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2,335,200 |
Dosimetric evaluation of synthetic CT for magnetic resonance-only based radiotherapy planning of lung cancer.
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Interest in MR-only treatment planning for radiation therapy is growing rapidly with the emergence of integrated MRI/linear accelerator technology. The purpose of this study was to evaluate the feasibility of using synthetic CT images generated from conventional Dixon-based MRI scans for radiation treatment planning of lung cancer.</AbstractText>Eleven patients who underwent whole-body PET/MR imaging following a PET/CT exam were randomly selected from an ongoing prospective IRB-approved study. Attenuation maps derived from the Dixon MR Images and atlas-based method was used to create CT data (synCT). Treatment planning for radiation treatment of lung cancer was optimized on the synCT and subsequently copied to the registered CT (planCT) for dose calculation. Planning target volumes (PTVs) with three sizes and four different locations in the lung were planned for irradiation. The dose-volume metrics comparison and 3D gamma analysis were performed to assess agreement between the synCT and CT calculated dose distributions.</AbstractText>Mean differences between PTV doses on synCT and CT across all the plans were -0.1% ± 0.4%, 0.1% ± 0.5%, and 0.4% ± 0.5% for D95, D98 and D100, respectively. Difference in dose between the two datasets for organs at risk (OARs) had average differences of -0.14 ± 0.07 Gy, 0.0% ± 0.1%, and -0.1% ± 0.2% for maximum spinal cord, lung V20, and heart V40 respectively. In patient groups based on tumor size and location, no significant differences were observed in the PTV and OARs dose-volume metrics (p > 0.05), except for the maximum spinal-cord dose when the target volumes were located at the lung apex (p = 0.001). Gamma analysis revealed a pass rate of 99.3% ± 1.1% for 2%/2 mm (dose difference/distance to agreement) acceptance criteria in every plan.</AbstractText>The synCT generated from Dixon-based MRI allows for dose calculation of comparable accuracy to the standard CT for lung cancer treatment planning. The dosimetric agreement between synCT and CT calculated doses warrants further development of a MR-only workflow for radiotherapy of lung cancer.</AbstractText>
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2,335,201 |
Optical coherence tomography is a kid on the block: I would choose intravascular ultrasound.
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Intravascular imaging has improved our understanding of in vivo pathophysiology of coronary artery disease (CAD) and predicted decision-making in percutaneous coronary intervention (PCI). Intravascular ultrasound (IVUS) has emerged as the first clinical imaging method contributing significantly to modern PCI techniques. This modality has outlived many other intravascular techniques 26 years after its inception. It has assisted us in understanding dynamics of atherosclerosis and provides several unique insights into plaque burden, remodeling, and restenosis. It is useful as an imaging endpoint in large progression-regression trial and as workhorse in many catheterization laboratories. IVUS guidance appears to be most beneficial in complex lesion subsets that are being treated with drug-eluting stents. The recent introduction of optical coherence tomography (OCT), a light based imaging technique, has further expanded this field because of its higher resolution and faster image acquisition. The omnipresence of OCT raises the question: Does IVUS have a role in the era of OCT? Whether OCT is superior to IVUS in routine clinical practice? Even if OCT is currently gaining clinical significance in detailed planning of interventional strategies and stent optimization in complex lesion subsets, it is the much younger technique and has to prove its worth. Nevertheless, undoubtedly IVUS plays significant role in studies on coronary atherosclerosis and for guidance of PCI. In fact, both the methods are complementary rather than competitive.
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2,335,202 |
Changes in the food environment over time: examining 40 years of data in the Framingham Heart Study.
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Research has explored associations between diet, body weight, and the food environment; however, few studies have examined historical trends in food environments.</AbstractText>In the Framingham Heart Study Offspring (N = 3321) and Omni (N = 447) cohorts, we created food environment metrics in four Massachusetts towns utilizing geocoded residential, workplace, and food establishment addresses from 1971 to 2008. We created multilevel models adjusted for age, sex, education, and census tract poverty to examine trends in home, workplace, and commuting food environments.</AbstractText>Proximity to and density of supermarkets, fast-food, full service restaurants, convenience stores, and bakeries increased over time for residential, workplace, and commuting environments; exposure to grocery stores decreased. The greatest increase in access was for supermarkets, with residential distance to the closest supermarket 1406 m closer (95% CI 1303 m, 1508 m) by 2005-2008 than in 1971-1975. Although poorer census tracts had higher access to fast-food restaurants consistently across follow-up, this disparity dissipated over time, due to larger increases in proximity to fast-food in wealthier neighborhoods.</AbstractText>Access to most food establishment types increased over time, with similar trends across home, workplace, and commuter environments.</AbstractText>
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2,335,203 |
Approach to thyroid carcinoma in pregnancy.
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Thyroid carcinoma is the first cancer found in general population and the second diagnosed during pregnancy following the breast one. Diagnostic and therapeutic approaches to thyroid malignancy in pregnant women pose several and serious issues to the physicians. Even if there is no consensus about the surgical treatment of thyroid carcinomas during pregnancy, a large number of women undergo surgery over the world. The best surgical and anesthesiological treatment should be chosen after reaching a consensus between surgeons, anesthesiologists, obstetrics, and the patients. From 2000 to 2016, 18 pregnant patients underwent thyroidectomy under local anesthesia (cervical plexus block) combined with conscious sedation using benzodiazepines and opiates with ultrashort duration of action. Our 15-year experience on the thyroidectomies performed using the cervical plexus block combined with conscious sedation confirms that this combined technique offers a safe chance to defeat cancer also during pregnancy. Application of hypnosis could be an interesting alternative approach to pharmacological sedation in patients who would avoid intravenous drugs.
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2,335,204 |
An Effective Treatment for Heart Failure Caused by Valvular Heart Diseases: Thoracic Sympathetic Block.
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The pilot study is designed to investigate the effect of continuous thoracic sympathetic block (TSB) on cardiac function, reconstruction, and hemodynamic parameters in patients with heart failure resulting from valvular heart disease.</AbstractText>The cardiac function parameters, including left ventricle ejection fraction (LVEF), left ventricle end-diastole diameter (LVEDD), fractional shortening (FS), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), were measured in 19 patients before and after TSB treatment. The patients were also classified on the basis of NYHA classification system.</AbstractText>4 weeks of TSB administration improved cardiac function in 18 of 19 patients (94.74%). The patients' LVEF, LVEDD, and NT-proBNP were all improved significantly after treatment.</AbstractText>The favorable clinical outcome of TSB administration suggests an alternative treatment for the patients with heart failure caused by valvular dysfunctions.</AbstractText>
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2,335,205 |
Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.
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Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.
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2,335,206 |
Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective.
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To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective.</AbstractText>The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC. Response rates, event-free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER. EFS and OS were estimated by fitting parametric survival distributions to failure-time data from TOWER. Utility values were based on EORTC-8D derived from EORTC QLQ-C30 assessments in TOWER. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% per year.</AbstractText>The B-GEM projected blinatumomab to yield 1.92 additional life years and 1.64 additional quality-adjusted life years (QALYs) compared with SOC at an incremental cost of $180,642. The ICER for blinatumomab vs SOC was estimated to be $110,108/QALY gained in the base case. Cost-effectiveness was sensitive to the number and cost of inpatient days for administration of blinatumomab and SOC, and was more favorable in the sub-group of patients who had received no prior salvage therapy. At an ICER threshold of $150,000/QALY gained, the probability that blinatumomab is cost-effective was estimated to be 74%.</AbstractText>The study does not explicitly consider the impact of adverse events of the treatment; no adjustments for long-term transplant rates were made.</AbstractText>Compared with SOC, blinatumomab is a cost-effective treatment option for adults with R/R Ph - B-precursor ALL from the US healthcare perspective at an ICER threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its incremental survival and health-related quality-of-life (HRQoL) benefit over SOC.</AbstractText>
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2,335,207 |
Maternal autoimmune disorders and fetal defects.
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Maternal autoantibodies can cross the placenta and cause fetal damage. This article summarizes the development and management of fetal thyroid goiter in response to maternal Graves' disease and/or its treatment with antithyroid medication, fetal heart block due to maternal anti-Ro and anti-La antibodies, fetal athrogryposis multiplex congenita in association with maternal myasthenia gravis and fetal brain hemorrhage due to maternal autoimmune thrombocytopenia.
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2,335,208 |
Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.
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The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical <i>S</i>-adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes reflected fibrosis. These data support the novel finding that cardiac injury in CHB may occur secondary to abnormal remodeling due in part to upregulation of type 1 IFN response genes.<b>NEW & NOTEWORTHY</b> Congenital heart block is a rare disease of the fetal heart associated with maternal anti-Ro autoantibodies which can result in death and for survivors, lifelong pacing. This study provides in vivo and in vitro transcriptome-support that injury may be mediated by an effect of Type I Interferon on fetal fibroblasts.
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2,335,209 |
Analgesic and physiological effect of electroacupuncture combined with epidural lidocaine in goats.
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To investigate physiological and antinociceptive effects of electroacupuncture (EA) with lidocaine epidural nerve block in goats.</AbstractText>Prospective experimental trial.</AbstractText>Forty-eight hybrid male goats weighing 27 ± 2 kg.</AbstractText>The goats were randomly assigned to six groups: L2.2, epidural lidocaine (2.2 mg kg-1</sup>); L4.4, epidural lidocaine (4.4 mg kg-1</sup>); EA; EA-L1.1, EA with epidural lidocaine (1.1 mg kg-1</sup>); EA-L2.2, EA with epidural lidocaine (2.2 mg kg-1</sup>); and EA-L4.4, EA with epidural lidocaine (4.4 mg kg-1</sup>). EA was administered for 120 minutes. Epidural lidocaine was administered 25 minutes after EA started. Nociceptive thresholds of flank and thigh regions, abdominal muscle tone, mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR</sub>) and rectal temperature were recorded at 30, 60, 90, 120, 150 and 180 minutes.</AbstractText>Lidocaine dose-dependently increased nociceptive thresholds. There were no differences in nociceptive thresholds between L4.4 and EA from 30 to 120 minutes. The threshold in EA-L2.2 was lower than in EA-L4.4 from 30 to 120 minutes, but higher than in EA-L1.1 from 30 to 150 minutes or in L4.4 from 30 to 180 minutes. The abdominal muscle tone in EA-L2.2 was higher at 30 minutes, but lower at 90 and 120 minutes than at 0 minutes. There were no differences in muscle tone between L4.4 and L2.2 or EA-L4.4, and between any two of the three EA-lidocaine groups from 0 to 180 minutes. The fR</sub> and HR decreased in L4.4 at 60 and 90 minutes compared with 0 minutes. No differences in fR</sub>, HR, MAP and temperature among the groups occurred from 30 to 180 minutes.</AbstractText>EA combined with 2.2 mg kg-1</sup> epidural lidocaine provides better antinociceptive effect than 4.4 mg kg-1</sup> epidural lidocaine alone in goats. EA provided antinociception and allowed a decrease in epidural lidocaine dose.</AbstractText>Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,335,210 |
Regulation of Angiopoietin Signalling by Soluble Tie2 Ectodomain and Engineered Ligand Trap.
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Angiopoietin-1 (Angpt1) is a glycoprotein ligand important for maintaining the vascular system. It signals via a receptor tyrosine kinase expressed on the surface on endothelial cells, Tie2. This receptor can undergo regulated ectodomain cleavage that releases the ligand-binding domain (sTie2) into the circulation. The concentration of sTie2 is increased in a range of conditions, including peripheral arterial disease and myocardial infarction, where it has been suggested to bind and block Angpt1 resulting in vascular dysfunction. Here we use a joint mathematical modelling and experimental approach to assess the potential impact of sTie2 on the ability of Angpt1 to signal. We find that the concentrations of sTie2 relative to Angpt1 required to suppress signalling by the ligand are more than ten-fold higher than those ever seen in normal or disease conditions. In contrast to the endogenous sTie2, an engineered form of sTie2, which presents dimeric ligand binding sites, inhibits Angpt1 signalling at seventy-fold lower concentrations. While loss of Tie2 ectodomain can suppress Angpt1 signalling locally in the cells in which the receptor is lost, our study shows that the resulting increase in circulating sTie2 is unlikely to affect Angpt1 activity elsewhere in the body.
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2,335,211 |
The Importance of Right Ventricular Lead Positioning in Determining Outcomes of Cardiac Resynchronization Therapy.
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Cardiac resynchronization therapy is known to improve clinical outcomes in patients with heart failure and left ventricular dyssynchrony. However, the optimal positioning of the right ventricular lead is unknown, and there is conflicting data on the acute hemodynamic effects and long-term outcomes. Here, we present a case of a patient who underwent implantation of a dual-chamber pacemaker for complete heart block, but who after three months, still had symptoms consistent with New York Heart Association (NYHA) Class IV heart failure. After optimal medical therapy failed and a left ventricular lead was placed, he still remained symptomatic, so the right ventricular lead was repositioned from the right ventricular outflow tract to the right ventricular apex. Afterwards, the patient's symptoms improved from NYHA Class IV to NYHA Class II, and his left ventricular ejection fraction improved from 20% to 45%.
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2,335,212 |
Health-related quality of life and health preference of Chinese patients with diabetes mellitus managed in primary care and secondary care setting: decrements associated with individual complication and number of complications.
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Health-related quality of life (HRQoL) and health preference of patients with diabetes mellitus (DM) are essential in health economic evaluations but data on Chinese population is rare. This study aims to evaluate HRQoL and health preference of diabetic patients with different diabetic complications in Chinese population.</AbstractText>A cross-sectional study was conducted in 1275 patients with DM, including 518 subjects with various DM-related complications. HRQoL and health preference were estimated using SF-12 and SF-6D questionnaires, respectively. Disease status of DM and complications were identified from documented clinical diagnosis. Multivariable regression was used to investigate the effects of specific complications on HRQoL and health preference, adjusting for socio-demographic and clinical parameters.</AbstractText>The presence of any diabetic complication was associated with lower physical component summary (-3.81 points, P < 0.01), and end-stage renal disease (ESRD) showed greatest reduction (-7.05 points, P < 0.01). Mental component summary and mental health (MH) scores were not decreased in any of the diabetic complications. The health preference score for diabetic subjects without complications was 0.882 (95% CI, 0.778 to 0.989). The reductions of health preference score were significant for stroke (-0.042, 95% CI -0.072 to -0.012), ESRD (-0.055, 95% CI -0.093 to -0.017), and sight-threatening diabetic retinopathy (STDR) (-0.043, 95% CI -0.075 to -0.010), while heart disease had an insignificant reduction (-0.017, 95% CI -0.042 to 0.008).</AbstractText>The presence of any of the four major diabetic complications (heart disease, stroke, ESRD and STDR) was associated with lower HRQoL and health preference scores. Findings of this study facilitated the cost-effectiveness studies of alternative management strategies for prevention of diabetic complications in Chinese population.</AbstractText>
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2,335,213 |
Perfect storm: Therapeutic plasma exchange for a patient with thyroid storm.
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Thyroid storm is a potentially lethal complication of hyperthyroidism with increased thyroid hormones and exaggerated symptoms of thyrotoxicosis. First-line therapy includes methimazole (MMI) or propylthiouracil (PTU) to block production of thyroid hormones as a bridge toward definitive surgical treatment. Untreated thyroid storm has a mortality rate of up to 30%; this is particularly alarming when patients cannot tolerate or fail pharmacotherapy, especially if they cannot undergo thyroidectomy. Therapeutic plasma exchange (TPE) is an ASFA category III indication for thyroid storm, meaning the optimum role of this therapy is not established, and there are a limited number of cases in the literature. Yet TPE can remove T3 and T4 bound to albumin, autoantibodies, catecholamines and cytokines and is likely beneficial for these patients. We report a patient with thyroid storm who could not tolerate PTU, subsequently failed therapy with MMI, and was not appropriate for thyroidectomy. TPE was therefore performed daily for 4 days (1.0 plasma volume with 5% albumin replacement and 2 U of plasma). Over the treatment course, the patient's thyroid hormones normalized and symptoms of thyroid storm largely resolved; his T3 decreased from 2.27 to 0.81 ng/mL (normal 0.8-2.0), T4 decreased from 4.8 to 1.7 ng/mL (0.8-1.8), heart rate normalized, altered mental status improved, and he converted to normal sinus rhythm. He was ultimately discharged in euthyroid state. He experienced no side effects from his TPE procedures. TPE is a safe and effective treatment for thyroid storm when conventional treatments are not successful or appropriate.
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2,335,214 |
Femoral nerve block with propofol sedation versus general anesthesia in patients with severe cardiac dysfunction undergoing autologous myoblast sheet transplantation.
