The role of gap junctions in inflammatory and neoplastic disorders (Review).

Gap junctions are intercellular channels made of connexin proteins, mediating both electrical and biochemical signals between cells. The ability of gap junction proteins to regulate immune responses, cell proliferation, migration, apoptosis and carcinogenesis makes them attractive therapeutic targets for treating inflammatory and neoplastic disorders in different organ systems. Alterations in gap junction profile and expression levels are observed in hyperproliferative skin disorders, lymphatic vessel diseases, inflammatory lung diseases, liver injury and neoplastic disorders. It is now recognized that the therapeutic effects mediated by traditional pharmacological agents are dependent upon gap junction communication and may even act by influencing gap junction expression or function. Novel strategies for modulating the function or expression of connexins, such as the use of synthetic mimetic peptides and siRNA technology are considered.Dr Gary Tse received a BBSRC Doctoral Training Award at the University of Cambridge and is grateful to the Croucher Foundation for its support of his non‑clinical and clinical assistant professorships. Dr Yin Wah Fiona Chan was supported by the ESRC for her research at the University of Cambridge

Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies.

This is the final version of the article. It first appeared from Frontiers via https://doi.org/10.3389/fphys.2016.00467Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na+ channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na+, K+, Ca2+, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.GT received a BBSRC Doctoral CASE Studentship at the University of Cambridge and thanks the Croucher Foundation of Hong Kong for the support of his Clinical Assistant Professorship. YC is supported by the ESRC for her Ph.D. studies at the University of Cambridge. BY received funding from the Research Grant Council of Hong Kong for his research

Comparing distribution of harbour porpoise using Generalized Additive Models and hierarchical Bayesian models with Integrated Nested Laplace Approximation

Open Access via Elsevier agreement Acknowledgments We thank colleagues at the University of Aberdeen, Moray First Marine, NERI, Hi-Def Aerial Surveying Ltd and Ravenair for essential support in the field, particularly Tim Barton, Bill Ruck, Rasmus Nielson and Dave Rutter. L.D.W. was supported by the Marine Alliance for Science and Technology for Scotland (MASTS), the University of Aberdeen and Marine Scotland Science. Collaboration between the University of Aberdeen and Marine Scotland was supported by the Marine Collaboration Research Forum (MarCRF). Digital aerial surveys in 2010 were funded by Moray Offshore Renewables Ltd and 2014 by Marine Scotland. Additional funding for analysis of the combined datasets was provided by Marine Scotland. Collaboration between the University of Aberdeen and Marine Scotland was supported by MarCRF.Peer reviewedPublisher PD

Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC

Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC

5S solutions to promote medication efficiency and safety. Comment on Br J Anaesth 2023; 130: e416–8

We recently tested the impact of colour-coded compartmentalised syringe trays on drug error detection in 40 volunteers and found improved visual search efficacy compared with conventional drug handling trays. 2 Although not acknowledged in our paper, the use of colour-coded compartmentalised trays addresses four of the five ‘S's’ described by Moore and Webster-Edge: sort, straighten, shine, and standardise. We believe the data generated by our work demonstrate the collective impact of these four processes on task performance in a laboratory setting

Standardised colour-coded compartmentalised syringe trays improve anaesthetic medication visual search and mitigate cognitive load

Anaesthetic procedures are complex and subject to human error. Interventions to alleviate medication errors include organised syringe storage trays, but no standardised methods for drug storage have yet been widely implemented. We used experimental psychology methods to explore the potential benefits of colour-coded compartmentalised trays compared with conventional trays in a visual search task. We hypothesised that colour-coded compartmentalised trays would reduce search time and improve error detection for both behavioural and eye-movement responses. We recruited 40 volunteers to identify syringe errors presented in pre-loaded trays for 16 trials in total: 12 error present and four error absent, with eight trials presented for each tray type. Errors were detected faster when presented in the colour-coded compartmentalised trays than in conventional trays (11.1 s vs 13.0 s, respectively; P=0.026). This finding was replicated for correct responses for error-absent trays (13.3 s vs 17.4 s, respectively; P=0.001) and in the verification time of error-absent trays (13.1 s vs 17.2 s, respectively; P=0.001). On error trials, eye-tracking measures revealed more fixations on the drug error for colour-coded compartmentalised trays (5.3 vs 4.3, respectively; P<0.001), whilst more fixations on the drug lists for conventional trays (8.3 vs 7.1, respectively; P=0.010). On error-absent trials, participants spent longer fixating on the conventional trials (7.2 s vs 5.6 s, respectively; P=0.002). Colour-coded compartmentalisation enhanced visual search efficacy of pre-loaded trays. Reduced fixations and fixation times for the loaded tray were shown for colour-coded compartmentalised trays, indicating a reduction in cognitive load. Overall, colour-coded compartmentalised trays were associated with significant performance improvements when compared with conventional trays

The role of connexins in wound healing and repair: novel therapeutic approaches

Gap junctions are intercellular proteins responsible for mediating both electrical and biochemical coupling through the exchange of ions, second messengers and small metabolites. They are made of two connexons, with each (one) connexon supplied by each cell. A connexon consists of a hexamer of connexins with m. More than 20 connexin isoforms have been described in the literature thus far. Connexins have a short half-life, and therefore gap junction remodelling constantly occurs with a high turnover rate. Connexins undergo post-translational modification, such as phosphorylation, which can modify their channel activities. In this article, the roles of connexins in wound healing and repair are explored. We also consider nNovel strategies for modulating the function or expression of connexins, such as the use of antisense technology, synthetic mimetic peptides and bioactive materials, for the treatment of skin wounds, diabetic and pressure ulcers as well as cornea wounds. are considered

Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies

Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na + channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na + , K + , Ca 2+ , and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved-or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers

Table_1_Atrial Fibrillation Recurrence and Peri-Procedural Complication Rates in nMARQ vs. Conventional Ablation Techniques: A Systematic Review and Meta-Analysis.docx

<p>Background and Objectives: Atrial fibrillation is a common abnormal cardiac rhythm caused by disorganized electrical impulses. AF which is refractory to antiarrhythmic management is often treated with catheter ablation. Recently a novel ablation system (nMARQ) was introduced for PV isolation. However, there has not been a systematic review of its efficacy or safety compared to traditional ablation techniques. Therefore, we conducted this meta-analysis on the nMARQ ablation system.</p><p>Methods: PubMed and EMBASE were searched up until 1st of September 2017 for articles on nMARQ. A total of 136 studies were found, and after screening, 12 studies were included in this meta-analysis.</p><p>Results: Our meta-analysis shows that the use of nMARQ was associated with higher odds of AF non-recurrence (n = 1123, odds ratio = 6.79, 95% confidence interval 4.01–11.50; P < 0.05; I² took a value of 83%). Moreover, the recurrence rate of AF using nMARQ was not significantly different from that of traditional ablation procedures (n = 158 vs. 196; OR = 0.97, 95% confidence interval:0.59–1.61). No significant difference in complication rates was observed between these groups (RR: 0.86; 95% CI: 0.37–1.99; P > 0.05). There were four reported mortalities in the nMARQ group compared to none in the conventional ablation group (relative risk: 1.58; 95% CI: 0.09–29.24; P > 0.05).</p><p>Conclusions: AF recurrence rates are comparable between nMARQ and conventional ablation techniques. Although general complication rates are similar for both groups, the higher mortality with nMARQ suggests that conventional techniques should be used for resistant AF until improved safety profiles of nMARQ can be demonstrated.</p