials>YY</Initials><AffiliationInfo><Affiliation>Department of Anesthesiology, Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>H</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Mao</LastName><ForeName>W L</ForeName><Initials>WL</Initials></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>R H</ForeName><Initials>RH</Initials></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>M J</ForeName><Initials>MJ</Initials></Author><Author ValidYN="Y"><LastName>Shao</LastName><ForeName>L X</ForeName><Initials>LX</Initials></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>M P</ForeName><Initials>MP</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>J</ForeName><Initials>J</Initials></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Zhonghua Yi Xue Za Zhi</MedlineTA><NlmUniqueID>7511141</NlmUniqueID><ISSNLinking>0376-2491</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000577">Amides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000701">Analgesics, Opioid</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical><Chemical><RegistryNumber>7IO5LYA57N</RegistryNumber><NameOfSubstance UI="D000077212">Ropivacaine</NameOfSubstance></Chemical><Chemical><RegistryNumber>Q812464R06</RegistryNumber><NameOfSubstance UI="D004091">Hydromorphone</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000577" MajorTopicYN="N">Amides</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015360" MajorTopicYN="Y">Analgesia, Epidural</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016362" MajorTopicYN="N">Analgesia, Obstetrical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000701" MajorTopicYN="N">Analgesics, Opioid</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D036861" MajorTopicYN="Y">Delivery, Obstetric</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004091" MajorTopicYN="N">Hydromorphone</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007743" MajorTopicYN="N">Labor, Obstetric</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000077212" MajorTopicYN="N">Ropivacaine</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="chi"><b>目的：</b> 探讨氢吗啡酮复合罗哌卡因行硬膜外分娩镇痛时氢吗啡酮的半数有效剂量(ED(50))和罗哌卡因的适宜有效浓度。 <b>方法：</b> 选择2016年1至6月接受分娩镇痛的初产妇140例，前50例患者中第1个患者接受0.12%罗哌卡因＋20 μg/ml氢吗啡酮复合液，随后的产妇运用改良序贯法确定氢吗啡酮的ED(50)、95%有效剂量(ED(95))。另90例患者按照随机数字表法平均分为H1组、H2组、H3组，分别给予0.08%罗哌卡因＋15 μg/ml氢吗啡酮(H1组)、0.10%罗哌卡因＋15 μg/ml氢吗啡酮(H2组)及0.12%罗哌卡因＋15 μg/ml氢吗啡酮(H3组)。监测分娩镇痛过程中阻滞平面和运动阻滞(Bromage评分)、镇痛评分及宫缩胎心；记录麻醉起效时间、产程时间、分娩方式、缩宫素使用增加例数及新生儿Apgar评分，记录恶心、呕吐、瘙痒、胎心减速等不良反应发生率。 <b>结果：</b> 氢吗啡酮的ED(50)值及ED(95)值分别为10.49 μg/ml(95% <i>CI</i>：8.89～11.79)和15.15 μg/ml(95% <i>CI</i>：13.25～22.25)。H1组起效时间为(14.23±3.82)min，明显长于H2组的(11.32±2.16)min及H3组的(10.83±2.56)min，差异有统计学意义 (<i>t</i>＝5.854、6.212，均<i>P</i><0.05)，H1组镇痛后30、60和90 min时的视觉模拟评分(VAS)明显高于H2、H3组(均<i>P</i><0.05)，H1组停药时的VAS评分为(3.25±0.75)分，明显高于H3组(0.27±0.12)分，差异有统计学意义(<i>t</i>＝9.314，<i>P</i><0.05)。H1组在镇痛后第4、5、6次宫缩时的VAS评分明显高于H2、H3组(均<i>P</i><0.05)。H3组运动神经阻滞发生率为26.67%，明显高于H1、H2组的6.66%、3.33%，差异有统计学意义(χ(2)＝6.413、4.320，均<i>P</i><0.05)。 <b>结论：</b> 0.10%罗哌卡因复合15 μg/ml氢吗啡酮行分娩镇痛时镇痛效果好、无运动阻滞、安全性高，值得临床推广。.
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2,335,082 |
Heart rate variability and plasma nephrines in the evaluation of heat acclimatisation status.