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Regional anesthesia is more favorable than general anesthesia in patients with severe comorbidity; however, data on the superiority of peripheral nerve blocks over general anesthesia in patients with severe cardiac dysfunction are lacking. We aimed to demonstrate that peripheral nerve blocks reduce perioperative analgesic requirements and promote faster recovery compared to general anesthesia.</AbstractText>We retrospectively evaluated intraoperative blood pressure, perioperative medications, and postoperative recovery in patients who underwent skeletal muscle harvesting for autologous myoblast sheet transplantation. We compared patients who received general anesthesia (group G, n = 27) to those who received femoral nerve block with propofol sedation (group B, n = 22).</AbstractText>Left ventricular ejection fraction was 24% on average, with no significant difference between groups. Compared with group G, a lower dose of propofol was used intraoperatively (1.25 versus 2.0 µg/mL, respectively; P < 0.001) and fewer patients required opioids (13.6 versus 100%, P < 0.01) in group B. Additionally, the lowest intraoperative mean blood pressure was higher (54 versus 48 mmHg, respectively; P = 0.02) in group B. More patients received postoperative analgesic drugs (51.9 versus 13.6%, P = 0.01) and they received them more frequently (1 [0-3] versus 0 [0-1], P = 0.02) in group G. The length of heart care unit stay was shorter in group B than group G (0 [0-18.5] versus 17 [0-47] h, respectively; P < 0.0001).</AbstractText>Femoral nerve block with sedation was more beneficial than general anesthesia in patients with severe cardiac dysfunction who underwent skeletal muscle harvesting for autologous myoblast sheet transplantation.</AbstractText>
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2,335,215 |
[Changes in electrocardiographic parameters in children with complete left bundle branch block early after transcatheter closure of ventricular septal defect].<Pagination><StartPage>663</StartPage><EndPage>667</EndPage><MedlinePgn>663-667</MedlinePgn></Pagination><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To observe the changes in electrocardiographic parameters in children with complete left bundle branch block (CLBBB) after the transcatheter closure of simple ventricular septal defect (VSD).</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">A total of 21 children with CLBBB early after transcatheter closure of perimembranous VSD were recruited. Another 21 children without any type of arrhythmia after transcatheter closure of perimembranous VSD were enrolled as the control group. The sex, age, and the size of occluder were matched between the two groups. The changes in the following indices were compared between the two groups: left ventricular voltage, QT interval, corrected QT interval (QTc), QT dispersion (QTd), corrected QT dispersion (QTcd), JT dispersion (JTd), and corrected JT dispersion (JTcd) on the electrocardiogram before transcatheter closure and at 1, 3, 5, 30 days after transcatheter closure.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Left ventricular voltage and JTcd changed with operation time in the CLBBB and control groups (P<0.05). There were interaction effects between time and grouping in the changes in left ventricular voltage and QTd (P<0.05). There was a significant difference in JTcd between the CLBBB and control groups (P<0.05). There was also a significant difference in left ventricular voltage between the CLBBB and control groups at 3 and 5 days after the transcatheter closure (P<0.05).</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">There are significant differences in electrocardiographic left ventricular voltage and JTcd between VSD children with and without CLBBB early after transcatheter closure. JTcd might be useful in predicting the development of CLBBB early after transcatheter closure of VSD.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, West China Second University Hospital/Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu 610041, China. [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Yong-Yi</ForeName><Initials>YY</Initials></Author><Author ValidYN="Y"><LastName>Hua</LastName><ForeName>Yi-Min</ForeName><Initials>YM</Initials></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Kai-Yu</ForeName><Initials>KY</Initials></Author><Author ValidYN="Y"><LastName>Ye</LastName><ForeName>Qiang-Hua</ForeName><Initials>QH</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Chuan</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Xiao</ForeName><Initials>X</Initials></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Song</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Ju-Fang</ForeName><Initials>JF</Initials></Author></AuthorList><Language>chi</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>Zhongguo Dang Dai Er Ke Za Zhi</MedlineTA><NlmUniqueID>100909956</NlmUniqueID><ISSNLinking>1008-8830</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002037" MajorTopicYN="N">Bundle-Branch Block</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006328" MajorTopicYN="Y">Cardiac Catheterization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="Y">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006345" MajorTopicYN="N">Heart Septal Defects, Ventricular</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011183" MajorTopicYN="N">Postoperative Complications</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="chi"><AbstractText Label="目的">观察单纯室间隔缺损（VSD）患儿介入封堵术后早期发生完全性左束支传导阻滞（CLBBB）患儿的心电图变化。</AbstractText><AbstractText Label="方法">纳入21例行膜周部VSD介入封堵且术后早期出现CLBBB的患儿，同时以性别、年龄及封堵器大小进行1：1配对，纳入同时期术后未合并任何心律失常的单纯膜周部VSD的患儿21例作为对照组。比较两组患儿组间及组内术前、术后1 d、术后3 d、术后5 d、术后30 d心电图左室电压、QT间期、心率校正的QT间期（QTc）、QT离散度（QTd）、心率校正的QT离散度（QTcd）、JT离散度（JTd）和心率校正的JT离散度（JTcd）的变化。</AbstractText><AbstractText Label="结果">两组患儿左室电压、JTcd随手术时间的变化而变化（<i>P</i> < 0.05）；左室电压及QTd变化存在时间因素与分组因素的交互效应（<i>P</i> < 0.05）；CLBBB组与对照组的JTcd比较差异有统计学意义（<i>P</i> < 0.05）；CLBBB组与对照组的左室电压在术后3 d和术后5 d组间比较差异有统计学意义（<i>P</i> < 0.05）。</AbstractText><AbstractText Label="结论">VSD患儿介入封堵术后有无CLBBB者早期心电图指标左室电压和JTcd有差异，其中JTcd可能对预测术后早期CLBBB的发生有参考作用。</AbstractText></OtherAbstract></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>6</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>6</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>9</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28606233</ArticleId><ArticleId IdType="pmc">PMC7390289</ArticleId><ArticleId IdType="pii">10.7499/j.issn.1008-8830.2017.06.010</ArticleId><ArticleId IdType="doi">10.7499/j.issn.1008-8830.2017.06.010</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Penny DJ, Vick GW 3rd. 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Survey of the effect of streptokinase on ventricular repolarization by examining the QT dispersion in patients with acute myocardial infraction in Seyed-Al-Shohada Hospital, Urmia. https://www.researchgate.net/publication/267754918_Survey_of_the_Effect_of_Streptokinase_on_Ventricular_Repolarization_by_Examining_the_QT_Dispersion_in_Patients_With_Acute_Myocardial_Infraction_in_Seyed-Al-Shohada_Hospital_Urmia/fulltext/55dfe4e808aecb1a7cc1b651/267754918_Survey_of_the_Effect_of_Streptokinase_on_Ventricular_Repolarization_by_Examining_the_QT_Dispersion_in_Patients_With_Acute_Myocardial_Infraction_in_Seyed-Al-Shohada_Hospital_Urmia.pdf Glob J Health Sci. 2014;6(7):74–82.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4796378</ArticleId><ArticleId IdType="pubmed">25363182</ArticleId></ArticleIdList></Reference><Reference><Citation>Bol Raap G, Meijboom FJ, Kappetein AP, et al. Long-term follow-up and quality of life after closure of ventricular septal defect in adults. Eur J Cardiothorac Surg. 2007;32(2):215–219. doi: 10.1016/j.ejcts.2007.04.023.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.ejcts.2007.04.023</ArticleId><ArticleId IdType="pubmed">17566753</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">28605368</PMID><DateCompleted><Year>2018</Year><Month>01</Month><Day>17</Day></DateCompleted><DateRevised><Year>2019</Year><Month>06</Month><Day>10</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>124</Issue><PubDate><Year>2017</Year><Month>Jun</Month><Day>04</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Murine Short Axis Ventricular Heart Slices for Electrophysiological Studies.
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Murine cardiomyocytes have been extensively used for in vitro studies of cardiac physiology and new therapeutic strategies. However, multicellular preparations of dissociated cardiomyocytes are not representative of the complex in vivo structure of cardiomyocytes, non-myocytes and extracellular matrix, which influences both mechanical and electrophysiological properties of the heart. Here we describe a technique to prepare viable ventricular slices of adult mouse hearts with a preserved in vivo like tissue structure, and demonstrate their suitability for electrophysiological recordings. After excision of the heart, ventricles are separated from the atria, perfused with Ca<sup>2+</sup>-free solution containing 2,3-butanedione monoxime and embedded in a 4% low-melt agarose block. The block is placed on a microtome with a vibrating blade, and tissue slices with a thickness of 150-400 µm are prepared keeping the vibration frequency of the blade at 60-70 Hz and moving the blade forward as slowly as possible. Thickness of the slices depends on the further application. Slices are stored in ice cold Tyrode's solution with 0.9 mM Ca<sup>2+</sup> and 2,3-butanedione monoxime (BDM) for 30 min. Afterwards, slices are transferred to 37 °C DMEM for 30 min to wash out the BDM. Slices can be used for electrophysiological studies with sharp electrodes or micro electrode arrays, for force measurements to analyze contractile function or to investigate the interaction of transplanted stem cell-derived cardiomyocytes and host tissue. For sharp electrode recordings, a slice is placed into a 3 cm cell culture dish on the heating plate of an inverted microscope. The slice is stimulated with a unipolar electrode, and intracellular action potentials of cardiomyocytes within the slice are recorded with a sharp glass electrode.
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ADAM10-Interacting Tetraspanins Tspan5 and Tspan17 Regulate VE-Cadherin Expression and Promote T Lymphocyte Transmigration.
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The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes. However, a definitive role for endothelial ADAM10 in transmigration of freshly isolated primary leukocytes under flow has not been demonstrated, and the relative importance of distinct ADAM10 substrates is unknown. Emerging evidence suggests that ADAM10 can be regarded as six different molecular scissors with different substrate specificities, depending on which of six TspanC8 tetraspanins it is associated with, but TspanC8s remain unstudied in leukocyte transmigration. In the current study, ADAM10 knockdown on primary HUVECs was found to impair transmigration of freshly isolated human peripheral blood T lymphocytes, but not neutrophils or B lymphocytes, in an in vitro flow assay. This impairment was due to delayed transmigration rather than a complete block, and was overcome in the presence of neutrophils. Transmigration of purified lymphocytes was dependent on ADAM10 regulation of VE-cadherin, but not CX3CL1 and CXCL16. Tspan5 and Tspan17, the two most closely related TspanC8s by sequence, were the only TspanC8s that regulated VE-cadherin expression and were required for lymphocyte transmigration. Therefore endothelial Tspan5- and Tspan17-ADAM10 complexes may regulate inflammation by maintaining normal VE-cadherin expression and promoting T lymphocyte transmigration.
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2,335,217 |
Bone morphogenetic protein signaling governs biliary-driven liver regeneration in zebrafish through tbx2b and id2a.
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Upon mild liver injury, new hepatocytes originate from preexisting hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe liver injury, biliary epithelial cells (BECs) contribute to new hepatocytes through BEC dedifferentiation into liver progenitor cells (LPCs), also termed oval cells or hepatoblast-like cells (HB-LCs), and subsequent differentiation into hepatocytes. Despite the identification of several factors regulating BEC dedifferentiation and activation, little is known about factors involved in the regulation of LPC differentiation into hepatocytes during liver regeneration. Using a zebrafish model of near-complete hepatocyte ablation, we show that bone morphogenetic protein (Bmp) signaling is required for BEC conversion to hepatocytes, particularly for LPC differentiation into hepatocytes. We found that severe liver injury led to the up-regulation of genes involved in Bmp signaling, including smad5, tbx2b, and id2a, in the liver. Bmp suppression did not block BEC dedifferentiation into HB-LCs; however, the differentiation of HB-LCs into hepatocytes was impaired due to the maintenance of HB-LCs in an undifferentiated state. Later Bmp suppression did not affect HB-LC differentiation but increased BEC number through proliferation. Notably, smad5, tbx2b, and id2a mutants exhibited similar liver regeneration defects as those observed in Bmp-suppressed livers. Moreover, BMP2 addition promoted the differentiation of a murine LPC line into hepatocytes in vitro.</AbstractText>Bmp signaling regulates BEC-driven liver regeneration through smad5, tbx2b, and id2a: it regulates HB-LC differentiation into hepatocytes through tbx2b and BEC proliferation through id2a; our findings provide insights into promoting innate liver regeneration as a novel therapy. (Hepatology 2017;66:1616-1630).</AbstractText>© 2017 by the American Association for the Study of Liver Diseases.</CopyrightInformation>
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2,335,218 |
No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine.
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It is currently recommended that hydroxychloroquine (HCQ) be maintained during pregnancy in patients with systemic lupus erythematosus. Recent data suggest that this Toll-like receptor inhibitor may also reduce the recurrence rate of anti-SSA/Ro associated congenital heart block (CHB). This case report describes a unique situation in which a CHB-afflicted, HCQ-exposed pregnancy was electively terminated. The heart did not reveal any characteristic features of cardiotoxicity, providing further evidence supporting the safety of foetal exposure to HCQ.
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2,335,219 |
Breast implant associated anaplastic large cell lymphoma: The UK experience. Recommendations on its management and implications for informed consent.
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Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare, Non-Hodgkin lymphoma arising in the capsule of breast implants. BIA-ALCL presents as a recurrent effusion and/or mass. Tumours exhibit CD30 expression and are negative for Anaplastic Lymphoma Kinase (ALK). We report the multi-disciplinary management of the UK series and how the stage of disease may be used to stratify treatment.</AbstractText>Between 2012 and 2016, 23 cases of BIA-ALCL were diagnosed in 15 regional centres throughout the UK. Data on breast implant surgeries, clinical features, treatment and follow-up were available for 18 patients.</AbstractText>The mean lead-time from initial implant insertion to diagnosis was 10 years (range: 3-16). All cases were observed in patients with textured breast implants or expanders. Fifteen patients with breast implants presented with stage I disease (capsule confined), and were treated with implant removal and capsulectomy. One patient received adjuvant chest-wall radiotherapy. Three patients presented with extra-capsular masses (stage IIA). In addition to explantation, capsulectomy and excision of the mass, all patients received neo-/adjuvant chemotherapy with CHOP as first line. One patient progressed on CHOP but achieved pathological complete response (pCR) with Brentuximab Vedotin. After a mean follow-up of 23 months (range: 1-56) all patients reported here remain disease-free.</AbstractText>BIA-ALCL is a rare neoplasm with a good prognosis. Our data support the recommendation that stage I disease be managed with surgery alone. Adjuvant chemotherapy may be required for more invasive disease and our experience has shown the efficacy of Brentuximab as a second line treatment.</AbstractText>Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.</CopyrightInformation>
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Prenatal exposure to antimalarials decreases the risk of cardiac but not non-cardiac neonatal lupus: a single-centre cohort study.
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Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus.</AbstractText>Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus.</AbstractText>A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR < 1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21).</AbstractText>In this large single-centre cohort study, exposure to AMs throughout pregnancy was associated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus.</AbstractText>© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]</CopyrightInformation>
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Recruitment of endosomal signaling mediates the forskolin modulation of guinea pig cardiac neuron excitability.
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Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein-coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60% of the cardiac neurons. The forskolin-mediated increase in excitability was considered related to cAMP regulation of a cyclic nucleotide gated channel or via protein kinase A (PKA)/ERK signaling, mechanisms that have been linked to PAC1 receptor activation. However, unlike PACAP mechanisms, forskolin enhancement of excitability was not significantly reduced by treatment with cesium to block currents through hyperpolarization-activated nonselective cation channels (<i>I</i><sub>h</sub>) or by treatment with PD98059 to block MEK/ERK signaling. In contrast, treatment with the clathrin inhibitor Pitstop2 or the dynamin inhibitor dynasore eliminated the forskolin-induced increase in excitability; treatments with the inactive Pitstop analog or PP2 treatment to inhibit Src-mediated endocytosis mechanisms were ineffective. The PKA inhibitor KT5702 significantly suppressed the forskolin-induced change in excitability; further, KT5702 and Pitstop2 reduced the forskolin-stimulated MEK/ERK activation in cardiac neurons. Collectively, the present results suggest that forskolin activation of AC/cAMP/PKA signaling leads to the recruitment of clathrin/dynamin-dependent endosomal transduction cascades, including MEK/ERK signaling, and that endosomal signaling is the critical mechanism underlying the forskolin-induced increase in cardiac neuron excitability.
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2,335,222 |
The effect of post-traumatic-stress-disorder on intra-operative analgesia in a veteran population during cataract procedures carried out using retrobulbar or topical anesthesia: a retrospective study.
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A growing proportion of veterans treated at the Veterans Health Administration (VA) have a history of post-traumatic-stress-disorder (PTSD), and there exists a higher rate of PTSD amongst veterans than the general population. The purpose of this study is to determine the correlation between PTSD and intra-operative analgesia, intra-operative time, and anesthesia type for cataract surgery in a veteran population. Secondary objectives are to determine if patient age, and first or second eye surgery affect intra-operative pain control or are correlated with type of anesthesia modality.</AbstractText>A retrospective study of 330 cataract surgeries performed by resident physicians between January and September 2012 at the Veterans Affairs Medical Center Tennessee Valley Healthcare System, Nashville and Murfreesboro Campuses was completed. Three hundred and thirty veteran patients were selected if their cataract surgery was performed between January and September 2012. Combined cases were excluded. The primary outcome evaluated was intra-operative analgesia. Secondary outcomes included history of post-traumatic-stress-disorder, anesthesia type, first or second eye, pain control, intra-operative heart rate and blood pressure, age, and case complexity. Data was analyzed using an unpaired two-sample Welch's t-test assuming unequal variance and Z test of comparison of proportions.</AbstractText>Patients with post-traumatic-stress-disorder reported higher pain scores, had longer operative times, and were more likely to have received a retrobulbar block. Operative time was not associated with an increased pain score, irrespective of anesthesia type, when controlled for PTSD. Complex cases had longer operative times, more sedation, and higher pain scores. P < 0.05 was used consistently.</AbstractText>Post-traumatic stress disorder and anxiety are more prevalent in the veteran population. Our data suggests that a history of post-traumatic-stress-disorder was correlated with higher pain scores, longer operative times, and with having received a retrobulbar block. Patients without a history of PTSD were more likely to have received topical anesthesia with or without sedation. The veteran population requires more sedation to allay anxiety and perceptions of discomfort, which may account for longer surgical times. The veteran population is a special population and it is important to investigate how PTSD in the veteran population affects intra-operative analgesia.</AbstractText>
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Developing a data-driven spatial approach to assessment of neighbourhood influences on the spatial distribution of myocardial infarction.
