Dual depolarization responses generated within the same lateral septal neurons by TRPC4-containing channels

In the central nervous system, canonical transient receptor potential (TRPC) channels have been implicated in mediating neuronal excitation induced by stimulating metabotropic receptors, including group 1 metabotropic glutamate receptors (mGluRs). Lateral septal (LS) neurons express high levels of TRPC4 and group I mGluRs. However, to what extent native TRPC4-containing channels (TRPC4-cc) are activated as well as the impact of different levels of TRPC4-cc activation on neuronal excitability remain elusive. Here, we report that stimulating LS neurons with group I mGluR agonist, (S)-3,5-DHPG, causes either an immediate increase in firing rate or an initial burst followed by a pause of firing, which can be correlated with below-threshold-depolarization (BTD) or above-threshold-plateau-depolarization (ATPD), respectively, in whole-cell recordings. The early phase of BTD and the entire ATPD are completely absent in neurons from TRPC4^?/? mice. Moreover, in the same LS neurons, BTD can be converted to ATPD at more depolarized potentials or with a brief current injection, suggesting that BTD and ATPD may represent partial and full activations of TRPC4-cc, respectively. We show that coincident mGluR stimulation and depolarization is required to evoke strong TRPC4-cc current, and Na⁺ and Ca²⁺ influx, together with dynamic changes of intracellular Ca²⁺, are essential for ATPD induction. Our results suggest that TRPC4-cc integrates metabotropic receptor stimulation with intracellular Ca²⁺ signals to generate two interconvertible depolarization responses to affect excitability of LS neurons in distinct fashions.     

A theory for amalgam forming electrode reactions

A theory for amalgam forming electrode reactions is formulated, based on a recently suggested extension of the Anderson model that allows a unified treatment of electron and ion transfer reactions. The predictions and classifications suggested by the model for both one- and two-electron transfer reactions are compared with earlier phenomenological theories and with experimental data.     

Comparison of the predictive performance of the BIG,TRISS, and PS09 score in an adult trauma population derived from multiple international trauma registries

Background

The BIG score (Admission base deficit (B), International normalized ratio (I), and Glasgow Coma Scale (G)) has been shown to predict mortality on admission in pediatric trauma patients. The objective of this study was to assess its performance in predicting mortality in an adult trauma population, and to compare it with the existing Trauma and Injury Severity Score (TRISS) and probability of survival (PS09) score.

Materials and methods

A retrospective analysis using data collected between 2005 and 2010 from seven trauma centers and registries in Europe and the United States of America was performed. We compared the BIG score with TRISS and PS09 scores in a population of blunt and penetrating trauma patients. We then assessed the discrimination ability of all scores via receiver operating characteristic (ROC) curves and compared the expected mortality rate (precision) of all scores with the observed mortality rate.

Results

In total, 12,206 datasets were retrieved to validate the BIG score. The mean ISS was 15 ± 11, and the mean 30-day mortality rate was 4.8%. With an AUROC of 0.892 (95% confidence interval (CI): 0.879 to 0.906), the BIG score performed well in an adult population. TRISS had an area under ROC (AUROC) of 0.922 (0.913 to 0.932) and the PS09 score of 0.825 (0.915 to 0.934). On a penetrating-trauma population, the BIG score had an AUROC result of 0.920 (0.898 to 0.942) compared with the PS09 score (AUROC of 0.921; 0.902 to 0.939) and TRISS (0.929; 0.912 to 0.947).

Conclusions

The BIG score is a good predictor of mortality in the adult trauma population. It performed well compared with TRISS and the PS09 score, although it has significantly less discriminative ability. In a penetrating-trauma population, the BIG score performed better than in a population with blunt trauma. The BIG score has the advantage of being available shortly after admission and may be used to predict clinical prognosis or as a research tool to risk stratify trauma patients into clinical trials.     

Basal asynchrony and resynchronization with biventricular pacing predict long-term improvement of LV function in heart failure patients