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Heat adaptation (HA) is critical to performance and health in a hot environment. Transition from short-term heat acclimatisation (STHA) to long-term heat acclimatisation (LTHA) is characterised by decreased autonomic disturbance and increased protection from thermal injury. A standard heat tolerance test (HTT) is recommended for validating exercise performance status, but any role in distinguishing STHA from LTHA is unreported. The aims of this study were to (1) define performance status by serial HTT during structured natural HA, (2) evaluate surrogate markers of autonomic activation, including heart rate variability (HRV), in relation to HA status.</AbstractText>Participants (n = 13) were assessed by HTT (60-min block-stepping, 50% VO2</sub>peak) during STHA (Day 2, 6 and 9) and LTHA (Day 23). Core temperature (Tc) and heart rate (HR) were measured every 5 min. Sampling for HRV indices (RMSSD, LF:HF) and sympathoadrenal blood measures (cortisol, nephrines) was undertaken before and after (POST) each HTT.</AbstractText>Significant (P < 0.05) interactions existed for Tc, logLF:HF, cortisol and nephrines (two-way ANOVA; HTT by Day). Relative to LTHA, POST results differed significantly for Tc (Day 2, 6 and 9), HR (Day 2), logRMSSD (Day 2 and Day 6), logLF:HF (Day 2 and Day 6), cortisol (Day 2) and nephrines (Day 2 and Day 9). POST differences in HRV (Day 6 vs. 23) were + 9.9% (logRMSSD) and - 18.6% (logLF:HF).</AbstractText>Early reductions in HR and cortisol characterised STHA, whereas LTHA showed diminished excitability by Tc, HRV and nephrine measures. Measurement of HRV may have potential to aid real-time assessment of readiness for activity in the heat.</AbstractText>
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2,335,083 |
The effect of nature sounds on physiological indicators among patients in the cardiac care unit.
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Environmental noises may create physiological and psychological disorders in patients hospitalized in the CCU. Therefore, this study was conducted to investigate the effects of nature sounds on physiological indicators among patients in the CCU.</AbstractText><AbstractText Label="MATERIALS & METHODS" NlmCategory="METHODS">This randomized clinical trial was conducted on 93 patients hospitalized in the cardiac care units of three teaching hospitals in 2016. The patients were selected using the convenient method with three randomized blocks. The patients were assigned into three groups as nature sounds, silence that received a set of headphones without playing sounds, and control groups. In addition to routine care, the patients in the intervention group listened to nature sounds for 30 min using a set of headphones for two days. The patients in the control group only received routine care. In addition to routine care, the patients in the silence group used a set of headphones for 30 min to block noises and no sound was played for them. Physiological indicators such as heartbeat rate, systolic and diastolic blood pressures, respiration rate, and arterial O2</sub> saturation were assessed using monitoring devices. Descriptive and inferential statistics were used for data analysis via the SPSS software.</AbstractText>Nature sounds and silence had no statistically significant effects on physiological indicators. However, a statistically significant difference was reported in the heart rate in the nature sound group before and after the intervention in the first day of the intervention (P = 0.046). In the second day of the intervention, there were statistically significant differences in the diastolic blood pressure in the nature sounds group (P = 0.028), heart rate (P = 0.001) and diastolic blood pressure (P = 0.013) in the silence group, and heart rate (P = 0.014) in the control group before and after the intervention.</AbstractText>Listening to nature sounds or the use of headphones blocked environmental noises and could influence mean arterial pressure. Future studies can examine the effects of this intervention implemented for a longer term using nature sounds by patients.</AbstractText>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,084 |
Self-Assembled Nanomicelles as MRI Blood-Pool Contrast Agent.
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Gadolinium-loaded nanomicelles show promise as future magnetic resonance imaging (MRI) contrast agents (CAs). Their increased size and high gadolinium (Gd) loading gives them an edge in proton relaxivity over smaller molecular Gd-complexes. Their size and stealth properties are fundamental for their long blood residence time, opening the possibility for use as blood-pool contrast agents. Using l-tyrosine as a three-functional scaffold we synthesized a nanostructure building block 8. The double C18 aliphatic chain on one side, Gd-1,4,7,10-tetraazacyclododecane-1-4-7-triacetic acid (Gd-DO3A) with access to bulk water in the center and 2 kDa PEG on the hydrophilic side gave the amphiphilic properties required for the core-shell nanomicellar architecture. The self-assembly into Gd-loaded monodispersed 10-20 nm nanomicelles occurred spontaneously in water. These nanomicelles (Tyr-MRI) display very high relaxivity at 29 mm<sup>-1</sup>  s<sup>-1</sup> at low field strength and low cytotoxicity. Good contrast enhancement of the blood vessels and the heart together with prolonged circulation time in vivo, makes Tyr-MRI an excellent candidate for a new supramolecular blood-pool MRI CA.