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There is a growing understanding of the role played by 'neighbourhood' in influencing health status. Various neighbourhood characteristics-such as socioeconomic environment, availability of amenities, and social cohesion, may be combined-and this could contribute to rising health inequalities. This study aims to combine a data-driven approach with clustering analysis techniques, to investigate neighbourhood characteristics that may explain the geographical distribution of the onset of myocardial infarction (MI) risk.</AbstractText>All MI events in patients aged 35-74 years occurring in the Strasbourg metropolitan area (SMA), from January 1, 2000 to December 31, 2007 were obtained from the Bas-Rhin coronary heart disease register. All cases were geocoded to the census block for the residential address. Each areal unit, characterized by contextual neighbourhood profile, included socioeconomic environment, availability of amenities (including leisure centres, libraries and parks, and transport) and psychosocial environment as well as specific annual rates standardized (per 100,000 inhabitants). A spatial scan statistic implemented in SaTScan was then used to identify statistically significant spatial clusters of high and low risk of MI.</AbstractText>MI incidence was non-randomly spatially distributed, with a cluster of high risk of MI in the northern part of the SMA [relative risk (RR) = 1.70, p = 0.001] and a cluster of low risk of MI located in the first and second periphery of SMA (RR 0.04, p value  =  0.001). Our findings suggest that the location of low MI risk is characterized by a high socioeconomic level and a low level of access to various amenities; conversely, the location of high MI risk is characterized by a high level of socioeconomic deprivation-despite the fact that inhabitants have good access to the local recreational and leisure infrastructure.</AbstractText>Our data-driven approach highlights how the different contextual dimensions were inter-combined in the SMA. Our spatial approach allowed us to identify the neighbourhood characteristics of inhabitants living within a cluster of high versus low MI risk. Therefore, spatial data-driven analyses of routinely-collected data georeferenced by various sources may serve to guide policymakers in defining and promoting targeted actions at fine spatial level.</AbstractText>
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2,335,224 |
Lyme carditis with complete heart block: management with an external pacemaker.
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Timely diagnosis and prompt initiation of treatment is essential in Lyme carditis to achieve favorable prognosis. Externalized permanent pacemaker with an active fixation lead as supportive pacing modality is a feasible option till complete resolution of conduction block with continued antibiotic therapy.
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2,335,225 |
Discordant disease expression of neonatal lupus erythematosus in twins.
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Neonatal lupus erythematosus is an autoimmune disease resulting from the trans-placental passage of maternal anti-SSA/Ro, anti-SSB/La, and less frequently anti-RNP antibodies to the foetus. At the time of diagnosis 50% of mothers are asymptomatic. Neonatal manifestations of this multisystem disease may include congenital heart block, cutaneous lesions and haematological abnormalities. We present the case of congenital neonatal lupus erythematosus in non-identical twins, showing variability in clinical manifestation of this disease,despite receiving the same level of antibodies from the mother. This case adds to the growing body of evidence about the role of genetics and other feto-maternal contributing factors in addition to the presence of auto antibodies. It raises interesting questions about discordant disease expression in offspring's of the same mother.
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2,335,226 |
Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca<sup>2+</sup> signaling in ventricular myocytes.
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Cyclic ADP-ribose (cADPR) releases Ca<sup>2+</sup> from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca<sup>2+</sup> (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca<sup>2+</sup> ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca<sup>2+</sup> increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.
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2,335,227 |
Experimental Sepsis Severity Score Associated to Mortality and Bacterial Spreading is Related to Bacterial Load and Inflammatory Profile of Different Tissues.
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Pneumonia-induced sepsis is responsible for about 50% of cases in the world. Patients who develop severe sepsis and septic shock present organ dysfunction and elevated plasma cytokine levels, which may lead to death. Clinical scores are important to evaluate the framework of septic patients and are used to predict the syndrome progress, prognostics, and mortality. The objective of the present study was to verify the applicability of a murine clinical score system to experimental sepsis (pneumonia-induced sepsis in male mice) and to correlate it with mortality and bacterial dissemination in different organs. Results demonstrated that animals which present higher clinical scores (>3) are more likely to die. Animals presenting high clinical scores exhibited transient bacteremia and displayed bacterial spreading to different organs such as heart, kidney, liver, and brain. There is a correlation between clinical score and bacterial dissemination and consequently greater risk of death. In addition, animals which showed bacterial dissemination in more than three organs and high clinical scores presented high levels of cytokines (TNF-α, MCP-1, IL-6, and IL-10) in plasma, lung, heart, liver, kidney, and brain. Therefore, our study suggests that (1) severity scores have predictive power in experimental models of sepsis and (2) high concentrations of tissue cytokines may contribute to localized inflammation and be one of the factors responsible for the systemic inflammatory syndrome of sepsis.
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2,335,228 |
PMicroRNA-124a regulates LPS-induced septic cardiac dysfunction by targeting STX2.
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To examine the role of miR-124a in LPS-induced septic cardiac insufficiency where underlying mechanism is unclear.</AbstractText>Expression of miR-124a was decreased in myocardium of LPS-induced septic cardiac dysfunction model. miR-124a antagomiR or agomiR were injected via tail vein to induce miR-124a-dysregulated model. miR-124a antagomiR aggravated LPS-induced cardiac dysfunction and apoptosis, while miR-124a agomiR had the opposite effect. Syntaxin-2 (STX2) was indicated as a candidate target gene by bioinformatic software. Further experiments confirmed that STX2 was downregulated in miR-124a agomiR-treated rats but upregulated in miR-124a antagomiR-treated rats, and STX2 inhibition could strongly block the miR-124a antagomiR-associated increase in cell apoptosis. Luciferase reporter activity assay indicated that STX2 was a direct target of miR-124a. Serological detection reveled that miR-124a was down-regulated in the plasma of septic cardiac dysfunction rats.</AbstractText>miR-124a aggravates LPS-induced cardiac dysfunction and the miR-124a/STX2 pathway might serve as the potential diagnostic and therapeutic targets for septic cardiac dysfunction.</AbstractText>
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2,335,229 |
Clinical trial of local anesthetic protocols for acute pain associated with caustic paste disbudding in dairy calves.
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Caustic paste disbudding is becoming more commonplace in North America. A large body of work has examined pain control for cautery disbudding and surgical dehorning, but fewer studies have evaluated pain control for caustic paste disbudding, and results conflict regarding benefits of local anesthesia. In humans, the pain associated with a caustic, chemical burn can differ in nature, duration, and intensity compared with a thermal burn. The objective of this clinical trial was to evaluate the effects of either a lidocaine cornual nerve block or a topical anesthetic incorporated into caustic paste on the acute pain of caustic paste disbudding. Seventy-two Holstein-Friesian calves housed in groups with an automated milk feeder were enrolled into 18 replicates balanced on age and assigned to 1 of 4 treatments: sham (S), placebo paste and a saline cornual block; topical (T), a novel caustic paste containing lidocaine and prilocaine, and a saline cornual block; cornual block (B), commercial caustic paste and a lidocaine cornual nerve block; and positive (P), commercial caustic paste and a saline cornual block. All calves received 0.5 mg/kg of meloxicam SC at the time of the block. Researchers were blinded to treatment group. Primary outcomes were validated pain behavior responses and pain sensitivity measured by algometry. Secondary outcomes consisted of respiratory and heart rate, latency to approach the evaluator, play behavior, feeding behavior, and standing and lying bout characteristics. Data were analyzed using linear, Poisson, and negative binomial regression models. Cornual-blocked calves had less pain sensitivity to 180 min after disbudding than all other groups; T and P calves had more pain sensitivity than S calves for the same time period. Compared with T and P calves, B and S calves had fewer pain behaviors until 120 min postdisbudding, decreased respiratory and heart rates, and a shorter latency to feed. The S calves exhibited more play behavior than other groups. Caustic paste appears to be acutely painful for at least 180 min, and this is reduced by a cornual nerve block but not by our novel paste. Because caustic paste may result in a different pain experience than cautery, use of a variety of metrics assessing affective state, physiologic responses, and normal behaviors, such as feeding and lying, should be included into future trials to help assess the welfare of calves disbudded by this method. We recommend that calves disbudded with caustic paste receive local anesthetic with a cornual nerve block as well as a nonsteroidal anti-inflammatory drug to mitigate acute pain.
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2,335,230 |
[Alternative approach to autonomic instability of very severe tetanus: stellate ganglion block].
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Tetanus is an acute and deadly disease caused by <i>Clostridium tetani</i>. A 60-year-old male came to hospital after he injured his thumb with a knife. Ten days later, he returned to hospital with abdominal spasms. He was vaccinated against tetanus and referred to intensive care unit. As he had sudden difficulty in respiration, he was entubated. Midazolam, magnesium and esmolol infusion were started. Next day, muscle spasms progressed all over his body. Midazolam infusion was replaced with propofol and vecuronium. At the third day, morphine infusion was added. At the 16<sup>th</sup> day, dexmedetomidine infusion was started. At the 20<sup>th</sup> day, ultrasound guided stellate ganglion block was performed to denervate sympathetic activity. The block was performed three times in a 10 days period. At the 30<sup>th</sup>, the patient recovered from very severe tetanus. The mainstay of tetanus treatment is adequate sedation. Neuroaxial blocks were proved to be effective for the control of sympathetic overactivity in recent years. Circulatory collapse remains to be the major cause of death. The mechanism is unclear but altered myocardial function is thought to be related to changeable catecholamine levels. The effect of stellate ganglion block on sympathetic and parasympathetic control of heart has been studied since the beginning of 1980s. Recently Scanlon et al. reported they treated a patient with medically refractory ventricular arrhythmias by ultrasound guided bilateral stellate ganglion block. In conclusion, stellate ganglion block can be an alternative method when the autonomic storm cannot be controlled with medical agents.<CopyrightInformation>Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Altıparmak</LastName><ForeName>Başak</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Muğla Sıtkı Koçman University Training and Research Hospital, Anesthesiology and Reanimation, Muğla, Turkey. Electronic address: [email protected].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uysal</LastName><ForeName>Ali İhsan</ForeName><Initials>Aİ</Initials><AffiliationInfo><Affiliation>Muğla Sıtkı Koçman University Training and Research Hospital, Anesthesiology and Reanimation, Muğla, Turkey.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yaşar</LastName><ForeName>Eylem</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Muğla Sıtkı Koçman University Training and Research Hospital, Anesthesiology and Reanimation, Muğla, Turkey.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Demirbilek</LastName><ForeName>Semra</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Muğla Sıtkı Koçman University Training and Research Hospital, Anesthesiology and Reanimation, Muğla, Turkey.</Affiliation></AffiliationInfo></Author></AuthorList><Language>por</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Abordagem alternativa para instabilidade autonômica no tétano muito grave: bloqueio do gânglio estrelado.</VernacularTitle><ArticleDate DateType="Electronic"><Year>2017</Year><Month>05</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>Brazil</Country><MedlineTA>Braz J Anesthesiol</MedlineTA><NlmUniqueID>101624623</NlmUniqueID><ISSNLinking>0104-0014</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001340" MajorTopicYN="Y">Autonomic Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001342" MajorTopicYN="N">Autonomic Nervous System Diseases</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013233" MajorTopicYN="Y">Stellate Ganglion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013742" MajorTopicYN="N">Tetanus</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="eng">Tetanus is an acute and deadly disease caused by Clostridium tetani. A 60-year-old male came to hospital after he injured his thumb with a knife. Ten days later, he returned to hospital with abdominal spasms. He was vaccinated against tetanus and referred to intensive care unit. As he had sudden difficulty in respiration, he was entubated. Midazolam, magnesium and esmolol infusion were started. Next day, muscle spasms progressed all over his body. Midazolam infusion was replaced with propofol and vecuronium. At the third day, morphine infusion was added. At the 16th day, dexmedetomidine infusion was started. At the 20<sup>th</sup> day, ultrasound guided stellate ganglion block was performed to denervate sympathetic activity. The block was performed three times in a 10 days period. At the 30<sup>th</sup> the patient recovered from very severe tetanus. The mainstay of tetanus treatment is adequate sedation. Neuroaxial blocks were proved to be effective for the control of sympathetic overactivity in recent years. Circulatory collapse remains to be the major cause of death. The mechanism is unclear but altered myocardial function is thought to be related to changeable catecholamine levels. The effect of stellate ganglion block on sympathetic and parasympathetic control of heart has been studied since the beginning of 1980s. Recently Scanlon et al. reported they treated a patient with medically refractory ventricular arrhythmias by ultrasound guided bilateral stellate ganglion block. In conclusion, stellate ganglion block can be an alternative method when the autonomic storm cannot be controlled with medical agents.
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2,335,231 |
Seasonal and time-of-day variations in acute non-image forming effects of illuminance level on performance, physiology, and subjective well-being.
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This study investigated seasonal and time-of-day dependent moderations in the strength and direction of acute diurnal non-image forming (NIF) effects of illuminance level on performance, physiology, and subjective well-being. Even though there are indications for temporal variations in NIF-responsiveness to bright light, scientific insights into potential moderations by season are scarce. We employed a 2 (Light: 165 versus 1700 lx at the eye level, within) × 2 (Season: autumn/winter versus spring, between) × 2 (Time of day: morning versus afternoon, between) mixed-model design. During each of the two 90-min experimental sessions, participants (autumn/winter: N = 34; spring: N = 39) completed four measurement blocks (incl. one baseline block of 120 lx at the eye level) each consisting of a Psychomotor Vigilance Task (PVT) and a Backwards Digit-Span Task (BDST) including easy trials (4-6 digits) and difficult trials (7-8 digits). Heart rate (HR) and skin conductance level (SCL) were measured continuously. At the end of each lighting condition, subjective sleepiness, vitality, and mood were measured. The results revealed a clear indication for significant Light * Season interaction effects on both subjective sleepiness and vitality, which appeared only during the morning sessions. Participants felt significantly more vital and less sleepy in winter, but not in spring during bright light exposure in the morning. In line with these subjective parameters, participants also showed significantly better PVT performance in the morning in autumn/winter, but not in spring upon bright light exposure. Surprisingly, for difficult working memory performance, the opposite was found, namely worse performance during bright light exposure in winter, but better performance when exposed to bright light in spring. The effects of bright versus regular light exposure on physiology were quite subtle and largely nonsignificant. Overall, it can be concluded that acute illuminance-induced NIF effects on subjective alertness and vitality as well as objectively measured vigilance in the morning are significantly moderated by season. Possibly, these greater illuminance-induced benefits during the morning sessions in autumn/winter compared to spring occurred due to increased responsiveness to bright light exposure as a function of a relatively low prior light dose in autumn/winter.
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2,335,232 |
Rotational alignment of femoral component with different methods in total knee arthroplasty: a randomized, controlled trial.
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Femoral component rotation (FCR) is one of the most important factors in total knee arthroplasty. In this prospective study, we used three different techniques for FCR and analyzed their accuracy with postoperative axial computed tomography (CT) images. We also evaluated effect of FCR to clinical outcome.</AbstractText>One hundred sixty-five patients were randomly allocated into three groups. In the measured resection group, FCR was set by externally rotating the axis 3° off the posterior femoral condylar axis. In the tensor group, a gap-tensioning device set at 20 lbf was used. In the block group, spacer blocks of various thicknesses were used. The FCR angle (FCRa) was measured on postoperative axial CT as an angle between the clinical transepicondylar and posterior condylar axes of the femoral component. Outliers were defined as FCRas deviated more than 3° either internally or externally. Postoperative 2 year clinical scores and knee range of motion were checked.</AbstractText>The tensor group had significantly better positioning of the femoral component to the neutral position compared with the measured resection group and the block group (mean FCRa: internal rotation 1.79, 0.43 and 2.63°, respectively, p < 0.001). The outliers were also least frequent in the tensor group (35, 16 and 40%, respectively, p = 0.02). There were no significant differences in postoperative 2 year clinical results among groups.</AbstractText>Gap technique with a 20-lbf tensor device was the most accurate and precise method for obtaining adequate FCR. Measured resection with 3° external rotation and gap technique with blocks could lead to internal rotation of the femoral component. Postoperative 2 year clinical results were not significantly different among groups with different techniques for FCR.</AbstractText>The study was registered in the Clinical Research information Service (trial number: KCT0000129 ) in Korea. Registration date is 23rd</sup> of June, 2011.</AbstractText>
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2,335,233 |
Fetal rhythm-based language discrimination: a biomagnetometry study.
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Using fetal biomagnetometry, this study measured changes in fetal heart rate to assess discrimination of two rhythmically different languages (English and Japanese). Two-minute passages in English and Japanese were read by the same female bilingual speaker. Twenty-four mother-fetus pairs (mean gestational age=35.5 weeks) participated. Fetal magnetocardiography was recorded while the participants were presented first with passage 1, a passage in English, and then, following an 18 min interval, with passage 2, either a different passage in English (English-English condition: N=12) or in Japanese (English-Japanese condition: N=12). The fetal magnetocardiogram was reconstructed following independent components analysis decomposition. The mean interbeat intervals were calculated for a 30 s baseline interval directly preceding each passage and for the first 30 s of each passage. We then subtracted the mean interbeat interval of the 30 s baseline interval from that of the first 30 s interval, yielding an interbeat interval change value for each passage. A significant interaction between condition and passage indicated that the English-Japanese condition elicited a more robust interbeat interval change for passage 2 (novelty phase) than for passage 1 (familiarity phase), reflecting a faster heart rate during passage 2, whereas the English-English condition did not. This effect indicates that fetuses are sensitive to the change in language from English to Japanese. These findings provide the first evidence for fetal language discrimination as assessed by fetal biomagnetometry and support the hypothesis that rhythm constitutes a prenatally available building block in language acquisition.