Biventricular pacing (BiV) is emerging for patients with dilated cardiomyopathy (DCM) and asynchrony. We measured basal asynchrony and early resynchronization by radionuclide angioscintigraphy (RNA) in order to predict long-term evolution of ventricular function after BiV. Thirty-four patients (NYHA Class III-IV,65.4 +/- 11 years) with large QRS(179 +/- 18 ms)were implanted with BiV and studied by RNA before (D0), at day 8 (D8), and during follow-up(20 +/- 7 months). We calculated left and right ejection fractions, the interventricular dyssynchrony (TRVLV), and the apicobasal dyssynchrony (Tab). LVEF improved from 20.2 +/- 8.1%(D0) to27.1%+/- 12.6%(follow-up,P < 0.003 vs D0) and RVEF from 28.6%+/- 13%(D0) to 34.3 +/- 11.5%(follow-up,P < 0.03 vs D0). Inter- (DeltaTRVLV) and intraventricular resynchronization was immediate and remained stable: TRVLV decreased from 68.3 +/- 38 ms(D0) to 13.4 +/- 48.5 ms(D8) and1.8 +/- 39.2 ms(follow-up,P < 0.0001 vs D0); and Tab from 45.8 +/- 64.1 msto-18 +/- 68(D8) and-28.3 +/- 53.6 ms(follow-up,P < 0.0001 vs D0). Early inter- and intraventricular resynchronization (DeltaTab) at D8 were related to late LVEF and RVEF improvement. Together, an LVEF > 15% and a significant interventricular dyssynchrony (TRVLV > 60 ms) at D0 have a sensitivity of 79% and a positive predictive value of 83% to predict an improvement of LVEF superior to 5% at follow-up. In DCM patients, BiV resynchronizes ventricles early and in the long-term, while RVEF and LVEF improve progressively. Patients with large electromechanical dyssynchrony benefit most from BiV.     

User and Healthcare Professional Perspectives on Do-It-Yourself Artificial Pancreas Systems: A Need for Guidelines

A growing number of individuals with type 1 diabetes are choosing to use “do-it-yourself” artificial pancreas systems (DIY APS) to support their diabetes self-management. Observational and self-report data of glycemic benefits of DIY APS are promising; however, without rigorous clinical trials or regulation from governing bodies, liability and user safety continue to be central concerns for stakeholders. Despite DIY APS having been used for several years now, there are no guidelines to assist users and healthcare professionals in addressing DIY APS use in routine clinical care. This commentary reports key stakeholders’ perspectives presented at the annual Advanced Technologies and Treatments in Diabetes conference in February 2020. Important considerations to inform the development of clinical care guidelines are also presented to generate further debate.     

Corrosion and Microstructural Investigation on Additively Manufactured 316L Stainless Steel: Experimental and Statistical Approach

The use of metal additive manufacturing (AM) has strongly increased in the industry during the last years. More specifically, selective laser melting (SLM) is one of the most used techniques due to its numerous advantages compared to conventional processing methods. The purpose of this study is to investigate the effects of process parameters on the microstructural and corrosion properties of the additively manufactured AISI 316L stainless steel. Porosity, surface roughness, hardness, and grain size were studied for specimens produced with energy densities ranging from 51.17 to 173.91 J/mm³ that resulted from different combinations of processing parameters. Using experimental results and applying the Taguchi model, 99.38 J/mm³ was determined as the optimal energy density needed to produce samples with almost no porosity. The following analysis of variance ANOVA confirmed the scanning speed as the most influential factor in reducing the porosity percentage, which had a 74.9% contribution, followed by the position along the building direction with 22.8%, and finally, the laser energy with 2.3%. The influence on corrosion resistance was obtained by performing cyclic potentiodynamic polarization tests (CPP) in a 3.5 wt % NaCl solution at room temperature for different energy densities and positions (Z axis). The corrosion properties of the AM samples were studied and compared to those obtained from the traditionally manufactured samples. The corrosion resistance of the samples worsened with the increase in the percentage of porosity. The process parameters have consequently been optimized and the database has been extended to improve the quality of the AM-produced parts in which microstructural heterogeneities were observed along the building direction.     

Burnout and professional quality of life among Israeli dentists: the role of sensory processing sensitivity

Aim: Dentistry is a stressful and exhausting profession with high levels of burnout. Sensory processing sensitivity (SPS) is a basic personality trait characterised by a gradient of sensitivity to both internal and external stimuli, including social and emotional cues. In this study, the influence of SPS on burnout and professional quality of life among Israeli dentists was analysed. Methods: Two-hundred and forty-three Israeli dentists responded to questionnaires that collected information on their SPS and professional quality of life (burnout, satisfaction at work and level of secondary traumatic stress), as well demographic variables, professional specialisation and workload. Results: Linear regression analyses showed that burnout can be predicted by the three aspects of SPS (ease of excitation, low sensory threshold and aesthetic sensitivity; 32% of the variance). Additionally, the same three aspects of SPS also predicted dentists’ satisfaction at work (24% of the variance). Ease of excitation and low sensory threshold, but not aesthetic sensitivity, predicted dentists’ reaction to their patients’ stress and trauma (23% of the variance). Conclusions: Sensory processing sensitivity can serve as a tool to identify dentists who are prone to develop burnout and whose professional quality of life can be adversely affected by their profession.Key words: Dentistry, sensory processing sensitivity, burnout, secondary traumatic stress, professional quality of life, compassion satisfaction