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2,335,085 |
Evaluation of intravenous regional anaesthesia and four-point nerve block efficacy in the distal hind limb of dairy cows.
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Intravenous regional anaesthesia (IVRA) and hindfoot four-point nerve block anaesthesia (NBA) are recommended for local anaesthesia (LA) in the distal limb of dairy cows. Two studies were conducted to compare the efficacy, time until onset and stress responses to IVRA and NBA in dairy cows. In the first cross-over designed study, eight healthy unsedated German Holstein cows, restrained in lateral recumbency (LR) on a surgical tipping table, were treated with IVRA and NBA using procaine 2% as a local anaesthetic. Distal limb desensitization was tested by electrical (e-), mechanical (m-) and thermal (t-) nociceptive stimulation 10 min before and 15 and 30 min after LA. Hormonal-metabolic (blood concentrations of cortisol, lactate, non-esterified fatty acids, and glucose) and cardio-respiratory (heart and respiratory rate, mean arterial blood pressure) stress responses to treatment were assessed at predetermined intervals. In the second study, six healthy, unsedated German Holstein cows in LR were treated (crossover design) with IVRA and NBA. Short-interval e-stimulation was measured by the time until complete distal limb desensitization.</AbstractText>In the first study, four of eight cows responded to e-stimulation 15 min after IVRA, while none of the cows treated with NBA responded until the safety cut-off level was reached. E-stimulation revealed complete desensitization of the distal limb 30 min after LA in all cows. Half of the cows did not respond to m- and t-stimulation before LA, so no further evaluation was performed. Stress reactions to IVRA and NBA treatment were similar, but differences may have been masked by stress response to LR restraint. In the second study, complete desensitization was achieved 12.5 min after NBA, while one of the six cows still responded to e-stimulation 20 min after IVRA.</AbstractText>Hindfoot nerve block anaesthesia and intravenous regional anaesthesia induced complete desensitization of the distal hind limb in dairy cows. However, the anaesthesia onset after NBA was significantly faster than that of IVRA, which may be clinically relevant in the field, particularly when distal limb anaesthesia is required for major claw surgeries under time constraints.</AbstractText>
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2,335,086 |
Effect of Low Dose Remifentanil on Postoperative Pain Relief and Heart Rate Variability in Post-Anaesthesia Care Unit.
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Several reports have shown the negligible adverse effects of low-dose remifentanil on the autonomic nervous system. We propose that the administration of low-dose remifentanil would be beneficial without adverse respiratory and hemodynamic effects. This study aimed to examine the effects of low-dose remifentanil on postoperative pain relief and heart rate variability (HRV) after surgery.</AbstractText>In total, 20 patients, who underwent breast cancer surgery, were analysed for HRV in the post-anaesthesia care unit (PACU). A sedative dose of remifentanil was continuously infused if patients experienced pain while in PACU. The remifentanil infusion dose was determined by achieving analgesia with no adverse effects on hemodynamics and/or respiration. Variables of low-frequency power, high-frequency power and low-frequency power/high-frequency power ratio were measured before and after the administration of remifentanil. Pain score was expressed as the numeric rating scale (NRS) from 0 to 10.</AbstractText>The mean dosage of remifentanil administered as a continuous infusion was 0.029±0.0042 μg kg-1</sup> min-1</sup>. After remifentanil administration, the value of the NRS decreased from 4.2±2.9 to 2.7±2.6. In addition, the value of high-frequency power increased from 35.6±14.3 to 49.4±3.0.</AbstractText>The continuous infusion of low-dose remifentanil may reduce post-operative pain scores and trigger the relative activation of the parasympathetic nervous system in post-surgical patients. This indicates that continuous infusion of low-dose remifentanil may be a useful option for postoperative pain relief in cases where postoperative pain control proves inadequate even with the application of regional block technique.</AbstractText>
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2,335,087 |
Placement Of Cardiac PacemaKEr Trial (POCKET) - rationale and design: a randomized controlled trial.