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2,335,234 |
Chemical End Group Modified Diblock Copolymers Elucidate Anchor and Chain Mechanism of Membrane Stabilization.
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Block copolymers can be synthesized in an array of architectures and compositions to yield diverse chemical properties. The triblock copolymer Poloxamer 188 (P188), the family archetype, consisting of a hydrophobic poly(propylene oxide) core flanked by hydrophilic poly(ethylene oxide) chains, can stabilize cellular membranes during stress. However, little is known regarding the molecular basis of membrane interaction by copolymers in living organisms. By leveraging diblock architectural design, discrete end-group chemistry modifications can be tested. Here we show evidence of an anchor and chain mechanism of interaction wherein titrating poly(propylene oxide) block end group hydrophobicity directly dictates membrane interaction and stabilization. These findings, obtained in cells and animals in vivo, together with molecular dynamics simulations, provide new insights into copolymer-membrane interactions and establish the diblock copolymer molecular architecture as a valuable platform to inform copolymer-biological membrane interactions. These results have implications for membrane stabilizers in muscular dystrophy and for other biological applications involving damaged cell membranes.
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2,335,235 |
Radiation Dose and Procedure Time for 994 CT-guided Spine Pain Control Procedures.
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Image guidance for spine pain control procedures, including epidural steroid injection, nerve root block, and facet block, can be performed with either computed tomography (CT) or conventional fluoroscopy. CT has the advantage of improved anatomic localization and use of air for contrast; however, there are concerns that CT leads to higher radiation dose and longer procedure time.</AbstractText>To evaluate procedure time and radiation dose for multiple types of spine pain control procedures performed under CT guidance.</AbstractText>Retrospective evaluation.</AbstractText>Department of radiology in single academic medical center.</AbstractText>Institutional review board approval was obtained. We reviewed CT-guided spine procedures performed over a 12-month period from January 2012 to December 2012. Procedure type, procedure time, and dose-length product were recorded. Patient age and gender were recorded for each case; additionally, demographic and medical history data were obtained for a sub-group of patients.</AbstractText>Nine hundred ninety-four studies (performed in 699 patients) were reviewed, including 585 epidural steroid injections, 228 nerve root blocks, and 90 facet blocks. For all studies, procedure time averaged 7:34 ± 5:05, and dose-length product averaged 75 mGy·cm ± 61. Additional medical history (available for 483 patients) revealed high rate of obesity (body mass index [BMI] = 30 ± 6.8, with 76% of patients overweight [BMI > 25] and 42% obese [BMI > 30]), and frequent medical comorbidities (including hypertension [n = 179], diabetes [n = 101], renal failure [n = 30], and heart failure [n = 17]).</AbstractText>This study was performed retrospectively, and limited to a single institution.</AbstractText>These findings add to the growing evidence that CT guidance is a safe and effective technique for epidural steroid injection. These results further demonstrate that other spine intervention procedures, including nerve root block and facet block, can also be performed under CT guidance with short procedure time and reasonable levels of radiation exposure. This approach can be effectively used in a patient population with a high rate of obesity and medical comorbidities.</AbstractText>
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2,335,236 |
Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia.
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Liver hepatocytes (Hep) are known to be central players during the inflammatory response to systemic infection. Interestingly, the protein tyrosine phosphatases (PTP) SHP-1, has been recognized as a major regulator of inflammation; however their implication in the control of Hep-mediated inflammatory response is still unknown. To study its implication in the regulation of the Hep-mediated inflammatory response during endotoxemia, Cre-Lox mice with a Hep-specific Ptpn6 deletion (Ptpn6 <sup>H-KO</sup> ) were injected with LPS. In contrast to the wild-type mice (Ptpn6 <sup>f/f</sup> ) that started to die by 24 hrs post-inoculation, the Ptpn6 <sup>H-KO</sup> mice exhibited mortality by 6 hrs. In parallel, higher amounts of metabolic markers, pro-inflammatory mediators and circulating cytokines were detected in Ptpn6 <sup>H-KO</sup> mice. Primary Hep obtained from Ptpn6 <sup>H-KO</sup> , also showed increased secretion of pro-inflammatory cytokines and nitric oxide (NO) comparatively to its wild type (Ptpn6 <sup>f/f</sup> ) counterpart. Pharmacological approaches to block TNF-α and NO production protected both the Ptpn6 <sup>f/f</sup> and the Ptpn6 <sup>H-KO</sup> mice against deadly LPS-mediated endotoxemia. Collectively, these results establish hepatocyte SHP-1 is a critical player regulating systemic inflammation. Our findings further suggest that SHP-1 activation could represent a new therapeutic avenue to better control inflammatory-related pathologies.
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2,335,237 |
Fetal and neonatal involvement in maternal rheumatologic disease.
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A pregnancy complicated with rheumatologic diseases can have various influences on the fetus and/or neonate. Maternal systemic lupus erythematosus (SLE) may cause preterm and/or small for gestational age (SGA) delivery and neonatal lupus (NL). Some neonates with NL have congenital heart block (CHB) with increased morbidity and mortality, even requiring pacemakers. Antiphospholipid syndrome may occur with SLE and affect fetal and/or neonatal outcomes. Pregnancy involving primary Sjögren's syndrome (pSS) tends to result in preterm delivery and low birthweight infants. Moreover, CHB is the most challenging complication for neonates delivered by women with pSS. Pregnant women with rheumatoid arthritis (RA) are at an increased risk for delivering a preterm or SGA neonate. In addition, RA drugs may have adverse effects on the fetus and breast-fed neonate. With dermatomyositis/polymyositis, pregnancies are at increased risk for spontaneous abortion, perinatal death, and preterm delivery. At present, overall neonatal survival rates are good for pregnancies involving systemic sclerosis, despite an increased frequency of premature and SGA neonates. In conclusion, maternal rheumatological diseases require careful monitoring to ensure the best possible management for fetal and neonatal outcomes.
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2,335,238 |
The Electrogenic Na<sup>+</sup>/K<sup>+</sup> Pump Is a Key Determinant of Repolarization Abnormality Susceptibility in Human Ventricular Cardiomyocytes: A Population-Based Simulation Study.
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<b>Background:</b> Cellular repolarization abnormalities occur unpredictably due to disease and drug effects, and can occur even in cardiomyocytes that exhibit normal action potentials (AP) under control conditions. Variability in ion channel densities may explain differences in this susceptibility to repolarization abnormalities. Here, we quantify the importance of key ionic mechanisms determining repolarization abnormalities following ionic block in human cardiomyocytes yielding normal APs under control conditions. <b>Methods and Results:</b> Sixty two AP recordings from non-diseased human heart preparations were used to construct a population of human ventricular models with normal APs and a wide range of ion channel densities. Multichannel ionic block was applied to investigate susceptibility to repolarization abnormalities. I<sub>Kr</sub> block was necessary for the development of repolarization abnormalities. Models that developed repolarization abnormalities over the widest range of blocks possessed low Na<sup>+</sup>/K<sup>+</sup> pump conductance below 50% of baseline, and I<sub>CaL</sub> conductance above 70% of baseline. Furthermore, I<sub>NaK</sub> made the second largest contribution to repolarizing current in control simulations and the largest contribution under 75% I<sub>Kr</sub> block. Reversing intracellular Na<sup>+</sup> overload caused by reduced I<sub>NaK</sub> was not sufficient to prevent abnormalities in models with low Na<sup>+</sup>/K<sup>+</sup> pump conductance, while returning Na<sup>+</sup>/K<sup>+</sup> pump conductance to normal substantially reduced abnormality occurrence, indicating I<sub>NaK</sub> is an important repolarization current. <b>Conclusions:</b> I<sub>NaK</sub> is an important determinant of repolarization abnormality susceptibility in human ventricular cardiomyocytes, through its contribution to repolarization current rather than homeostasis. While we found I<sub>Kr</sub> block to be necessary for repolarization abnormalities to occur, I<sub>NaK</sub> decrease, as in disease, may amplify the pro-arrhythmic risk of drug-induced I<sub>Kr</sub> block in humans.
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2,335,239 |
Is segmental epidural anaesthesia an optimal technique for patients undergoing percutaneous nephrolithotomy?
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Neuraxial anaesthesia has recently become popular for percutaneous nephrolithotomy (PCNL). We conducted a study comparing general anaesthesia (GA) with segmental (T6</sub>-T12</sub>) epidural anaesthesia (SEA) for PCNL with respect to anaesthesia and surgical characteristics.</AbstractText>Ninety American Society of Anesthesiologists Physical Status-I and II patients undergoing PCNL randomly received either GA or SEA. Overall patient satisfaction was the primary end point. Intraoperative haemodynamics, epidural block characteristics, post-operative pain, time to rescue analgesic, total analgesic consumption, discharge times from post-anaesthesia care unit, surgeon satisfaction scores and stone clearance were secondary end points. Parametric data were analysed by Student's t</i>-test while non-parametric data were compared with Mann-Whitney U-test.</AbstractText>Group SEA reported better patient satisfaction (P</i> = 0.005). Patients in group GA had significantly higher heart rates (P</i> = 0.0001) and comparable mean arterial pressures (P</i> = 0.24). Postoperatively, time to first rescue analgesic and total tramadol consumption was higher in Group GA (P</i> = 0.001). Group SEA had lower pain scores (P</i> = 0.001). Time to reach Aldrete's score of 9 was shorter in group SEA (P</i> = 0.0001). The incidence of nausea was higher in group GA (P</i> = 0.001); vomiting rates were comparable (P</i> = 0.15). One patient in group SEA developed bradycardia which was successfully treated. Eight patients (18%) had hypertensive episodes in group GA versus none in group SEA (P</i> = 0.0001). One patient in GA group had pleural injury and was managed with intercostal drain. Stone clearance and post-operative haemoglobin levels were comparable in both groups.</AbstractText>PCNL under SEA has a role in selected patients, for short duration surgery and in expert hands.</AbstractText>
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2,335,240 |
Multi-scale, tailor-made heart simulation can predict the effect of cardiac resynchronization therapy.
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The currently proposed criteria for identifying patients who would benefit from cardiac resynchronization therapy (CRT) still need to be optimized. A multi-scale heart simulation capable of reproducing the electrophysiology and mechanics of a beating heart may help resolve this problem. The objective of this retrospective study was to test the capability of patient-specific simulation models to reproduce the response to CRT by applying the latest multi-scale heart simulation technology.</AbstractText>We created patient-specific heart models with realistic three-dimensional morphology based on the clinical data recorded before treatment in nine patients with heart failure and conduction block treated by biventricular pacing. Each model was tailored to reproduce the surface electrocardiogram and hemodynamics of each patient in formats similar to those used in clinical practice, including electrocardiography (ECG), echocardiography, and hemodynamic measurements. We then performed CRT simulation on each heart model according to the actual pacing protocol and compared the results with the clinical data. CRT simulation improved the ECG index and diminished wall motion dyssynchrony in each patient. These results, however, did not correlate with the actual response. The best correlation was obtained between the maximum value of the time derivative of ventricular pressure (dP/dtmax</sub>) and the clinically observed improvement in the ejection fraction (EF) (r=0.94, p<0.01).</AbstractText>By integrating the complex pathophysiology of the heart, patient-specific, multi-scale heart simulation could successfully reproduce the response to CRT. With further verification, this technique could be a useful tool in clinical decision making.</AbstractText>Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
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2,335,241 |
High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block.
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Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB.</AbstractText>Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique.</AbstractText>Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids.</AbstractText>High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine.</AbstractText>© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.</CopyrightInformation>
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2,335,242 |
TGF-β<sub>1</sub> (Transforming Growth Factor-β<sub>1</sub>) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity.
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TGF-β1</sub> (transforming growth factor-β1</sub>) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β1</sub> alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro.</AbstractText>Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β1</sub>, applied for 24 to 48 hours at clinically relevant concentrations (≤2.5 ng/mL), causes substantial membrane depolarization concomitant with a several-fold increase of transmembrane currents. Transcriptome analysis revealed TGF-β1</sub>-dependent changes in 29 of 63 ion channel/pump/connexin transcripts, indicating a pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not affecting cardiomyocyte membrane potentials and cardiomyocyte-cardiomyocyte gap junctional coupling, TGF-β1</sub> depolarized cardiomyocytes coupled to myofibroblasts by ≈20 mV and increased gap junctional coupling between myofibroblasts and cardiomyocytes >5-fold as reflected by elevated connexin 43 and consortin transcripts. TGF-β1</sub>-dependent cardiomyocyte depolarization resulted from electrotonic crosstalk with myofibroblasts as demonstrated by immediate normalization of cardiomyocyte electrophysiology after targeted disruption of coupled myofibroblasts and by cessation of ectopic activity of cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic activity, block of TGF-β1</sub> signaling completely abolished both arrhythmogenic conditions.</AbstractText>TGF-β1</sub> profoundly alters the electrophysiological phenotype of cardiac myofibroblasts. Apart from possibly contributing to the control of cell function in general, the changes proved to be pivotal for proarrhythmic myofibroblast-cardiomyocyte crosstalk in vitro, which suggests that TGF-β1</sub> may play a potentially important role in arrhythmogenesis of the fibrotic heart.</AbstractText>© 2017 American Heart Association, Inc.</CopyrightInformation>
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2,335,243 |
Decreased Spontaneous Baroreflex Sensitivity as an Early Marker for Progression of Haemorrhage.
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Blood donation provides an ideal setup for assessment of cardiovascular responses to mild hypovolemia for understanding the underlying mechanisms.</AbstractText>To evaluate cardiovascular responses in time and magnitude by estimating the spontaneous baroreflex sensitivity (BRS) during and after donation of 450 ml of blood.</AbstractText>Continuous beat-to-beat blood pressure and lead II ECG was recorded before, during and after blood donation in 54 healthy volunteers (age 34.7 ± 5.08 years; weight 77.9 ± 8.20 kg), followed by offline analyses of baroreflex sensitivity.</AbstractText>The systolic, diastolic or mean blood pressures did not change during or after the blood donation. Decrease in pulse pressure and increase in heart rate was observed post donation. The spontaneous BRS decreased during [8.68 (6.038-12.69) ms/mmHg] and after blood donation [9.401 (6.396-11.59) ms/mmHg] as compared to the baseline [12.83 (6.884-18.18) ms/mmHg] with a significant decrease in α-HF on spectral analysis.</AbstractText>Mild blood loss (450 ml) results in non-hypotensive haemorrhage with a decrease in spontaneous BRS before the rise of heart rate during blood donation.</AbstractText>
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2,335,244 |
Retrobulbar Block in Pediatric Vitreoretinal Surgery Eliminates the Need for Intraoperative Fentanyl and Postoperative Analgesia: A Randomized Controlled Study.
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Pediatric ophthalmologic surgery is traditionally accomplished by general anesthesia with opioids, but respiratory depression remains a major concern. Our study compared the efficacy of retrobulbar block with systemic fentanyl on pain, hemodynamic, and stress response in pediatric vitreoretinal surgery.</AbstractText>A prospective double-blind, randomized controlled study was performed comparing retrobulbar block with intravenously administered fentanyl in 28 children aged 1 to 6 years undergoing vitreoretinal surgery. After general anesthesia was induced, retrobulbar block with 0.5% ropivacaine was accomplished in group RB (general anesthesia plus retrobulbar block) (n = 13), and normal saline was injected into retrobulbar space in group F (general anesthesia alone) (n = 15). Fentanyl 0.5 μg/kg was administered when signs of inadequate anesthesia were observed.</AbstractText>Respiratory depression (defined as a persistent respiratory rate <10 breaths/min or persistent oxygen desaturation <92%) was observed in 5 of 15 patients in group F after laryngeal mask airway was removed in the operating room, compared with none in group RB. All children in group F consumed intraoperative fentanyl rescue (average intraoperative fentanyl consumption, 1.3 ± 0.3 μg/kg) compared with none in group RB. Pain scores assessed with Faces, Legs, Activity, Cry and Consolability were significantly lower in group RB than in group F (1 [0, 3.5] vs 5 [3, 7], P = 0.003) immediately after laryngeal mask airway removal. Heart rate in group RB was significantly lower than that in group F before anesthesia induction, at the beginning and end of surgery, respectively. Mean blood pressure in group RB was significantly lower than that in group F at the beginning of surgery. Postoperative tumor necrosis factor α concentration in group RB was significantly lower than that in group F.</AbstractText>Retrobulbar block is safe and effective as an alternative to systemic fentanyl and could provide better pain management, hemodynamic suppression, and stress response suppression in pediatric vitreoretinal surgery.</AbstractText>
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2,335,245 |
Development of bioanalytical assays for variegin, a peptide-based bivalent direct thrombin inhibitor.
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Variegin is an anticoagulant peptide that will be tested in porcine models of percutaneous coronary intervention. We developed three bioanalytical assays for variegin quantitation and utilized these methods to evaluate pharmacokinetics of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8-5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half-lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic assays were 52.3 ± 4.4, 50.4 ± 5.9 and 67.7 ± 6.3 min, respectively.</AbstractText>We developed three bioanalytical assays for a novel direct thrombin inhibitor, variegin. The thrombin time assay is optimized for variegin quantitation during future porcine studies and clinical trials.</AbstractText>
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2,335,246 |
Some aspects of radical cascade and relay reactions.
