Dynamic clamp with StdpC software

Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording

Predictors of injury mortality: Findings from a large national cohort in Thailand

Objective: To present predictors of injury mortality by types of injury and by pre-existing attributes or other individual exposures identified at baseline

Re-Evaluation of the Action Potential Upstroke Velocity as a Measure of the Na+ Current in Cardiac Myocytes at Physiological Conditions

Background: The SCN5A encoded sodium current (INa) generates the action potential (AP) upstroke and is a major determinant of AP characteristics and AP propagation in cardiac myocytes. Unfortunately, in cardiac myocytes, investigation of kinetic properties of INa with near-physiological ion concentrations and temperature is technically challenging due to the large amplitude and rapidly activating nature of INa, which may seriously hamper the quality of voltage control over the membrane. We hypothesized that the alternating voltage clamp-current clamp (VC/CC) technique might provide an alternative to traditional voltage clamp (VC) technique for the determination of INa properties under physiological conditions. Principal Findings: We studied INa under close-to-physiological conditions by VC technique in SCN5A cDNA-transfected HEK cells or by alternating VC/CC technique in both SCN5A cDNA-transfected HEK cells and rabbit left ventricular myocytes. In these experiments, peak INa during a depolarizing VC step or maximal upstroke velocity, dV/dtmax, during VC/CC served as an indicator of available INa. In HEK cells, biophysical properties of INa, including current density, voltage dependent (in)activation, development of inactivation, and recovery from inactivation, were highly similar in VC and VC/CC experiments. As an application of the VC/CC technique we studied INa in left ventricular myocytes isolated from control or failing rabbit hearts

Long-term air pollution exposure and self-reported morbidity: A longitudinal analysis from the Thai cohort study (TCS)

[Background] Several studies have shown the health effects of air pollutants, especially in China, North American and Western European countries. But longitudinal cohort studies focused on health effects of long-term air pollution exposure are still limited in Southeast Asian countries where sources of air pollution, weather conditions, and demographic characteristics are different. The present study examined the association between long-term exposure to air pollution and self-reported morbidities in participants of the Thai cohort study (TCS) in Bangkok metropolitan region (BMR), Thailand. [Methods] This longitudinal cohort study was conducted for 9 years from 2005 to 2013. Self-reported morbidities in this study included high blood pressure, high blood cholesterol, and diabetes. Air pollution data were obtained from the Thai government Pollution Control Department (PCD). Particles with diameters ≤10 μm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), ozone (O₃), and carbon monoxide (CO) exposures were estimated with ordinary kriging method using 22 background and 7 traffic monitoring stations in BMR during 2005–2013. Long-term exposure periods to air pollution for each subject was averaged as the same period of person-time. Cox proportional hazards models were used to examine the association between long-term air pollution exposure with self-reported high blood pressure, high blood cholesterol, diabetes. Results of self-reported morbidity were presented as hazard ratios (HRs) per interquartile range (IQR) increase in PM₁₀, O₃, NO₂, SO₂, and CO. [Results] After controlling for potential confounders, we found that an IQR increase in PM₁₀ was significantly associated with self-reported high blood pressure (HR = 1.13, 95% CI: 1.04, 1.23) and high blood cholesterol (HR = 1.07, 95%CI: 1.02, 1.12), but not with diabetes (HR = 1.05, 95%CI: 0.91, 1.21). SO₂ was also positively associated with self-reported high blood pressure (HR = 1.22, 95%CI: 1.08, 1.38), high blood cholesterol (HR = 1.20, 95%CI: 1.11, 1.30), and diabetes (HR = 1.21, 95%CI: 0.92, 1.60). Moreover, we observed a positive association between CO and self-reported high blood pressure (HR = 1.07, 95%CI: 1.00, 1.15), but not for other diseases. However, self-reported morbidities were not associated with O₃ and NO₂. [Conclusions] Long-term exposure to air pollution, especially for PM₁₀ and SO₂ was associated with self-reported high blood pressure, high blood cholesterol, and diabetes in subjects of TCS. Our study supports that exposure to air pollution increases cardiovascular disease risk factors for younger population

Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes

Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.Peer reviewe

General practitioners knowledge and management of whiplash associated disorders and post-traumatic stress disorder: Implications for patient care

© 2016 The Author(s). Background: In Australia, general practitioners (GPs) see around two-thirds of people injured in road traffic crashes. Road traffic crash injuries are commonly associated with diverse physical and psychological symptoms that may be difficult to diagnose and manage. Clinical guidelines have been developed to assist in delivering quality, consistent care, however the extent to which GPs knowledge and practice in diagnosing and managing road traffic crash injuries concords with the guidelines is unknown. This study aimed to explore Australian GPs knowledge, attitudes and practices regarding the diagnosis and management of road traffic crash injuries, specifically whiplash associated disorders (WAD) and post-traumatic stress disorder (PTSD). Method: A cross-sectional survey of 423 GPs across Australia conducted between July and December 2014. We developed a questionnaire to assess their knowledge of WAD and PTSD, confidence in diagnosing and managing WAD and PTSD, frequency of referral to health providers, barriers to referral, and attitudes towards further education and training. Factor analysis, Spearman's correlation, and multiple ordered logistic regressions were performed. Results: Overall, GPs have good level knowledge of WAD and PTSD; only 9.6 % (95 % CI: 7.1 %, 12.8 %) and 23.9 % (95 % CI: 20.8 %, 28.2 %) of them were deemed to have lower level knowledge of WAD and PTSD respectively. Key knowledge gaps included imaging indicators for WAD and indicators for psychological referral for PTSD. GPs who were male, with more years of experience, working in the urban area and with higher knowledge level of WAD were more confident in diagnosing and managing WAD. Only GPs PTSD knowledge level predicted confidence in diagnosing and managing PTSD. GPs most commonly referred to physiotherapists and least commonly to vocational rehabilitation providers. Barriers to referral included out-of-pocket costs incurred by patients and long waiting times. Most GPs felt positive towards further education on road traffic crash injury management. Conclusion: This study has enhanced understanding of the knowledge skills and attitudes of GPs towards road traffic crash injury care in Australia, and has identified areas for further education and training. If delivered, this training has the potential to reduce unnecessary imaging for WAD and optimise the early referral of patients at risk of delayed recovery following a road traffic crash

Netherlands

The Netherlands traditionally had ample early retirement possibilities. Several reforms introduced from the late 1990s onward contributed to the successful reversal of this early exit trend. As a result, in 2018, employees o

Predictors of injury mortality : findings from a large national cohort in Thailand

Objective: To present predictors of injury mortality by types of injury and by pre-existing attributes or other individual exposures identified at baseline. Design: 5-year prospective longitudinal study. Setting: Contemporary Thailand (2005-2010), a country undergoing epidemiological transition. Participants: Data derived from a research cohort of 87 037 distance-learning students enrolled at Sukhothai Thammathirat Open University residing nationwide. Measures: Cohort members completed a comprehensive baseline mail-out questionnaire in 2005 reporting geodemographic, behavioural, health and injury data. These responses were matched with national death records using the Thai Citizen ID number. Age-sex adjusted multinomial logistic regression was used to calculate ORs linking exposure variables collected at baseline to injury deaths over the next 5 years. Results: Statistically significant predictors of injury mortality were being male (adjustedOR 3.87, 95% CI 2.39 to 6.26), residing in the southern areas (AOR 1.71, 95% CI 1.05 to 2.79), being a current smoker (1.56, 95% CI 1.03 to 2.37), history of drunk driving (AOR 1.49, 95% CI 1.01 to 2.20) and ever having been diagnosed for depression (AOR 1.91, 95% CI 1.00 to 3.69). Other covariates such as being young, having low social support and reporting road injury in the past year at baseline had moderately predictive AORs ranging from 1.4 to 1.6 but were not statistically significant. Conclusions: We complemented national death registration with longitudinal data on individual, social and health attributes. This information is invaluable in yielding insight into certain risk traits such as being a young male, history of drunk driving and history of depression. Such information could be used to inform injury prevention policies and strategies