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A pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs) to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET). The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket.</AbstractText>In October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years) and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS) 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device).</AbstractText>POCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.</AbstractText>
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2,335,088 |
Tendon split lengthening technique for flexor hallucis longus tendon rupture.
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Flexor hallucis longus (FHL) tendon rupture is a challenging injury to lead with clawing of the great toe when the FHL tendon is repaired too tight. When the diagnosis is delayed, the tendon ends may not be opposable because of contracture or poor tendon tissue.</AbstractText>A technique to reconstruct FHL tendon rupture without a free tendon graft is described. A split tendon lengthening is performed at the midfoot around the knot of Henry. Ankle block anesthesia is used to allow the patient's active movement of the interphalangeal (IP) joint to determine the appropriate length of the reconstructed tendon for maintaining balance and preventing the tendon from being too tight or too loose. Between May 2012 and September 2015, five patients with a total rupture of the FHL tendon, having tendon defect distal to the knot of Henry, were treated with split tendon lengthening.</AbstractText>Four patients could actively plantarflex the great toe IP joint. One patient who was operated under spinal anesthesia could not actively plantarflex the great toe IP joint, but did not have extension deformity and did not want another procedure. The mean American Orthopedic Foot and Ankle Society (AOFAS) score at a mean follow-up of 44 months was 92 points (range, 80-100).</AbstractText>This technique is described to overcome the difficulty of reconstructing the FHL tendon with tendon defect. The tendon defect could be repaired after split tendon lengthening without a free tendon graft.</AbstractText>
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2,335,089 |
[Bayes' syndrome in cardiac surgery: prevalence of interatrial block in patients younger than 65 years undergoing cardiac surgery and association with postoperative atrial fibrillation].
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Interatrial block (IAB) is a well-known entity that is associated with an increased risk of atrial fibrillation (AF). This association is called Bayes' syndrome. The aim of our study was to define the prevalence of IAB among patients younger than 65 years undergoing cardiac surgery and determine whether there is an association between the presence of interatrial conduction delay and postoperative atrial fibrillation (POAF).</AbstractText>A total of 207 patients were enrolled. Partial IAB was defined as P-wave>120ms. Advanced IAB was defined as P-wave>120ms+biphasic morphology in the inferior leads. Ocurrence of POAF was assessed and a comparative analysis was conducted between patients that did and did not develop AF.</AbstractText>IAB prevalence was 78.3% (partial 66.2%, advanced 12.1%). POAF occurred in 28.5% of all patients, and was more frequent among patients with advanced IAB (44%) compared to 27.7% and 24.4% of POAF among patients with partial IAB and without IAB, respectively. Patients who developed POAF were significantly older, had significantly higher NTproBNP, higher prevalence of atrial enlargement and thyroid disease. After multivariate analysis, advanced IAB was found to be independently associated with POAF.</AbstractText>IAB is a frequent finding among patients undergoing cardiac surgery. According to our results, advanced IAB is independently associated with POAF in younger patients (<65 years) undergoing cardiac surgery.</AbstractText>Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.</CopyrightInformation>
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2,335,090 |
Long-term thermal manipulation in the late incubation period can inhibit breast muscle development by activating endoplasmic reticulum stress in duck (Anasplatyrhynchos domestica).