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The ability to create carbon-carbon bonds is at the heart of organic synthesis. Radical processes are particularly apt at creating such bonds, especially in cascade or relay sequences where more than one bond is formed, allowing for a rapid assembly of complex structures. In the present brief overview, examples taken from the authors' laboratory will serve to illustrate the strategic impact of radical-based approaches on synthetic planning. Transformations involving nitrogen-centred radicals, electron transfer from metallic nickel and the reversible degenerative exchange of xanthates will be presented and discussed. The last method has proved to be a particularly powerful tool for the <i>intermolecular</i> creation of carbon-carbon bonds by radical additions even to unactivated alkenes. Various functional groups can be brought into the same molecule in a convergent manner and made to react together in order to further increase the structural complexity. One important benefit of this chemistry is the so-called RAFT/MADIX technology for the manufacture of block copolymers of almost any desired architecture.
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2,335,247 |
Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm (≤34 weeks) Neonates: A Randomized Controlled Trial.
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To compare the efficacy and safety of standard doses of Caffeine and Aminophylline for Apnea of prematurity.</AbstractText>Randomized controlled trial.</AbstractText>Tertiary-care referral centre and a teaching institution in Southern India. Trial was conducted from February 2012 to January 2015.</AbstractText>240 preterm (≤34 wk) neonates with apnea of prematurity.</AbstractText>Neonates randomized into two groups: Caffeine group received loading dose of caffeine citrate (20 mg/kg) followed by 5 mg/kg/day maintenance dose every 24 hour. Aminophylline group received loading dose of Aminophylline - 5 mg/kg and maintenance dose of 1.5 mg/kg 8-hourly.</AbstractText>Difference in apneic spells, associated respiratory morbidity, and acute adverse events were assessed. Association of efficacy with therapeutic drug levels was also evaluated.</AbstractText>Infants on aminophylline experienced less apnea spells in 4-7 days of therapy (P=0.03). Mean apnea rate and isolated desaturations were similar in 1-3, 4-7 and 8-14 days of therapy. No difference was noted in duration of Neonatal Intensive Care Unit stay and hospital stay. Mean heart rate was significantly high in Aminophylline group (P<0.001). Risk of developing tachycardia was less (RR 0.30; 95% CI range 0.15 to 0.60; P<0.001) in Caffeine- over Aminophylline-treated infants.</AbstractText>Aminophylline is as effective as caffeine for prevention of apneic spells in preterm neonates; however, dosage optimization needs to be done to reduce toxicity.</AbstractText>
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2,335,248 |
Idiopathic Pulmonary Fibrosis: Molecular Endotypes of Fibrosis Stratifying Existing and Emerging Therapies.
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Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown causes. Current diagnostic criteria are based on radiological, clinical, and histopathological features but, unfortunately, still many patients remain undiagnosed. Two currently approved therapies, pirfenidone and nintedanib, slow down disease progression but failed to block or revert it. On the other hand, many of the therapeutic agents tested in several clinical trials have not given satisfactory answers, probably due to the pathological heterogeneity of the disease. A growing number of studies show that IPF phenotype is the common clinical outcome of a variety of different pathophysiological mechanisms that identify disease subgroups characterised by specific genetic and molecular biomarkers (endotypes). The precision medicine approach is identifying and analysing the complex system of genetic, molecular, environmental, and behavioural variables underlying the development of the disease and the response to therapy. These molecular pathways are potential targets for novel agents and useful diagnostic, prognostic, and theragnostic biomarkers. We outline the status of knowledge in this field by discussing the complex pathogenetic pathways underlying different disease subgroups and assessing a stratification approach to novel therapeutic agents based on these endotypes.
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2,335,249 |
A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function.
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The transcription factor c-Myb is involved in early differentiation and proliferation of haematopoietic cells, where it operates as a regulator of self-renewal and multi-lineage differentiation. Deregulated c-Myb plays critical roles in leukaemias and other human cancers. Due to its role as a master regulator, we hypothesized it might function as a pioneer transcription factor. Our approach to test this was to analyse a mutant of c-Myb, D152V, previously reported to cause haematopoietic defects in mice by an unknown mechanism. Our transcriptome data from K562 cells indicates that this mutation specifically affects c-Myb's ability to regulate genes involved in differentiation, causing failure in c-Myb's ability to block differentiation. Furthermore, we see a major effect of this mutation in assays where chromatin opening is involved. We show that each repeat in the minimal DNA-binding domain of c-Myb binds to histones and that D152V disrupts histone binding of the third repeat. ATAC-seq data indicates this mutation impairs the ability of c-Myb to cause chromatin opening at specific sites. Taken together, our findings support that c-Myb acts as a pioneer factor and show that D152V impairs this function. The D152V mutant is the first mutant of a transcription factor specifically destroying pioneer factor function.
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2,335,250 |
Fabrication of Orientation-Controlled 3D Tissues Using a Layer-by-Layer Technique and 3D Printed a Thermoresponsive Gel Frame.
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Herein, we report the fabrication of orientation-controlled tissues similar to heart and nerve tissues using a cell accumulation and three-dimensional (3D) printing technique. We first evaluated the 3D shaping ability of hydroxybutyl chitosan (HBC), a thermoresponsive polymer, by using a robotic dispensing 3D printer. HBC polymer could be laminated to a height of 1124 ± 14 μm. Based on this result, we fabricated 3D gel frames of various shapes, such as square, triangular, rectangular, and circular, for shape control of 3D tissue and then normal human cardiac fibroblasts (NHCFs) coated with extracellular matrix nanofilms were seeded in the frames. Observation of shape-controlled tissues after 1 day of cultivation showed that the orientation of fibroblasts was in one direction when a short-sided, thin, rectangular-shaped frame was used. Next, we tried to fabricate orientation-controlled tissue with a vascular network by coculturing NHCF and normal human cardiac microvascular endothelial cells. As a consequence of cultivation for 4 days, observation of cocultured tissue confirmed aligned cells and blood capillaries in orientation-controlled tissue. Our results clearly demonstrated that it would be possible to control the cell orientation by controlling the shape of the tissues by combining a cell accumulation technique and a 3D printing system. The results of this study suggest promising strategies for the fabrication of oriented 3D tissues in vitro. These tissues, mimicking native organ structures, such as muscle and nerve tissue with a cell alignment structure, would be useful for tissue engineering, regenerative medicine, and pharmaceutical applications.
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2,335,251 |
Pacemaker syndrome with sub-acute left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker: consequence of lead switch at the header.
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In the daily practice of pacemaker insertion, the occurrence of atrial and ventricular lead switch at the pacemaker box header is a rare and unintentional phenomenon, with less than five cases reported in the literature. The lead switch may have dire consequences, depending on the indication for the pacemaker. One of these consequences is pacemaker syndrome, in which the normal sequence of atrial and ventricular activation is impaired, leading to sub-optimal ventricular filling and cardiac output. It is important for the attending physician to recognise any worsening of symptoms in a patient who has recently had a permanent pacemaker inserted. In the case of a dual-chamber pacemaker, switching of the atrial and ventricular leads at the pacemaker box header should be strongly suspected. We present an unusual case of pacemaker syndrome and right ventricular-only pacinginduced left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker.
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2,335,252 |
bFGF Protects Against Oxygen Glucose Deprivation/Reoxygenation-Induced Endothelial Monolayer Permeability via S1PR1-Dependent Mechanisms.
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Blood-brain barrier (BBB) disruption is a common pathological feature of many neurological disorders including stroke and brain trauma, therefore is an important therapeutic target for treatment of these diseases. Basic fibroblast growth factor (bFGF) as a member of FGF superfamily plays critical roles in angiogenesis, neurogenesis, and neuron survival. We recently showed that recombinant bFGF protects against BBB disruption in traumatic brain injury in mice. In this study, we further investigated the mechanisms of recombinant bFGF in BBB protection by measuring the permeability of cultured endothelial cell monolayer induced by oxygen-glucose deprivation and reoxygenation (OGD/R). We found that recombinant bFGF significantly decreased OGD/R-induced permeability of primary human brain microvascular endothelial cell (HBMEC) monolayer and preserved OGD/R-induced decreases of trans-endothelial electrical resistance (TEER). Western blot and immunocytochemistry showed that bFGF significantly rescued OGD/R-induced downregulation of junction proteins ZO-1, occludin, and VE-cadherin. We further show that the BBB protective effect of bFGF is via FGF receptor 1 (FGFR1) activation as FGFR1 inhibitor can block this protection effect. Moreover, we revealed that the BBB protection effect of bFGF is at least partially through rescuing the OGD/R-induced downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) protein, as S1PR1 inhibitor or SIPR1 small interfering RNA blocked the BBB protective effect of bFGF, whereas S1PR1 agonist alone has comparable BBB protection effect of bFGF. These findings will improve our understanding of the protective effect and mechanisms of bFGF on BBB and propose bFGF as a potential therapeutic agent against BBB damage in neurological disorders.
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2,335,253 |
A novel 'splice site' HCN4 Gene mutation, c.1737+1 G>T, causes familial bradycardia, reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability.
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The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome.</AbstractText>A novel c.1737+1 G>T 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart rate<60/min on resting ECG). Minimum [36 (SD 7) vs. 47 (SD 5) bpm, p=0.0087) and average heart rates [62 (SD 8) vs. 73 (SD 8) bpm, p=0.0168) were significantly lower in carriers on 24-hour Holter recordings. Under maximum exercise test carriers achieved significantly lower heart rates than non-carrier family members, and percent heart rate reserve and percent corrected heart rate reserve were significantly lower in carriers. Applying rigorous criteria for chronotropic incompetence a higher number of carriers exhibited chronotropic incompetence. Parameters, characterizing short-term variability of heart rate (i.e. rMSSD and pNN50%) were increased in carrier family members, even after normalization for heart rate, in the 24-hour ECG recordings with the same relative increase in 5-minute recordings.</AbstractText>The identified novel 'splice site' HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers.</AbstractText>Copyright © 2017 Elsevier B.V. All rights reserved.</CopyrightInformation>
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2,335,254 |
Chronic lithium intoxication: Varying electrocardiogram manifestations.
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Lithium is a commonly used drug in psychiatric practice. It is used in the treatment of depression and bipolar disorder. It has a narrow therapeutic index with documented adverse effects even near therapeutic levels. It has myriad of manifestations at toxic levels. The cardiovascular effects range from relatively benign ST-T wave changes to fatal arrhythmias. We describe a case of lithium toxicity which presented as a junctional rhythm and later showed a variety of manifestations such as complete heart block, atrial fibrillation, sinus bradycardia, and finally reverted to sinus rhythm at par with serum lithium levels.
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2,335,255 |
Long term effects of cilostazol in a dog with sick sinus syndrome.
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Sick sinus syndrome (SSS) is a type of bradyarrhythmia that can lead to syncope. Cilostazol has been reported to be an effective treatment for human patients with SSS and other bradyarrhythmias. This report describes the successful long-term treatment with cilostazol in a dog with SSS. A nine-year old intact male Miniature Schnauzer presented with a history of syncopal episodes and unsteady gait. After cilostazol treatment, the total heart rate (HR), mean HR, and frequency of premature ventricular contractions (PVCs) increased, while the maximum HR and maximum pause time decreased. Additionally, the number of syncopal episodes decreased. The dog died suddenly, 1,418 days after the start of cilostazol treatment. Cilostazol may be a useful therapeutic agent in canines with SSS.
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2,335,256 |
Downregulation of PI3K-γ in a mouse model of sepsis-induced myocardial dysfunction.
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A key component during sepsis is the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, of which the PI3K-γ isoform is a major regulator in many inflammatory responses. However, the role of PI3K-γ in the development of sepsis-induced myocardial dysfunction (SIMD) is unknown. In this study, we established a model of SIMD induced by lipopolysaccharide (LPS), subsequently used the selective inhibitor LY294002 and AS605240 to block the effect of PI3K and PI3K-γ, respectively. Cardiac function was evaluated by echocardiography, hearts were obtained for histological and protein expression examinations. ELISA was used to measure the serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), cardiac troponin I (cTnI) and heart-type fatty acid binding protein (H-FABP). LPS-treated mice showed an increase to cardiac inflammation, myocardial damage and production of TNF-α, IL-6, NF-κB, cTnI and H-FABP. Administration of AS605240 to LPS-treated mice reduced some patho-physiological characteristics of SIMD and reduced TNF-α, IL-6, cTnI and H-FABP production. However, administration of LY294002 did not improve those same conditions. The results showed that PI3K-γ is likely a crucial element in SIMD by regulating the PI3K/Akt pathway, and become a new marker of myocardial injury. Inhibition of PI3K-γ might be a potential therapeutic target in SIMD.
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2,335,257 |
A reconfigurable cryogenic platform for the classical control of quantum processors.
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The implementation of a classical control infrastructure for large-scale quantum computers is challenging due to the need for integration and processing time, which is constrained by coherence time. We propose a cryogenic reconfigurable platform as the heart of the control infrastructure implementing the digital error-correction control loop. The platform is implemented on a field-programmable gate array (FPGA) that supports the functionality required by several qubit technologies and that can operate close to the physical qubits over a temperature range from 4 K to 300 K. This work focuses on the extensive characterization of the electronic platform over this temperature range. All major FPGA building blocks (such as look-up tables (LUTs), carry chains (CARRY4), mixed-mode clock manager (MMCM), phase-locked loop (PLL), block random access memory, and IDELAY2 (programmable delay element)) operate correctly and the logic speed is very stable. The logic speed of LUTs and CARRY4 changes less then 5%, whereas the jitter of MMCM and PLL clock managers is reduced by 20%. The stability is finally demonstrated by operating an integrated 1.2 GSa/s analog-to-digital converter (ADC) with a relatively stable performance over temperature. The ADCs effective number of bits drops from 6 to 4.5 bits when operating at 15 K.
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2,335,258 |
Administration of Dexrazoxane Improves Cardiac Indices in Children and Young Adults With Acute Myeloid Leukemia (AML) While Maintaining Survival Outcomes.
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Anthracycline-induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane before anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages, 0 to 21 y) who received or did not receive dexrazoxane during the years 2008 to 2013. In total, 44 patients with AML (ages, 4.5 mo to 21.7 y) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, P=0.41) or 2-year overall survival (69% vs. 69%, P=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (P=0.0262) and shortening fraction (P=0.0381) trended significantly higher in patients that received dexrazoxane compared with those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane before anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or overall survival relative to institutional controls and seems to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.
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2,335,259 |
Effect of ephedrine combined with bupivacaine on maternal hemodynamic and spinal nerve block in cesarean delivery.
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The aim of the study was to investigate the effects of ephedrine intrathecal injection on maternal thermodynamics and spinal nerve block in cesarean section. A total of 107 patients undergoing elective cesarean section under combined spinal epidural anesthesia were randomly divided into two groups: group E: Bupivacaine (6 mg) combined with ephedrine (15 mg) and group C: Bupivacaine (6 mg). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), the incidence of hypotension, hypertension, tachycardia, nausea and vomiting were all recorded. The umbilical vein blood gases and noradrenaline, as well as maternal peripheral venous blood were analyzed. The time of high-quality spinal block was also recorded. Postoperatively, 1 day, 2 days bedside follow-up and 7, 21, 35 days telephone follow-up were carried out to determine any neurological deficit maternal performance. SBP and DBP decreased in group C but not in group E at 3 min after spinal anesthesia and 1 min after delivery (P<0.05). From 3 min post-anesthesia to the end of surgery, the HR levels in the C group were significantly higher than those of the E group (P<0.05). The incidence of hypotension, tachycardia, nausea and vomiting and neonate acidosis was low in group E compared with group C (P<0.05). The time of high-quality spinal block in group E was longer than that of group C (P<0.05). After spinal anesthesia, the concentration of noradrenaline from maternal peripheral venous blood was low in group C but high in group E compared with before spinal anesthesia (P<0.05). Ephedrine combined with low-dose bupivacaine intrathecal injection effectively maintained maternal hemodynamics and prolonged the time of sensory spinal block.
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2,335,260 |
A Randomized Controlled Trial Study on the Effect of Adding Dexmedetomidine to Bupivacaine in Supraclavicular Block Using Ultrasound Guidance.
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The benefits of regional anesthetic techniques are well established. Use of additives to local anesthetics can prolong these benefits. The aim of this study was to find out the effect of adding dexmedetomidine to bupivacaine for supraclavicular block.</AbstractText>In this randomized, double-blind study, 70 ASA I & II patients of either sex undergoing elective surgeries on the upper limb were given supraclavicular block under ultrasound guidance. Group C (n=35) received 38 mL 0.25% bupivacaine + 2mL normal saline and group D received 38 mL 0.25% bupivacaine + 1 µg/kg dexmedetomidine (2mL). Patients were observed for, onset of motor and sensory block, duration of motor and sensory block, duration of analgesia, sedation score, hemodynamic changes and any adverse events.</AbstractText>In group D, the onset was faster (P< 0.001), durations of sensory and motor block duration of and analgesia were prolonged as compared to group C (P < 0.0001).There was a significant drop in heart rate (HR) from the baseline in group D (P < 0.05) at 30, 60, 90 and 120 min. However, none of the patients dropped HR below 50/min. Mean Arterial Pressure (MAP) remained unaffected. The patients in group D were more effectively sedated than those in group C (P < 0.05). No adverse event was reported in either group.</AbstractText>Dexmedetomidine as adjuvant to bupivacaine in supraclavicular block resulted in faster action, prolonged motor and sensory block, prolonged analgesia with hemodynamic stability and adequate sedation.</AbstractText>
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2,335,261 |
Parameter inference for stochastic single-cell dynamics from lineage tree data.
