Checking out the Complementarity of Pancreatic Ductal Adenocarcinoma Preclinical Designs

48, 0.97] and very-high 0.69 [0.52, 0.91]), CV death (0.75 [0.48, 1.18] and 0.56 [0.41, 0.78]), HHF (0.53 [0.28, 1.01] and 0.67 [0.48, 0.96]), and CV death or HHF (0.69 [0.46, 1.03]) and (0.64 [0.49, 0.82]) across all risk categories versus placebo. Higher absolute risk reductions (ARRs) were observed for CV death in the very-high versus low-intermediate category (P = 0.01). CONCLUSIONS Applied to EMPA-REG OUTCOME, higher TRS-HFDM was associated with increased HHF and mortality risk. Empagliflozin reduced CV outcomes across TRS-HFDM categories. ABT-199 Higher ARRs were associated with higher risk scores. © 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.OBJECTIVE Pathological skin picking (PSP) is characterized by repetitive scratching, biting, and picking of the skin. The disorder is subsumed under the section "obsessive-compulsive and related disorders" in the DSM-5. A related body-focused repetitive disorder, which has received less empirical attention so far, is dermatophagia or dermatodaxia (eating or biting/gnawing of the skin). Habit reversal training (HRT) is regarded as the treatment of choice demonstrating improvement at a medium effect size relative to control conditions. METHODS The present case report describes a 50-year-old man with a lifetime history of PSP and dermatodaxia of the fingertips who stopped excessive nail-biting approximately 10 years ago using a treatment method known as decoupling. Yet, his PSP and dermatodaxia remained treatment-refractory after treatment with both decoupling (conventional protocol) and HRT. RESULTS Using a revised protocol of decoupling, the man was able to fully stop PSP and dermatodaxia; only the tendency to fidget nervously with his hands remained. The case report describes the revised protocol. Scores on the Skin Picking Scale Revised (SPS-R) dropped from 15 to 0. DISCUSSION The revised decoupling protocol is an easy to use technique that holds promise in this underdiagnosed and undertreated condition. Yet, rigorous randomized controlled studies are needed to ascertain its efficacy. © 2020 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals, Inc.Depolarisation-secretion coupling is assumed to be dependent only on extracellular calcium ([Ca2+ ]o ). Ryanodine receptor (RyR)-sensitive stores in hypothalamic neurohypophysial system (HNS) terminals produce sparks of intracellular calcium ([Ca2+ ]i ) that are voltage-dependent. We hypothesised that voltage-elicited increases in intraterminal calcium are crucial for neuropeptide secretion from presynaptic terminals, whether from influx through voltage-gated calcium channels and/or from such voltage-sensitive ryanodine-mediated calcium stores. Increases in [Ca2+ ]i upon depolarisation in the presence of voltage-gated calcium channel blockers, or in the absence of [Ca2+ ]o , still give rise to neuropeptide secretion from HNS terminals. Even in 0 [Ca2+ ]o , there was nonetheless an increase in capacitance suggesting exocytosis upon depolarisation. This was blocked by antagonist concentrations of ryanodine, as was peptide secretion elicited by high K+ in 0 [Ca2+ ]o . Furthermore, such depolarisations lead to increases in [Ca2+ ]i . Pre-incubation with BAPTA-AM resulted in > 50% inhibition of peptide secretion elicited by high K+ in 0 [Ca2+ ]o . Nifedipine but not nicardipine inhibited both the high K+ response for neuropeptide secretion and intraterminal calcium, suggesting the involvement of CaV1.1 type channels as sensors in voltage-induced calcium release. Importantly, RyR antagonists also modulate neuropeptide release under normal physiological conditions. In conclusion, our results indicate that depolarisation-induced neuropeptide secretion is present in the absence of external calcium, and calcium release from ryanodine-sensitive internal stores is a significant physiological contributor to neuropeptide secretion from HNS terminals. © 2020 British Society for Neuroendocrinology.OBJECTIVES Preclinical studies have shown that surgically implanted vagus nerve stimulation (VNS) promotes recovery of consciousness and cognitive function following experimental traumatic brain injury (TBI). The aim of this study is to report the feasibility and safety of a noninvasive transcutaneous vagus nerve stimulation (tVNS) in patients with persistent impairment of consciousness following severe TBI. MATERIALS AND METHODS The feasibility of tVNS was evaluated in five patients presenting with diffuse axonal injury and reduced dominant EEG activity one month following severe TBI. tVNS was applied to the left cymba conchae of the external ear using a skin electrode four hours daily for eight weeks. Possible effects of tVNS on physiological parameters and general side effects were recorded. In addition, we report the rate of recovery using coma recovery scale revised (CRS-R). RESULTS The tVNS regime of four hours daily for eight weeks was feasible and well tolerated with little side effects and no clinically relevant effects on physiological parameters. Three patients showed improvements (>3 points) in the CRS-R following eight weeks tVNS. CONCLUSION We demonstrated that tVNS is a feasible and safe VNS strategy for patients following severe TBI. Controlled studies are needed to clarify whether tVNS has a potential to promote recovery of consciousness following severe TBI. © 2020 International Neuromodulation Society.Perturbing the electronic structure of MoS2 basal plane via confining heteroatoms offers the opportunity to trigger in-plane activity for hydrogen evolution reaction (HER). The key challenge consists in inducing the optimum HER activity by controlling the type and distribution of confined atoms. Herein, we report a distance synergy of MoS2-confined single-atom rhodium realizing an ultra-high HER activity at the in-plane S sites adjacent to the rhodium. By optimizing the distance between the confined Rh atoms, an ultra-low overpotential of 67 mV is achieved at a current density of 10 mA cm-2 in acidic solution. Experiments and first-principles calculations demonstrate a unique distance synergy between the confined rhodium atoms in tuning the reactivity of neighbouring in-plane S atoms, which presents a volcanic trend with the inter-rhodium distance. This study provides a new strategy to tailor the activity of MoS2 surface via modulating the distance between confined single atoms. © 2020 WILEY-VCH Verlag GmbH & Co.