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Poultry embryos are easily affected by environmental changings during incubation, thereinto, the temperature modification is the most important one, but the mechanism of temperature effects on bird eggs is not clear. By using RNA-seq, we have previously found that endoplasmic reticulum stress (ERS) may involve in regulating embryonic muscle development of duck under the influence of temperature alteration. To further clarify the role of ERS in the effect, in the present study, we detected the impact of increasing the incubation temperature by 1℃ during embryonic days 10-27 (E10-27) on the development of duck embryos, and investigated the changes in mRNA and protein expression of ERS marker genes and muscle-related genes under the thermal manipulation (TM). The results of relative weight comparison showed that only the relative weight of breast muscle was steadily decreased by TM from E10 to the first day after hatching (W0). Meanwhile, the real-time PCR and western-blot analysis revealed that raising the incubation temperature stimulated the expression of ERS marker genes in breast muscle at E20. The mRNA expressions of muscle hypertrophy and atrophy-related genes were also detected, and were not changed regularly, however, the protein expressions of hypertrophy-related genes were all decreased at both E20 and W0, and the protein expression of atrophy-related genes were up-regulated at E20. The protein expression of muscle proliferation-related genes were also decreased at E20. Additionally, these results were the same as that in the ERS positive control groups. Taken together, these results indicated that long-term TM during late embryonic period could block the development of duck breast muscle by inhibiting muscle hypertrophy and proliferation, and promoting muscle atrophy at a post-transcriptional level via the activation of ERS.
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2,335,091 |
Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.
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On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms.</AbstractText>We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia-reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia-reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901.</AbstractText>In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32-0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68-0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning-afternoon variation in hypoxia-reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia-reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia-reperfusion injury modulator CDKN1a/p21.</AbstractText>Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery.</AbstractText>Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.</AbstractText>Copyright © 2018 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,092 |
RNA versatility, flexibility, and thermostability for practice in RNA nanotechnology and biomedical applications.
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In recent years, RNA has attracted widespread attention as a unique biomaterial with distinct biophysical properties for designing sophisticated architectures in the nanometer scale. RNA is much more versatile in structure and function with higher thermodynamic stability compared to its nucleic acid counterpart DNA. Larger RNA molecules can be viewed as a modular structure built from a combination of many 'Lego' building blocks connected via different linker sequences. By exploiting the diversity of RNA motifs and flexibility of structure, varieties of RNA architectures can be fabricated with precise control of shape, size, and stoichiometry. Many structural motifs have been discovered and characterized over the years and the crystal structures of many of these motifs are available for nanoparticle construction. For example, using the flexibility and versatility of RNA structure, RNA triangles, squares, pentagons, and hexagons can be constructed from phi29 pRNA three-way-junction (3WJ) building block. This review will focus on 2D RNA triangles, squares, and hexamers; 3D and 4D structures built from basic RNA building blocks; and their prospective applications in vivo as imaging or therapeutic agents via specific delivery and targeting. Methods for intracellular cloning and expression of RNA molecules and the in vivo assembly of RNA nanoparticles will also be reviewed. WIREs RNA 2018, 9:e1452. doi: 10.1002/wrna.1452 This article is categorized under: RNA Methods > RNA Nanotechnology RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
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2,335,093 |
Transient denervation of viable myocardium after myocardial infarction does not alter arrhythmia susceptibility.
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Cardiac sympathetic nerves stimulate heart rate and force of contraction. Myocardial infarction (MI) leads to the loss of sympathetic nerves within the heart, and clinical studies have indicated that sympathetic denervation is a risk factor for arrhythmias and cardiac arrest. Two distinct types of denervation have been identified in the mouse heart after MI caused by ischemia-reperfusion: transient denervation of peri-infarct myocardium and sustained denervation of the infarct. Sustained denervation is linked to increased arrhythmia risk, but it is not known whether acute nerve loss in peri-infarct myocardium also contributes to arrhythmia risk. Peri-infarct sympathetic denervation requires the p75 neurotrophin receptor (p75NTR), but removal of p75NTR alters the pattern of sympathetic innervation in the heart and increases spontaneous arrhythmias. Therefore, we targeted the p75NTR coreceptor sortilin and the p75NTR-induced protease tumor necrosis factor-α-converting enzyme/A disintegrin and metalloproteinase domain 17 (TACE/ADAM17) to selectively block peri-infarct denervation. Sympathetic nerve density was quantified using immunohistochemistry for tyrosine hydroxylase. Genetic deletion of sortilin had no effect on the timing or extent of axon degeneration, but inhibition of TACE/ADAM17 with the protease inhibitor marimastat prevented the loss of axons from viable myocardium. We then asked whether retention of nerves in peri-infarct myocardium had an impact on cardiac electrophysiology 3 days after MI using ex vivo optical mapping of transmembrane potential and intracellular Ca<sup>2+</sup>. Preventing acute denervation of viable myocardium after MI did not significantly alter cardiac electrophysiology or Ca<sup>2+</sup> handling, suggesting that transient denervation at this early time point has minimal impact on arrhythmia risk. NEW & NOTEWORTHY Sympathetic denervation after myocardial infarction is a risk factor for arrhythmias. We asked whether transient loss of nerves in viable myocardium contributed to arrhythmia risk. We found that targeting protease activity could prevent acute peri-infarct denervation but that it did not significantly alter cardiac electrophysiology or Ca<sup>2+</sup> handling 3 days after myocardial infarction.