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With the advance of experimental techniques such as time-lapse fluorescence microscopy, the availability of single-cell trajectory data has vastly increased, and so has the demand for computational methods suitable for parameter inference with this type of data. Most of currently available methods treat single-cell trajectories independently, ignoring the mother-daughter relationships and the information provided by the population structure. However, this information is essential if a process of interest happens at cell division, or if it evolves slowly compared to the duration of the cell cycle.</AbstractText>In this work, we propose a Bayesian framework for parameter inference on single-cell time-lapse data from lineage trees. Our method relies on a combination of Sequential Monte Carlo for approximating the parameter likelihood function and Markov Chain Monte Carlo for parameter exploration. We demonstrate our inference framework on two simple examples in which the lineage tree information is crucial: one in which the cell phenotype can only switch at cell division and another where the cell state fluctuates slowly over timescales that extend well beyond the cell-cycle duration.</AbstractText>There exist several examples of biological processes, such as stem cell fate decisions or epigenetically controlled phase variation in bacteria, where the cell ancestry is expected to contain important information about the underlying system dynamics. Parameter inference methods that discard this information are expected to perform poorly for such type of processes. Our method provides a simple and computationally efficient way to take into account single-cell lineage tree data for the purpose of parameter inference and serves as a starting point for the development of more sophisticated and powerful approaches in the future.</AbstractText>
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2,335,262 |
Effects of immunocastration and β-adrenergic agonists on the performance and carcass traits of feedlot finished Nellore cattle.
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β-Adrenergic agonists (β-AA) are non-hormonal growth promoters which promote muscle hypertrophy in supplemented animals. The effects of two β-AA in combination with the immunocastration technique on the performance and carcass traits were evaluated using 96 feedlot Nellore males in a randomized complete block design with two sex conditions (immunocastrated (IC) v. non-castrated (NC)) and three treatments: CON (no β-agonists added), RH (300 mg of ractopamine hydrochloride/day, for 33 days) or ZH (80 mg of zilpaterol·hydrochloride animal/day for 30 days, removed 3 days for required withdrawal period). The trial was carried for 100 days where in the first 70 days animals did not receive β-AA (phase 1) and during the last 30 days they were treated with β-AA (phase 2). The performance and ultrasound measurements of longissimus muscle area (LMA), backfat thickness (BFT) and rump fat thickness (RFT) were evaluated in both phases. No sex condition v. treatment interactions were observed for any trait. The NC animals had higher average daily gain (ADG) and final BW than the IC animals, but they did not differ in dry matter intake (DMI) and feed efficiency (gain to feed). The NC animals showed greater LMA (P=0.0001) and hot carcass weight (P=0.0006), and smaller BFT (P=0.0007), RFT (P=0.0039) and percentage of kidney, pelvic and heart fat (P<0.0001) when compared with IC animals. The animals fed ZH showed greater ADG (P=0.0002), G : F (P<0.0001) and dressing per cent (P=0.0136) than those fed RH and CON diets. No differences in BW and DMI were observed. A interaction between treatment and time on feed was observed for LMA and BFT, in which the animals fed ZH diet showed greater LMA (P<0.01) and lower BFT (P<0.01) at 100 days than the animals fed RH and CON diets, whereas RH and CON diets did not differ. Immunocastration decreases muscle development and increases carcass finishing. In contrast, β-AA increases muscle and decreases fat deposition. The ZH has a higher action on the muscle metabolism than animals fed RH diet. However, RH diet achieves a better balance because it has an intermediary performance between non-supplemented and ZH animals and does not decrease the carcass fat.
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2,335,263 |
Leg elevation decreases the incidence of post-spinal hypotension in cesarean section: a randomized controlled trial.
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Maternal hypotension is a common complication after spinal anesthesia for cesarean section (CS). In this study we investigated the role of leg elevation (LE) as a method for prevention of post-spinal hypotension (PSH) for cesarean section.</AbstractText>One hundred and fifty full term parturients scheduled for CS were included in the study. Patients were randomized into two groups: Group LE (leg elevation group, n = 75) and group C (Control group, n = 75). Spinal block was performed in sitting position after administration of 10 mL/Kg Ringer's lactate as fluid preload. After successful intrathecal injection of local anesthetic, Patients were positioned in the supine position. Leg elevation was performed for LE group directly after spinal anesthesia and maintained till skin incision. Intraoperative hemodynamic parameters (Arterial blood pressure and heart rate), intra-operative ephedrine consumption, incidence of PSH, and incidence of nausea and vomiting were reported.</AbstractText>LE group showed lower incidence of PSH (34.7% Vs 58.7%, P = 0.005) compared to the control group. Arterial blood pressure was higher in the LE group compared to the control group in the first two readings after spinal block. Other readings showed comparable arterial blood pressure and heart rate values between both study groups; however, LE showed less ephedrine consumption (4.9 ± 7.8 mg Vs 10 ± 11 mg, P = 0.001).</AbstractText>LE performed immediately after spinal block reduced the incidence of PSH in parturients undergoing CS.</AbstractText>The study was registered at Pan African Clinical Trials Registry system on 5/10/2015 with trial number PACTR201510001295348 .</AbstractText>
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2,335,264 |
Integrated optical force sensors using focusing photonic crystal arrays.
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Mechanical oscillators are at the heart of many sensor applications. Recently several groups have developed oscillators that are probed optically, fabricated from high-stress silicon nitride films. They exhibit outstanding force sensitivities of a few aN/Hz<sup>1/2</sup> and can also be made highly reflective, for efficient detection. The optical read-out usually requires complex experimental setups, including positioning stages and bulky cavities, making them impractical for real applications. In this paper we propose a novel way of building fully integrated all-optical force sensors based on low-loss silicon nitride mechanical resonators with a photonic crystal reflector. We can circumvent previous limitations in stability and complexity by simulating a suspended focusing photonic crystal, purely made of silicon nitride. Our design allows for an all integrated sensor, built out of a single block that integrates a full Fabry-Pérot cavity, without the need for assembly or alignment. The presented simulations will allow for a radical simplification of sensors based on high-Q silicon nitride membranes. Our results comprise, to the best of our knowledge, the first simulations of a focusing mirror made from a mechanically suspended flat membrane with subwavelength thickness. Cavity lengths between a few hundred µm and mm should be directly realizable.
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2,335,265 |
Dynamic modeling and network approaches for omics time course data: overview of computational approaches and applications.
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Inferring networks and dynamics of genes, proteins, cells and other biological entities from high-throughput biological omics data is a central and challenging issue in computational and systems biology. This is essential for understanding the complexity of human health, disease susceptibility and pathogenesis for Predictive, Preventive, Personalized and Participatory (P4) system and precision medicine. The delineation of the possible interactions of all genes/proteins in a genome/proteome is a task for which conventional experimental techniques are ill suited. Urgently needed are rapid and inexpensive computational and statistical methods that can identify interacting candidate disease genes or drug targets out of thousands that can be further investigated or validated by experimentations. Moreover, identifying biological dynamic systems, and simultaneously estimating the important kinetic structural and functional parameters, which may not be experimentally accessible could be important directions for drug-disease-gene network studies. In this article, we present an overview and comparison of recent developments of dynamic modeling and network approaches for time-course omics data, and their applications to various biological systems, health conditions and disease statuses. Moreover, various data reduction and analytical schemes ranging from mathematical to computational to statistical methods are compared including their merits, drawbacks and limitations. The most recent software, associated web resources and other potentials for the compared methods are also presented and discussed in detail.
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2,335,266 |
Causes of interruptions in postoperative enteral nutrition in children with congenital heart disease.
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Perioperative nutritional support has become a hot topic in the clinical management of congenital heart disease (CHD). Postoperative enteral nutrition (EN) offers many benefits, such as protection of the intestinal mucosa, reduced risk of infection, and low clinical costs. Interruptions in EN frequently influence nutritional support and clinical outcomes. We, therefore, aimed to determine the causes of interruptions in postoperative EN in CHD patients and discuss clinical counter measures.</AbstractText>We analyzed the data of 360 CHD patients to determine the causes of interruptions in postoperative EN and develop possible clinical strategies to prevent such interruptions.</AbstractText>Of the 360 patients (aged from 1 month to 6 years), 198 patients had at least one EN interruption. The total number of interruptions was 498 (average, 2.52 interruptions/ patient). Non-gastrointestinal factors (airway management, fluid overload, invasive procedure, increased intracranial pressure, feeding tube block, and clinical deterioration) accounted for 67.8% (338/498) of all interruptions and gastrointestinal factors (vomiting, gastrointestinal bleeding, diarrhea, constipation, and large gastric residual volume) accounted for 32.2% (160/498). The total number of interruptions and the number of interruptions due to gastrointestinal factors were significantly higher in younger patients (aged from 1-12 months) than in older patients (aged from 1-6 years).</AbstractText>Non-gastrointestinal factors were the main causes of interruptions in postoperative EN in CHD patients. Younger patients had a greater number of interruptions as a whole, and more interruptions caused by gastrointestinal factors. Gastrointestinal factors can be reduced by tube feeding and use of gastrointestinal motility drugs.</AbstractText>
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2,335,267 |
Perioperative Outcomes and Safety of Atrial Fibrillation Catheter Ablation in Octogenarians: A Retrospective Study and Review of the Benefits of Rhythm Control.
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Catheter ablation for rhythm control has emerged as a successful therapeutic option for the treatment of atrial fibrillation (AF), though it has not been well studied in octogenarians. This study evaluates its safety in octogenarians in a community hospital and reviews the benefits of rhythm control.</AbstractText>Among 1,592 patients undergoing AF ablation, 84 octogenarian were identified. The primary outcome was normal sinus rhythm (NSR) on electrocardiogram at discharge. Secondary outcomes were periprocedural complications and markers and risks of reablation compared to younger cohorts.</AbstractText>An NSR on discharge occurred in 83 patients. Three patients required pacing for symptomatic sinus bradycardia, complete heart block, and symptomatic junctional bradycardia, respectively. Reablation for recurrent AF occurred in 23 octogenarians. Using the octogenarians as reference, the relative risk (RR) of 1 reablation was not significantly different among the age groups 70-79, 60-69, and <60 years. The RR of 2 reablations was greater in the octogenarian group (RR 0.26 [95% CI 0.09-0.71, p = 0.008], 0.42 [95% CI 0.17-1.04, p = 0.06], and 0.27 [95% CI 0.1-0.75, p = 0.01], respectively). Coronary artery disease (OR 0.14, 95% CI 0.02-0.68, p = 0.026) and percutaneous coronary intervention (OR 0.13, 95% CI 0.02-0.63, p = 0.021) were markers for reablation.</AbstractText>AF catheter ablation achieved an NSR with minimal periprocedural complications. The benefits of rhythm control should be considered in treatment.</AbstractText>© 2017 S. Karger AG, Basel.</CopyrightInformation>
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2,335,268 |
Reliability of pressure waveform analysis to determine correct epidural needle placement in labouring women.
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Pressure waveform analysis provides a reliable confirmatory adjunct to the loss-of-resistance technique to identify the epidural space during thoracic epidural anaesthesia, but its role remains controversial in lumbar epidural analgesia during labour. We performed an observational study in 100 labouring women of the sensitivity and specificity of waveform analysis to determine the correct location of the epidural needle. After obtaining loss-of-resistance, the anaesthetist injected 5 ml saline through the epidural needle (accounting for the volume already used in the loss-of-resistance). Sterile extension tubing, connected to a pressure transducer, was attached to the needle. An investigator determined the presence or absence of a pulsatile waveform, synchronised with the heart rate, on a monitor screen that was not in the view of the anaesthetist or the parturient. A bolus of 4 ml lidocaine 2% with adrenaline 5 μg.ml<sup>-1</sup> was administered, and the epidural block was assessed after 15 min. Three women displayed no sensory block at 15 min. The results showed: epidural block present, epidural waveform present 93; epidural block absent, epidural waveform absent 2; epidural block present, epidural waveform absent 4; epidural block absent, epidural waveform present 1. Compared with the use of a local anaesthetic bolus to ascertain the epidural space, the sensitivity, specificity, positive and negative predictive values of waveform analysis were 95.9%, 66.7%, 98.9% and 33.3%, respectively. Epidural waveform analysis provides a simple adjunct to loss-of-resistance for confirming needle placement during performance of obstetric epidurals, however, further studies are required before its routine implementation in clinical practice.
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2,335,269 |
Sufficient explanation of management affects patient satisfaction and the practice of post-treatment management in spinal pain, a multicenter study of 1007 patients.
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Spinal pain is most common symptom in pain clinic. In most cases, before the treatment of spinal pain, physician explains the patient's disease and treatment. We investigated patient's satisfaction and physician's explanation related to treatments in spinal pain patients by questionnaires.</AbstractText>Anonymous questionnaires about physician's explanation and patient's satisfaction in each treatment and post-treatment management were asked to individuals suffering from spinal pain. Patients who have spinal pain were participated in our survey of nationwide university hospitals in Korea. The relationships between patient's satisfaction and other factors were analyzed.</AbstractText>Between June 2016 and August 2016, 1007 patients in 37 university hospitals completed the questionnaire. In the statistical analysis, patient's satisfaction of treatment increased when pain severity was low or received sufficient preceding explanation about nerve block and medication (P</i> < 0.01). Sufficient explanation increased patient's necessity of a post-treatment management and patients' performance rate of post-treatment management (P</i> < 0.01).</AbstractText>These results show that sufficient explanation increased patients' satisfaction after nerve block and medication. Sufficient explanation also increased the practice of patients' post-treatment management.</AbstractText>
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2,335,270 |
Effects of scalp block with bupivacaine versus levobupivacaine on haemodynamic response to head pinning and comparative efficacies in postoperative analgesia: A randomized controlled trial.
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Objective This study was performed to determine the effects of scalp blocks with bupivacaine versus levobupivacaine on the haemodynamic response during craniotomy and the efficacies and analgesic requirements of these drugs postoperatively. Methods This randomized, prospective, placebo-controlled, double-blind study included 90 patients (age, 18-85 years; American Society of Anesthesiologists physical status, I or II). The patients were randomly divided into three groups: those who received 20 mL of 0.5% bupivacaine (Group B, n = 30), 20 mL of 0.5% levobupivacaine (Group L, n = 30), or saline as a placebo (Group C, n = 30). Scalp blocks were performed 5 min before head pinning. The primary outcome was the mean arterial pressure (MAP), and the secondary outcomes were the heart rate (HR), visual analogue scale (VAS) scores, and additional intraoperative and postoperative drug use. Postoperative pain was evaluated using a 10-cm VAS. Results During head pinning and incision, the MAP and HR were significantly higher in Group C. The additional drug requirement for intraoperative hypertension and tachycardia was significantly higher in Group C. There were no significant differences in MAP, HR, or VAS scores between Groups B and L. Conclusion Both bupivacaine and levobupivacaine can be effectively and safely used for scalp blocks to control haemodynamic responses and postoperative pain.
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2,335,271 |
Inhibition of iron overload-induced apoptosis and necrosis of bone marrow mesenchymal stem cells by melatonin.
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Iron overload induces severe damage to several vital organs such as the liver, heart and bone, and thus contributes to the dysfunction of these organs. The aim of this study is to investigate whether iron overload causes the apoptosis and necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent its toxicity. Perls' Prussion blue staining showed that exposure to increased concentrations of ferric ammonium citrate (FAC) induced a gradual increase of intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC decreased the viability of BMSCs in a concentration-dependent manner. Notably, melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore, melatonin pretreatment suppressed FAC-induced reactive oxygen species accumulation. Western blot showed that exposure to FAC resulted in the decrease of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were significantly inhibited by melatonin treatment. At last, melatonin receptor blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis by melatonin. Taken together, melatonin protected BMSCs from iron overload induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1 and RIP3 pathways.
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2,335,272 |
Transformation diffusion reconstruction of three-dimensional histology volumes from two-dimensional image stacks.
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Traditional histology is the gold standard for tissue studies, but it is intrinsically reliant on two-dimensional (2D) images. Study of volumetric tissue samples such as whole hearts produces a stack of misaligned and distorted 2D images that need to be reconstructed to recover a congruent volume with the original sample's shape. In this paper, we develop a mathematical framework called Transformation Diffusion (TD) for stack alignment refinement as a solution to the heat diffusion equation. This general framework does not require contour segmentation, is independent of the registration method used, and is trivially parallelizable. After the first stack sweep, we also replace registration operations by operations in the space of transformations, several orders of magnitude faster and less memory-consuming. Implementing TD with operations in the space of transformations produces our Transformation Diffusion Reconstruction (TDR) algorithm, applicable to general transformations that are closed under inversion and composition. In particular, we provide formulas for translation and affine transformations. We also propose an Approximated TDR (ATDR) algorithm that extends the same principles to tensor-product B-spline transformations. Using TDR and ATDR, we reconstruct a full mouse heart at pixel size 0.92µm×0.92µm, cut 10µm thick, spaced 20µm (84G). Our algorithms employ only local information from transformations between neighboring slices, but the TD framework allows theoretical analysis of the refinement as applying a global Gaussian low-pass filter to the unknown stack misalignments. We also show that reconstruction without an external reference produces large shape artifacts in a cardiac specimen while still optimizing slice-to-slice alignment. To overcome this problem, we use a pre-cutting blockface imaging process previously developed by our group that takes advantage of Brewster's angle and a polarizer to capture the outline of only the topmost layer of wax in the block containing embedded tissue for histological sectioning.
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2,335,273 |
Allostery modulates the beat rate of a cardiac pacemaker.
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The S672R mutation in heart cell ion channels leads to low heart rates and arrhythmia by an unknown route. A multifaceted NMR analysis now demonstrates that this mutant impacts allosteric coupling in domains inside of the cell to change channel activation, providing a mechanistic explanation for phenotypic outcomes.
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2,335,274 |
20-Year Trend of CVD Risk Factors: Urban and Rural National Capital Region of India.
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The World Health Organization and the Government of India have set targets to reduce burden of noncommunicable diseases. Information on population level trend of risk factors would provide insights regarding the possibility of achieving them.</AbstractText>This study aimed to determine the population trends of cardiovascular disease risk factors in the National Capital Region of Delhi over 2 decades.</AbstractText>Two representative cross-sectional surveys were conducted among men and women ages 35 to 64 years, residing in the urban and rural areas (survey 1 [1991 to 1994] and survey 2 [2010 to 2012]) using similar methodology. The urban sample was collected from the Municipal Corporation of Delhi, and the rural sample was from the Ballabgarh block of the adjoining state of Haryana. A total of 3,048 and 2,052 subjects of urban areas and 2,487 and 1,917 subjects of rural areas were surveyed in surveys 1 and 2, respectively. Behavioral (smoking and alcohol use), physical (overweight, abdominal obesity, and raised blood pressure), and biochemical risk factors (raised fasting blood glucose and raised total cholesterol) were measured using standard tools.</AbstractText>Urban and rural prevalence of overweight, alcohol use, raised blood pressure, and blood glucose increased with increases in age-standardized mean body mass index (urban: 24.4 to 26.0 kg/m2</sup>; rural: 20.2 to 23.0 kg/m2</sup>), systolic blood pressure (urban: 121.2 to 129.8 mm Hg; rural: 114.9 to 123.1 mm Hg), diastolic blood pressure (urban: 74.3 to 83.9 mm Hg; rural: 73.1 to 82.3 mm Hg), and fasting glucose (urban: 101.2 to 115.3 mg/dl; rural: 83.9 to 103.2 mg/dl). The smoking prevalence increased in the rural male population. Raised total cholesterol declined in urban and increased significantly in rural populations.</AbstractText>The study indicates an overall worsening of population levels of all cardiovascular disease risk factors in National Capital Region over past 20 years, though some signs of stabilization and reversal are seen in urban Delhi.</AbstractText>Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
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2,335,275 |
An Interesting Case of Permanent His-Bundle Pacing and a Review of the Current Literature.
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Permanent His-bundle pacing (HBP) is a true physiological form of ventricular pacing that has been shown in recent years to be both safe and feasible in clinical practice. However, there are limited data about its long-term performance, especially when compared with both right ventricular and biventricular pacing. In this article, we present a thought-provoking case study that illustrates the usefulness of permanent HBP in a patient with long-standing complete infranodal heart block and progressive heart failure, and discuss the current literature highlighting the evidence behind this form of permanent pacing.
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2,335,276 |
Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia.
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A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), binds lipoprotein lipase and shuttles it to its site of action in the capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two plasma samples (both from patients with chylomicronemia) that contained an interfering substance that made it impossible to measure GPIHBP1. That finding raised the possibility that those samples might contain GPIHBP1 autoantibodies.</AbstractText>Using a combination of immunoassays, Western blot analyses, and immunocytochemical studies, we tested the two plasma samples (as well as samples from other patients with chylomicronemia) for the presence of GPIHBP1 autoantibodies. We also tested the ability of GPIHBP1 autoantibodies to block the binding of lipoprotein lipase to GPIHBP1.</AbstractText>We identified GPIHBP1 autoantibodies in six patients with chylomicronemia and found that these autoantibodies blocked the binding of lipoprotein lipase to GPIHBP1. As in patients with GPIHBP1 deficiency, those with GPIHBP1 autoantibodies had low plasma levels of lipoprotein lipase. Three of the six patients had systemic lupus erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had severe but transient chylomicronemia. Two of the patients with chylomicronemia and GPIHBP1 autoantibodies had a response to treatment with immunosuppressive agents.</AbstractText>In six patients with chylomicronemia, GPIHBP1 autoantibodies blocked the ability of GPIHBP1 to bind and transport lipoprotein lipase, thereby interfering with lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and causing severe hypertriglyceridemia. (Funded by the National Heart, Lung, and Blood Institute and the Leducq Foundation.).</AbstractText>
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2,335,277 |
Pacemaker Placement in Patients with Stroke-Mediated Autonomic Dysregulation.
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Lateral medullary syndrome (LMS) is an ischemic disease of the medulla oblongata, which involves the territory of the posterior inferior cerebellar artery. Lateral medullary syndrome is often missed as the cause of autonomic dysregulation in patients with recent brain stem stroke. Due to the location of the baroreceptor regulatory center in the lateral medulla oblongata, patients with LMS occasionally have autonomic dysregulation-associated clinical manifestations. We report a case of LMS-associated autonomic dysregulation. The case presented as sinus arrest and syncope, requiring permanent pacemaker placement. A dual-chamber pacemaker was placed, after failure of conservative measures to alleviate the patient's symptoms. Our case shows the importance of recognizing LMS as a potential cause for life-threatening arrhythmias, heart block, and symptomatic bradycardia. Placement of permanent pacemaker may be necessary in some patients with LMS presenting with syncope, secondary to sinus arrest.
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2,335,278 |
Red meat consumption and cardiovascular target organ damage (from the Strong Heart Study).
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The aim of this study was to investigate whether red meat consumption is related to changes in left ventricular mass (LVM), left atrial diameter and carotid atherosclerosis in American Indians.</AbstractText>We prospectively analyzed echocardiographic and carotid ultrasound data of 1090 adults aged 40 years and older enrolled in the Strong Heart Family Study who were free of cardiovascular disease at baseline - 535 (49%) were hypertensive and 555 (51%) participants were nonhypertensive. Processed and unprocessed red meat intake was ascertained by using a Block food-frequency questionnaire at baseline. Cardiac and vascular biomarkers were assessed at baseline and 4 years later. Marginal models with multivariate adjustment were used to assess the associations of red meat intake with LVM, left atrial diameter, intima-media thickness and presence and extent of carotid atherosclerosis.</AbstractText>Participants with hypertension were older, had a higher BMI, were more likely to be diabetic and less physically active. Processed and unprocessed red meat consumption was related to an increase in the presence of atherosclerotic plaques in male and female hypertensive individuals. In male hypertensive participants, processed meat intake was further observed to be associated with an increase in intima-media thickness, atrial diameter but not LVM. In nonhypertensive participants, neither unprocessed nor processed red meat intake was associated with changes in cardiac parameters or carotid atherosclerosis.</AbstractText>Over a 4-year period, red meat consumption was related to cardiovascular target organ damage in hypertensive American Indians. These findings emphasize the importance of dietary measures for cardiovascular disease prevention.</AbstractText>
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2,335,279 |
Early discrimination of sensorimotor Guillain-Barré syndrome into demyelinating or axonal subtype by automated nerve excitability testing.
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In the early stage of disease, differentiating acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor sensory axonal neuropathy (AMSAN) using only a conventional nerve conduction studies (NCS) may be difficult. We evaluated the differences in the motor axonal excitability properties of 16 cases of sensorimotor Guillain-Barré syndrome by nerve excitability testing (NET). The antiganglioside antibody assay and follow-up NCS resulted in 12 patients diagnosed as AIDP and 4 patients as AMSAN. Clinical and excitability parameters in each group were compared with those in 30 normal controls. Automated NET with threshold tracking techniques was used to calculate the strength-duration time constant (SDTC), threshold electrotonus (TE), current-threshold relationship (CTR), and recovery cycle (RC) of excitability. Except for subtle changes in excitability parameters, AIDP showed no definitive difference relative to normal controls. Comparison between AMSAN and normal controls also revealed no significant differences in the SDTC, TE, and CTR parameters. However, there were clear differences in some of the RC parameters: the relative refractory period was significantly longer in the AMSAN group than in the AIDP group (4.40 ± 1.11 vs. 3.09 ± 1.01 ms, mean ± SEM; p < 0.001), while superexcitability was significantly less prominent in the AMSAN group (-6.80 ± 10.30 vs. -26.48 ± 1.17%, mean ± SEM; p < 0.001). Our study identified that both AIDP and AMSAN were associated with subtle changes in excitability properties. Nonetheless, the prominent increase in refractoriness in AMSAN suggests the presence of a nodal conduction block.
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2,335,280 |
Supplementation with omega-3 acids after myocardial infarction and modification of inflammatory markers in light of the patients' diet: a preliminary study.
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Neuroendocrine activation, activation of proinflammatory cytokines and platelets, and endothelial dysfunction play a significant role in the development of heart failure (HF).</AbstractText>The aim of the work was to assess the effect of supplementation with EPA and DHA in a daily dose of 1 g on selected inflammatory markers and platelet activation in patients with HF after recent myocardial infarction in light of their diet.</AbstractText>This preliminary study was a randomised, double-blind trial involving 30 patients with post-infarction HF. One group received a product containing 1 g of omega-3 acids, while the other received placebo, i.e. corn oil 1 g daily for 12 weeks. At baseline and at week 12, venous blood was obtained in the fasted state in order to determine the following parameters: NT-proBNP, fibrinogen, INR, creatinine clearance, serum lipid profile, hsCRP, troponin, glucose, transaminases, GGTP, MCP-1, pentraxin 3, and CD-40. To evaluate the patient's diet and dietary intake of omega-3 acids, a 24-h dietary interview and the Block's Food Frequency Questionnaire (FFQ) were applied.</AbstractText>Supplementation of omega-3 acids in a dose of 1 g per day had no effect on lipid or inflammatory parameters, with the exception of pentraxin 3. In both groups, after three months of supplementation, overall consumption of energy and saturated fatty acids was significantly higher (p < 0.05).</AbstractText>Potential benefits associated with supplementation were nullified by a highly atherogenic diet. Apparently, supplementation of omega-3 acids without simultaneous dietary education and nutrition control does not bring the expected effect. Further research involving a larger group of patients is needed to better understand the relationship between patient's diet and the effectiveness of omega-3 supplementation.</AbstractText>
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2,335,281 |
Inclusion of biological knowledge in a Bayesian shrinkage model for joint estimation of SNP effects.
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With the aim of improving detection of novel single-nucleotide polymorphisms (SNPs) in genetic association studies, we propose a method of including prior biological information in a Bayesian shrinkage model that jointly estimates SNP effects. We assume that the SNP effects follow a normal distribution centered at zero with variance controlled by a shrinkage hyperparameter. We use biological information to define the amount of shrinkage applied on the SNP effects distribution, so that the effects of SNPs with more biological support are less shrunk toward zero, thus being more likely detected. The performance of the method was tested in a simulation study (1,000 datasets, 500 subjects with ∼200 SNPs in 10 linkage disequilibrium (LD) blocks) using a continuous and a binary outcome. It was further tested in an empirical example on body mass index (continuous) and overweight (binary) in a dataset of 1,829 subjects and 2,614 SNPs from 30 blocks. Biological knowledge was retrieved using the bioinformatics tool Dintor, which queried various databases. The joint Bayesian model with inclusion of prior information outperformed the standard analysis: in the simulation study, the mean ranking of the true LD block was 2.8 for the Bayesian model versus 3.6 for the standard analysis of individual SNPs; in the empirical example, the mean ranking of the six true blocks was 8.5 versus 9.3 in the standard analysis. These results suggest that our method is more powerful than the standard analysis. We expect its performance to improve further as more biological information about SNPs becomes available.
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2,335,282 |
Pharmacist participation in hospital ward teams and hospital readmission rates among people with dementia: a randomized controlled trial.
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To assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment.</AbstractText>This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years with dementia or cognitive impairment admitted to three wards at two hospitals located in Northern Sweden were included.</AbstractText>Of the 473 deemed eligible for participation, 230 were randomized to intervention and 230 to control group by block randomization. The primary outcome, risk of drug-related hospital readmissions, was assessed at 180 days of follow-up by intention-to-treat analysis. During the 180 days of follow-up, 18.9% (40/212) of patients in the intervention group and 23.0% (50/217) of those in the control group were readmitted for drug-related reasons (HR = 0.80, 95% CI = 0.53-1.21, p = 0.28, univariable Cox regression). Heart failure was significantly more common in the intervention group. After adjustment for heart failure as a potential confounder and an interaction term, multiple Cox regression analysis indicated that pharmacist participation significantly reduced the risk of drug-related readmissions (HR = 0.49, 95% CI = 0.27-0.90, p = 0.02). A post-hoc analysis showed a significantly reduced risk of 30-day readmissions due to drug-related problems in the total sample (without adjustment for heart failure).</AbstractText>Participation of clinical pharmacists in healthcare team conducting comprehensive medication reviews did not significantly reduce the risk of drug-related readmissions in patients with dementia or cognitive impairment; however, post-hoc and subgroup analyses indicated significant effects favoring the intervention. More research is needed.</AbstractText>Clinical trials NCT01504672.</AbstractText>
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2,335,283 |
Probe-Dependent Negative Allosteric Modulators of the Long-Chain Free Fatty Acid Receptor FFA4.
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High-affinity and selective antagonists that are able to block the actions of both endogenous and synthetic agonists of G protein-coupled receptors are integral to analysis of receptor function and to support suggestions of therapeutic potential. Although there is great interest in the potential of free fatty acid receptor 4 (FFA4) as a novel therapeutic target for the treatment of type II diabetes, the broad distribution pattern of this receptor suggests it may play a range of roles beyond glucose homeostasis in different cells and tissues. To date, a single molecule, 4-methyl-<i>N</i>-9<i>H</i>-xanthen-9-yl-benzenesulfonamide (AH-7614), has been described as an FFA4 antagonist; however, its mechanism of antagonism remains unknown. We synthesized AH-7614 and a chemical derivative and demonstrated these to be negative allosteric modulators (NAMs) of FFA4. Although these NAMs did inhibit FFA4 signaling induced by a range of endogenous and synthetic agonists, clear agonist probe dependence in the nature of allosteric modulation was apparent. Although AH-7614 did not antagonize the second long-chain free fatty acid receptor, free fatty acid receptor 1, the simple chemical structure of AH-7614 containing features found in many anticancer drugs suggests that a novel close chemical analog of AH-7614 devoid of FFA4 activity, 4-methyl-<i>N</i>-(9<i>H</i>-xanthen-9-yl)benzamide (TUG-1387), will also provide a useful control compound for future studies assessing FFA4 function. Using TUG-1387 alongside AH-7614, we show that endogenous activation of FFA4 expressed by murine C3H10T1/2 mesenchymal stem cells is required for induced differentiation of these cells toward a more mature, adipocyte-like phenotype.
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2,335,284 |
Comparison of Intravenous Dexmedetomidine with Midazolam in Prolonging Spinal Anaesthesia with Ropivacaine.
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Midazolam and dexmedetomidine both being sedatives, but the latter with additional analgesic properties is expected to prolong the duration of sensory and motor block obtained with spinal anaesthesia.</AbstractText>To compare intravenous dexmedetomidine with midazolam and placebo with respect to sensory and motor block duration, analgesia, and sedation in patients undergoing lower limb and lower abdominal surgeries with intrathecal ropivacaine anaesthesia.</AbstractText>In this single blind placebo controlled trial, 60 patients, classified as American Society of Anaesthesiologists' (ASA) physical status I-II, were randomized into three groups (n=20 per group). All patients were administered ropivacaine (15 mg) for spinal anaesthesia. Intravenous dexmedetomidine was administered in Group D (1 μg/kg loading dose over 10 minutes, followed by a continuous infusion (0.5 μg/kg/hr), intravenous midazolam was administered in Group M (0.05 mg/kg) loading dose, followed by a continuous infusion (0.02 mg/kg/hr) and normal saline was infused in Group C. Intraoperative haemodynamic changes, onset, level and duration of sensory block, onset and duration of motor block, level of sedation, postoperative analgesia and side effects were recorded.</AbstractText>Heart rate was seen to fall significantly in Group D patients for the first 15 minutes. Measurements of mean blood pressure revealed significant decrease in Group D after 40 minutes, whereas the fall in Group C occurred after 15 minutes. Duration of sensory block was significantly longer in Group D patients (208±19.358 mins) as compared to Group M and C where the duration was (177±15.252 mins) and (177±17.800 mins) respectively. Higher levels of sedation were achieved in Group D and M where sedation score was 3 (fully asleep but arousable), 90% cases in Group D and 100% cases in Group M. The time at which first analgesic was given to patients (VAS score 4) was (271.50±21.831) in Group D and (202±25.047) in M and (218.50±38.013) in Group C. Dexmedetomidine significantly prolongs duration of analgesia providing pain relief in intraoperative and postoperative period. Injection of diclofenac sodium 75 mg intramuscular was used as rescue analgesic. The VAS score reached a value of 4 earlier in the midazolam and saline group than dexmedetomidine group.</AbstractText>Intravenous dexmedetomidine prolonged spinal anaesthesia, though midazolam did not. It also provided sedation and additional analgesia. Therefore, dexmedetomidine is appropriate during spinal anaesthesia, although heart rate needs to be monitored cautiously.</AbstractText>
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2,335,285 |
Tbx18-dependent differentiation of brown adipose tissue-derived stem cells toward cardiac pacemaker cells.