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2,335,094 |
Ion Channel Trafficking: Control of Ion Channel Density as a Target for Arrhythmias?
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The shape of the cardiac action potential (AP) is determined by the contributions of numerous ion channels. Any dysfunction in the proper function or expression of these ion channels can result in a change in effective refractory period (ERP) and lead to arrhythmia. The processes underlying the correct targeting of ion channels to the plasma membrane are complex, and have not been fully characterized in cardiac myocytes. Emerging evidence highlights ion channel trafficking as a potential causative factor in certain acquired and inherited arrhythmias, and therapies which target trafficking as opposed to pore block are starting to receive attention. In this review we present the current evidence for the mechanisms which underlie precise control of cardiac ion channel trafficking and targeting.
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2,335,095 |
LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8<sup>+</sup> T Cells after Heterologous Prime-Boost Vaccination against <i>Trypanosoma cruzi</i> Infection.
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Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as <i>Trypanosoma cruzi</i>, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8<sup>+</sup> T cells generated by heterologous prime-boost immunization during experimental infection with <i>T. cruzi</i>. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules. After anti-LFA-1, but not anti-VLA-4 treatment, all vaccinated mice displayed increased blood and tissue parasitemia, and quickly succumbed to infection. In addition, there was an accumulation of specific CD8<sup>+</sup> T cells in the spleen and lymph nodes and a decrease in the number of those cells, especially in the heart, suggesting that LFA-1 is important for the output of specific CD8<sup>+</sup> T cells from secondary lymphoid organs into infected organs such as the heart. The treatment did not alter CD8<sup>+</sup> T cell effector functions such as the production of pro-inflammatory cytokines and granzyme B, and maintained the proliferative capacity after treatment. However, the specific CD8<sup>+</sup> T cell direct cytotoxicity was impaired after LFA-1 blockade. Also, these cells expressed higher levels of Fas/CD95 on the surface, suggesting that they are susceptible to programmed cell death by the extrinsic pathway. We conclude that LFA-1 plays an important role in the migration of specific CD8<sup>+</sup> T cells and in the direct cytotoxicity of these cells.
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2,335,096 |
No. 350-Hirsutism: Evaluation and Treatment.
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To review the etiology, evaluation, and treatment of hirsutism.</AbstractText>A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment.</AbstractText>Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response.</AbstractText>At least 6 to 9 months of therapy are required to produce improvement in hirsutism.</AbstractText>The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination.</AbstractText>Hirsutism can be slowly but dramatically improved with a 3-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes, including weight loss and exercise, will lower serum androgen levels and improve self-esteem in patients with polycystic ovary syndrome. The patient should be educated regarding the associated health problems or long-term medical consequences of hyperandrogenism, particularly in the context of polycystic ovary syndrome, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease.</AbstractText>RECOMMENDATIONS.</AbstractText>Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,335,097 |
Laryngocardiac Reflex: A Case Report and Review of the Literature.
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The vagus nerve has sensory and motor function in the larynx, as well as parasympathetic function in the thorax and abdomen. Stimulation of the superior laryngeal nerve can cause reflexive bradycardia.</AbstractText>We describe a case of a 45-year-old man with pre-syncopal symptoms while exercising, and bradycardia found during cardiology workup. Radiography and flexible laryngoscopy showed evidence of a right-sided, vascular laryngeal mass. Exercise testing before and after superior laryngeal nerve block showed reversal of the symptoms with the block. Subsequent resection of the lymphovascular malformation with CO2</sub> laser eliminated the patient's symptoms.</AbstractText>This is the first case reported of the laryngocardiac reflex producing symptomatic bradycardia as a result of exercise-induced engorgement of a supraglottic lymphovascular malformation, which was then cured by surgical excision. We discuss this case and the literature regarding lymphovascular malformations in the airway and the neural pathways of the laryngocardiac reflex.</AbstractText>Published by Elsevier Inc.</CopyrightInformation>
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2,335,098 |
Association of built environment characteristics with adiposity and glycaemic measures.
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This study examined the cross-sectional and longitudinal relationships of built environment characteristics with adiposity and glycaemic measures.</AbstractText>Longitudinal study sample consisted of 4,010 Framingham Heart Study Offspring (baseline: 1998-2001; follow-up: 2005-2008) and Generation Three (baseline: 2002-2005; follow-up: 2008-2011) participants (54.8% women, baseline mean age 48.6 years). Built environment characteristics (intersection density, greenspace, recreation land and food stores) at baseline were collected. Adiposity and glycaemic measures (body mass index [BMI], waist circumference, abdominal subcutaneous and visceral adipose tissue, and fasting plasma glucose) at baseline and changes during 6.4-year follow-up were measured.</AbstractText>In cross-sectional models, higher intersection density and food store density (total food stores, fast food restaurants and supermarkets) were linearly associated with higher BMI (all p</i> < 0.05). Higher greenspace was associated with lower BMI, waist circumference, fasting plasma glucose, prevalent obesity and prevalent diabetes (all p</i> < 0.05). Longitudinally, higher intersection density and food store density, and lower greenspace were associated with smaller increases in abdominal visceral adipose tissue (all p</i> < 0.05). Higher densities of intersections, fast food restaurants and supermarkets were associated with smaller increases in fasting plasma glucose (all p</i> < 0.05).</AbstractText>Collectively, built environment characteristics are associated with adiposity and glycaemic traits, suggesting the potential mechanisms by which built environment influences cardiometabolic health.</AbstractText>
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2,335,099 |
Influence of exercise on the structure of the anterior chamber of the eye.
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To measure changes in anterior chamber structure before and after exercise in healthy individuals using anterior segment optical coherence tomography (ASOCT).</AbstractText>Thirty-two healthy young individuals performed jogging for 20 min. Eye blinking rate was recorded during rest and exercise. The anterior chamber angle (ACA), angle opening distance at 500 μm from the scleral spur (AOD500), trabecular-iris space area at 500 μm from the scleral spur (TISA500), iris concavity (IC), iris concavity ratio (CR), iris thickness at 750 μm from the scleral spur (IT750), anterior chamber depth (ACD), anterior chamber width (ACW), pupil diameter (PD), intraocular pressure (IOP), blood pressure (BP) and heart rate (HR) were recorded before and after exercise. Anterior chamber angle (ACA), AOD500, TISA500, IC, IT750, ACD, ACW and PD were measured with ASOCT.</AbstractText>Compared with rest, the blinking rate during exercise did not change significantly (13.04 ± 5.80 versus 13.52 ± 5.87 blinks/min, p = 0.645). The average IOP (15.4 ± 2.4 versus 12.4 ± 2.1 mmHg), ACA (35.96 ± 11.35 versus 40.25 ± 12.64 degrees), AOD500 (0.800 ± 0.348 versus 0.942 ± 0.387 mm), TISA500 (0.308 ± 0.155 versus 0.374 ± 0.193 mm2</sup> ), IC (-0.078 ± 0.148 versus -0.153 ± 0.159 mm) and CR (-0.027 ± 0.050 versus -0.054 ± 0.056) changed significantly (all p < 0.001), while the average IT750 (0.463 ± 0.084 versus 0.465 ± 0.086 mm; p = 0.492), ACD (3.171 ± 0.229 versus 3.175 ± 0.238 mm; p = 0.543) and ACW (11.768 ± 0.377 versus 11.755 ± 0.378 mm; p = 0.122) showed no significant change after exercise.</AbstractText>The blinking rate did not change significantly during exercise, while ACA, AOD500 and TISA500 increased after exercise. Exercise also induced or increased IC. These changes in anterior chamber structure were only associated with exercise, but not with the postexercise change in PD or IOP.</AbstractText>© 2017 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.</CopyrightInformation>
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