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A cell-sourced biological pacemaker is a promising therapeutic approach for sick sinus syndrome (SSS) or severe atrial ventricular block (AVB). Adipose tissue-derived stem cells (ATSCs), which are optimal candidate cells for possible use in regenerative therapy for acute or chronic myocardial injury, have the potential to differentiate into spontaneous beating cardiomyocytes. However, the pacemaker characteristics of the beating cells need to be confirmed, and little is known about the underlying differential mechanism. In this study, we found that brown adipose tissue-derived stem cells (BATSCs) in mice could differentiate into spontaneous beating cells in 15% FBS Dulbecco's modified Eagle's medium (DMEM) without additional treatment. Subsequently, we provide additional evidence, including data regarding ultrastructure, protein expression, electrophysiology, and pharmacology, to support the differentiation of BATSCs into a cardiac pacemaker phenotype during the course of early cultivation. Furthermore, we found that silencing Tbx18, a key transcription factor in the development of pacemaker cells, terminated the differentiation of BATSCs into a pacemaker phenotype, suggesting that Tbx18 is required to direct BATSCs toward a cardiac pacemaker fate. The expression of Tbx3 and shox2, the other two important transcription factors in the development of pacemaker cells, was decreased by silencing Tbx18, which suggests that Tbx18 mediates the differentiation of BATSCs into a pacemaker phenotype via these two downstream transcription factors.
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2,335,286 |
Does the volume of supplemental intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized-double blind clinical trial.
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To investigate the efficacy of 0.2 mL vs. 0.6 mL of 2% lidocaine when given as a supplementary intraligamentary injection after a failed inferior alveolar nerve block (IANB).</AbstractText>Ninety-seven adult patients with symptomatic irreversible pulpits received an IANB and root canal treatment was initiated. Pain during treatment was recorded using a visual analogue scale (Heft-Parker VAS). Patients with unsuccessful anaesthesia (n = 78) randomly received intraligamentary injection of either 0.2 mL or 0.6 mL of 2% lidocaine with 1 : 80 000 epinephrine. Root canal treatment was reinitiated. Success after primary injection or supplementary injection was defined as no or mild pain (HP VAS score ≤54 mm) during access preparation and root canal instrumentation. Heart rate was monitored using a finger pulse oximeter. The anaesthetic success rates were analysed with Pearson chi-square test at 5% significance levels. The heart rate changes were analysed using t-tests.</AbstractText>The intraligamentary injections with 0.2 mL solution gave an anaesthetic success rate of 64%, whilst the 0.6 mL was successful in 84% of cases with failed primary IANB. (χ2</sup>  = 4.3, P = 0.03). There was no significant effect of the volume of intraligamentary injection on the change in heart rate.</AbstractText>Increasing the volume of intraligamentary injection improved the success rates after a failed primary anaesthetic injection.</AbstractText>© 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.</CopyrightInformation>
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2,335,287 |
Effect of an epinephrine mixture for interscalene block on hemodynamic changes after the beach chair position under general anesthesia: a retrospective study.
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The beach chair position (BCP) can cause significant hypotension. Epinephrine is used to prolong the duration of local anesthetics; it is also absorbed into blood and can exert systemic effects. This study determined the effects of epinephrine mixed with ropivacaine for an interscalene block (ISB) on hemodynamic changes related to BCP.</AbstractText>Patient data collected from March 2013 to August 2014 were used retrospectively. We divided the patients into three groups: 1) ISB only, 2) I+G (general anesthesia after ISB without epinephrine), and 3) I+E+G (general anesthesia after ISB with epinephrine). Mean blood pressure (MBP) and heart rate (HR) were measured for 30 minutes at 5-minute intervals.</AbstractText>The study analyzed data from 431 patients. MBP tended to decrease gradually in the groups I+G and I+E+G. There were significant differences in MBP between the groups I+G and I, and between the groups I+G and I+E+G. Group I+E+G showed a significant increase in HR compared with the other two groups.</AbstractText>ISB with an epinephrine mixture did not prevent hypotension caused by the BCP after general anesthesia. HR increased only in response to the epinephrine mixture. A well-planned prospective study is required to compare hemodynamic changes in that context.</AbstractText>
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2,335,288 |
MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care.
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Detection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital.</AbstractText>A decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care.</AbstractText>Data from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective.</AbstractText>The current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4400 per quality adjusted life year (QALY) gained compared to a "do nothing" strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥400pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses.</AbstractText>This represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.</AbstractText>Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
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2,335,289 |
Mitochondrial Cx43 hemichannels contribute to mitochondrial calcium entry and cell death in the heart.
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Mitochondrial connexin 43 (Cx43) plays a key role in cardiac cytoprotection caused by repeated exposure to short periods of non-lethal ischemia/reperfusion, a condition known as ischemic preconditioning. Cx43 also forms calcium (Ca<sup>2+</sup>)-permeable hemichannels that may potentially lead to mitochondrial Ca<sup>2+</sup> overload and cell death. Here, we studied the role of Cx43 in facilitating mitochondrial Ca<sup>2+</sup> entry and investigated its downstream consequences. To that purpose, we used various connexin-targeting peptides interacting with extracellular (Gap26) and intracellular (Gap19, RRNYRRNY) Cx43 domains, and tested their effect on mitochondrial dye- and Ca<sup>2+</sup>-uptake, electrophysiological properties of plasmalemmal and mitochondrial Cx43 channels, and cell injury/cell death. Our results in isolated mice cardiac subsarcolemmal mitochondria indicate that Cx43 forms hemichannels that contribute to Ca<sup>2+</sup> entry and may trigger permeability transition and cell injury/death. RRNYRRNY displayed the strongest effects in all assays and inhibited plasma membrane as well as mitochondrial Cx43 hemichannels. RRNYRRNY also strongly reduced the infarct size in ex vivo cardiac ischemia-reperfusion studies. These results indicate that Cx43 contributes to mitochondrial Ca<sup>2+</sup> homeostasis and is involved in triggering cell injury/death pathways that can be inhibited by RRNYRRNY peptide.
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2,335,290 |
GSTM1 polymorphism in patients with clinical manifestations of atherosclerosis.
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Atherosclerosis is characterized by lesions, called atheroma or atheromatous plaques, in the inner layer of blood vessels, which block the vascular lumen and weaken the underlying tunica media. Several modifiable and non-modifiable risk factors for the development of atherosclerosis exist. The modifiable risk factors include hypertension, smoking, obesity, high LDL and low HDL cholesterol levels, sedentary lifestyle, and stress; the non-modifiable factors include diabetes mellitus, family history of hypertension and heart disease, thrombophilia, sex, age, and genetic factors. The association of polymorphisms in GST with coronary artery disease has been studied since the polymorphisms can affect enzyme activity and contribute to the onset of atherosclerosis. We analyzed polymorphisms in GSTM1 in individuals diagnosed with atherosclerosis as well as in healthy individuals (control group). The frequency of the GSTM1 present genotype in the atherosclerosis group was 1.2 times higher than that observed in the control group. We found no sex- or alcohol-consumption-dependent differences between the occurrences of the present and null genotypes. However, the GSTM1 present genotype occurred in 52.6% individuals with atherosclerosis who reported smoking 20 or more cigarettes per day and in 60% individuals who smoked 10 to 20 cigarettes per day (P = 0.0035). In addition, the GSTM1 present genotype was more frequent in individuals who reported being former smokers - 45.5% in individuals with atherosclerosis who smoked for more than 20 years and 50% each for individuals in the control group who smoked for less than 10 years or for 10 to 20 years, respectively (P = 0.0240).
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2,335,291 |
Vestibular Activation Habituates the Vasovagal Response in the Rat.
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Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long-Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20-50 mmHg and ≈20-50 beats/min (bpm) into a vasovagal response when stimulated with Sgv\S in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low-frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when vasovagal responses are induced. Habituation also produced significant increases in baroreflex sensitivity (<i>p</i> < 0.001). Thus, repeated low-frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of vasovagal responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low-frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of vasovagal responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of vasovagal syncope in humans.
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2,335,292 |
Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension.
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Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression. RAP poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) NPs were fabricated. NP accumulation and efficacy were examined in a rat monocrotaline model of PAH. Following intravenous (IV) administration, NP accumulation in diseased lungs was verified via LC/MS analysis and confocal imaging. Pulmonary arteriole thickness, right ventricular systolic pressures, and ventricular remodeling were determined to assess the therapeutic potential of RAP NPs. Monocrotaline-exposed rats showed increased NP accumulation within lungs compared to healthy controls, with NPs present to a high extent within pulmonary perivascular regions. RAP, in both free and NP form, attenuated PAH development, with histological analysis revealing minimal changes in pulmonary arteriole thickness and no ventricular remodeling. Importantly, NP-treated rats showed reduced systemic side effects compared to free RAP. This study demonstrates the potential for nanoparticles to significantly impact PAH through site-specific delivery of therapeutics.
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2,335,293 |
Quantifying the foodscape: A systematic review and meta-analysis of the validity of commercially available business data.
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This paper reviews studies of the validity of commercially available business (CAB) data on food establishments ("the foodscape"), offering a meta-analysis of characteristics associated with CAB quality and a case study evaluating the performance of commonly-used validity indicators describing the foodscape. Existing validation studies report a broad range in CAB data quality, although most studies conclude that CAB quality is "moderate" to "substantial". We conclude that current studies may underestimate the quality of CAB data. We recommend that future validation studies use density-adjusted and exposure measures to offer a more meaningful characterization of the relationship of data error with spatial exposure.
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2,335,294 |
Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia.
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Functional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD.</AbstractText>Ten-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the "stomach" point with different parameters or sham-EA was performed on 8-week-old animals. Gastric sensitivity to gastric distention was measured under different conditions. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. Naloxone was injected intraperitoneally before AEA to explore the opioid mechanism. Gastric emptying was measured at the end of the study.</AbstractText>1) Gastric sensitivity to gastric distention was higher in the FD rats. AEA with parameters of 0.1s on, 0.4s off, 100Hz, 0.3ms and 0.4-0.5mA, but not other parameters or sham-EA, decreased gastric hypersensitivity in the FD rats. Naloxone did not block the effect of AEA. 2) Lower vagal activity and higher sympathovagal ratio were noted in the FD rats, compared with the controls. AEA increased vagal activity and improved sympathovagal imbalance.</AbstractText>AEA ameliorates gastric hypersensitivity in FD rats and this effect may be attributed to the improvement of sympathovagal balance.</AbstractText>
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2,335,295 |
Finite element analysis of implant-supported prosthesis with pontic and cantilever in the posterior maxilla.
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The aim of this study was to evaluate the influence of pontic and cantilever designs (mesial and distal) on 3-unit implant-retained prosthesis at maxillary posterior region verifying stress and strain distributions on bone tissue (cortical and trabecular bones) and stress distribution in abutments, implants and fixation screws, under axial and oblique loadings, by 3D finite element analysis. Each model was composed of a bone block presenting right first premolar to the first molar, with three or two external hexagon implants (4.0 × 10 mm), supporting a 3-unit splinted dental fixed dental prosthesis with the variations: M1 - three implants supporting splinted crowns; M2 - two implants supporting prosthesis with central pontic; M3 - two implants supporting prosthesis with mesial cantilever; M4 - two implants supporting prosthesis with distal cantilever. The applied forces were 400 N axial and 200 N oblique. The von Mises criteria was used to evaluate abutments, implants and fixation screws and maximum principal stress and microstrain criteria were used to evaluate the bone tissue. The decrease of the number of implants caused an unfavorable biomechanical behavior for all structures (M2, M3, M4). For two implant-supported prostheses, the use of the central pontic (M2) showed stress and strain distributions more favorable in the analyzed structures. The use of cantilever showed unfavorable biomechanical behavior (M3 and M4), mainly for distal cantilever (M4). The use of three implants presented lower values of stress and strain on the analyzed structures. Among two implant-supported prostheses, prostheses with cantilever showed unfavorable biomechanical behavior in the analyzed structures, especially for distal cantilever.
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2,335,296 |
Electrocardiographic abnormalities in treatment-naïve HIV subjects in south-east Nigeria.
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Cardiac complications of human immunodeficiency virus (HIV) infection are important causes of morbidity and mortality. We set out to determine the electrocardiographic (ECG) abnormalities in treatment-naïve HIV-positive patients in Enugu, south-east Nigeria.</AbstractText>This was a cross-sectional study involving 250 HIV-positive and 200 HIV-negative subjects. Demographic and anthropometric data, relevant investigations and ECG results were compared between the groups.</AbstractText>An abnormal ECG was present in 70% of the HIV-positive patients, sinus bradycardia in 64%, QTC prolongation in 48%, T-wave inversion in 21.6%, Wolf-Parkinson-White syndrome in 0.8%, abnormal P waves in 12.8%, 1st</sup> degree heart block in 2.4%, ST depression in 30%, and left-axis deviation in 1.6%. Underweight was associated with ECG abnormalities (p = 0.001). The HIV-positive patients had more ECG abnormalities than the HIV-negative subjects (p = 0.001).</AbstractText>Electrocardiographic abnormalities were common in treatment-naïve HIV-positive patients in Enugu, Nigeria. The 70% prevalence of ECG abnormalities in treatment-naïve HIV-positive patients was high. There is a need to evaluate HIV-positive patients at onset for cardiac and non-cardiac abnormalities detectable by ECG.</AbstractText>
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2,335,297 |
β-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α-PP2A-Mediated Dephosphorylation.
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Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5. The relative importance of phosphorylation at Ser259/Ser498 versus Ser279 in HDAC5 regulation is also controversial. We aimed to determine the impact of β-AR stimulation on the phosphorylation, localization, and function of cardiomyocyte HDAC5 and delineate underlying molecular mechanisms.</AbstractText>A novel 3-dimensional confocal microscopy method that objectively quantifies the whole-cell nuclear/cytoplasmic distribution of green fluorescent protein tagged HDAC5 revealed the β-AR agonist isoproterenol to induce β1</sub>-AR-mediated and protein kinase A-dependent HDAC5 nuclear accumulation in adult rat cardiomyocytes, which was accompanied by dephosphorylation at Ser259/279/498. Mutation of Ser259/Ser498 to Ala promoted HDAC5 nuclear accumulation and myocyte enhancer factor-2 inhibition, whereas Ser279 ablation had no such effect and did not block isoproterenol-induced nuclear accumulation. Inhibition of the Ser/Thr phosphatase PP2A blocked isoproterenol-induced HDAC5 dephosphorylation. Co-immunoprecipitation revealed a specific interaction of HDAC5 with the PP2A targeting subunit B55α, as well as catalytic and scaffolding subunits, which increased >3-fold with isoproterenol. Knockdown of B55α in neonatal cardiomyocytes attenuated isoproterenol-induced HDAC5 dephosphorylation.</AbstractText>β-AR stimulation induces HDAC5 nuclear accumulation in cardiomyocytes by a mechanism that is protein kinase A-dependent but requires B55α-PP2A-mediated dephosphorylation of Ser259/Ser498 rather than protein kinase A-mediated phosphorylation of Ser279.</AbstractText>© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.</CopyrightInformation>
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2,335,298 |
Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial.
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Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes.</AbstractText>In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks' gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152.</AbstractText>Between Jan 6, 2010, and Aug 31, 2013, 47 062 women were randomly assigned (23 515 in the decision-support group and 23 547 in the no-decision-support group) and 46 042 were analysed (22 987 in the decision-support group and 23 055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups-172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82-1·25). At 2 years, no significant differences were noted in terms of developmental assessment.</AbstractText>Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal monitoring in labour does not improve clinical outcomes for mothers or babies.</AbstractText>National Institute for Health Research.</AbstractText>Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
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2,335,299 |
Characterization and consistency of interactions of triggers and substrate at the onset of paroxysmal atrial fibrillation.
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Initiating mechanisms of atrial fibrillation (AF) remain poorly understood, involving complex interaction between triggers and the atrial substrate. This study sought to classify the transitional phenomena, hypothesizing that there is consistency within and between patients in trigger-substrate interaction during transition to AF.</AbstractText>Non-contact left atrial (LA) mapping was performed in 17 patients undergoing ablation for paroxysmal AF. All had spontaneous ectopy. Left atrial activation from the first ectopic to established AF was examined offline to characterize the initiating and transitional sequence of activation. In 57 fully mapped spontaneous AF initiations in 8 patients, all involved interaction of pulmonary venous/LA triggers with a septopulmonary line of block (SP-LOB) also evident in sinus rhythm, by 4 different transitional mechanisms characterized by (i) continuous focal firing: AF resulted from fragmentation of each ectopic wavefront through gaps in the SP-LOB and persisted only while focal firing continued (n = 18/32%) (ii) transient focal firing, wavefront fragmentation at the SP-LOB produced wavelet re-entry that persisted after cessation of an initiating ectopic source (n = 12/21%), (iii) of two separate interacting ectopic foci (n = 15/26%), or from (iv) transiently stable macroreentry (n = 12/21%), around the SP-LOB extending to the LA roof, resulting in progressive wavefront fragmentation. It was found that 79 ± 22% of each of the initiations in individual patients showed the same triggering mechanism.</AbstractText>Onset of paroxysmal AF can be described by discrete mechanistic categories, all involving interaction of ectopic activity with a common SP-LOB. Within/between-patient consistency of initiations suggests constancy of the interacting triggers and substrate, and supports the concept of mechanistically tailored treatment.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: [email protected].</CopyrightInformation>
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