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Abstract Objective Improving care transitions for older adults can reduce emergency department (ED) visits, adverse events, and empower community autonomy. We conducted an inductive qualitative content analysis to identify themes emerging from comments to better understand ED care transitions. Methods The LEARNING WISDOM prospective longitudinal observational cohort includes older adults (≥ 65 years) who experienced a care transition after an ED visit from both before and during COVID-19. Their comments on this transition were collected via phone interview and transcribed. We conducted an inductive qualitative content analysis with randomly selected comments until saturation. Themes that arose from comments were coded and organized into frequencies and proportions. We followed the Standards for Reporting Qualitative Research (SRQR). Results Comments from 690 patients (339 pre-COVID, 351 during COVID) composed of 351 women (50.9%) and 339 men (49.1%) were analyzed. Patients were satisfied with acute emergency care, and the proportion of patients with positive acute care experiences increased with the COVID-19 pandemic. Negative patient comments were most often related to communication between health providers across the care continuum and the professionalism of personnel in the ED. Comments concerning home care became more neutral with the COVID-19 pandemic. Conclusion Patients were satisfied overall with acute care but reported gaps in professionalism and follow-up communication between providers. Comments may have changed in tone from positive to neutral regarding home care over the COVID-19 pandemic due to service slowdowns. Addressing these concerns may improve the quality of care transitions and provide future pandemic mitigation strategies.

BackgroundClinical decision support systems are information technologies that assist clinicians in making better decisions. Their adoption has been limited because their content is difficult to adapt to local contexts and slow to adapt to emerging evidence. Collaborative writing applications such as wikis have the potential to increase access to existing and emerging evidence-based knowledge at the point of care, standardize emergency clinical decision making, and quickly adapt this knowledge to local contexts. However, little is known about the factors influencing health professionals’ use of wiki-based knowledge tools. ObjectiveThis study aims to measure emergency physicians’ (EPs) and other acute care health professionals’ (ACHPs) intentions to use wiki-based knowledge tools in trauma care and identify determinants of this intention that can be used in future theory-based interventions for promoting the use of wiki-based knowledge tools in trauma care. MethodsIn total, 266 EPs and 907 ACHPs (nurses, respiratory therapists, and pharmacists) from 12 Quebec trauma centers were asked to answer a survey based on the theory of planned behavior (TPB). The TPB constructs were measured using a 7-point Likert scale. Descriptive statistics and Pearson correlations between the TPB constructs and intention were calculated. Multiple linear regression analysis was conducted to identify the salient beliefs. ResultsAmong the eligible participants, 57.1% (152/266) of EPs and 31.9% (290/907) of ACHPs completed the questionnaire. For EPs, we found that attitude, perceived behavioral control (PBC), and subjective norm (SN) were significant determinants of the intention to use wiki-based knowledge tools and explained 62% of its variance. None of the sociodemographic variables were related to EPs’ intentions to use wiki-based knowledge tools. The regression model identified two normative beliefs ("approval by physicians" and "approval by patients") and two behavioral beliefs ("refreshes my memory" and "reduces errors"). For ACHPs, attitude, PBC, SN, and two sociodemographic variables (profession and the previous personal use of a wiki) were significantly related to the intention to use wiki-based knowledge tools and explained 60% of the variance in behavioral intention. The final regression model for ACHPs included two normative beliefs ("approval by the hospital trauma team" and "people less comfortable with information technology"), one control belief ("time constraints"), and one behavioral belief ("access to evidence"). ConclusionsThe intentions of EPs and ACHPs to use wiki-based knowledge tools to promote best practices in trauma care can be predicted in part by attitude, SN, and PBC. We also identified salient beliefs that future theory-based interventions should promote for the use of wiki-based knowledge tools in trauma care. These interventions will address the barriers to using wiki-based knowledge tools, find ways to ensure the quality of their content, foster contributions, and support the exploration of wiki-based knowledge tools as potential effective knowledge translation tools in trauma care.

Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made toward the development of miRNA-based therapeutics for human disorders. This study was designed to evaluate the efficiency and potential safety of miRNA replacement therapy in AD, using miR-15/107 paralogues as candidate drug targets. We identified miR-16 as a potent inhibitor of amyloid precursor protein (APP) and BACE1 expression, Aβ peptide production, and Tau phosphorylation in cells. Brain delivery of miR-16 mimics in mice resulted in a reduction of AD-related genes APP, BACE1, and Tau in a region-dependent manner. We further identified Nicastrin, a γ-secretase component involved in Aβ generation, as a target of miR-16. Proteomics analysis identified a number of additional putative miR-16 targets in vivo, including α-Synuclein and Transferrin receptor 1. Top-ranking biological networks associated with miR-16 delivery included AD and oxidative stress. Collectively, our data suggest that miR-16 is a good candidate for future drug development by targeting simultaneously endogenous regulators of AD biomarkers (i.e., Aβ and Tau), inflammation, and oxidative stress.

MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as sensors of extracellular sodium concentration ([Na+]out). The mechanism underlying Na+-sensing involves Na+-flow through the NaX channel, directly regulated by the Na+/K+-ATPase α1-isoform which controls Na+-influx by modulating channel permeability. Together, these two partners form a complex involved in the regulation of intracellular sodium ([Na+]in). Here we aim to determine whether environmental changes in Na+ could actively modulate the NaX/Na+/K+-ATPase complex activity.We investigated the complex activity using patch-clamp recordings from rat MnPO neurons and Neuro2a cells. When the rats were fed with a high-salt-diet, or the [Na+] in the culture medium was increased, the activity of the complex was up-regulated. In contrast, drop in environmental [Na+] decreased the activity of the complex. Interestingly under hypernatremic condition, the colocalization rate and protein level of both partners were up-regulated. Under hyponatremic condition, only NaX protein expression was increased and the level of NaX/Na+/K+-ATPase remained unaltered. This unbalance between NaX and Na+/K+-ATPase pump proportion would induce a bigger portion of Na+/K+-ATPase-control-free NaX channel. Thus we suggest that hypernatremic environment increases NaX/Na+/K+-ATPase α1-isoform activity by increasing the number of both partners and their colocalization rate, whereas hyponatremic environment down-regulates complex activity via a decrease in the relative number of NaX channels controlled by the pump.

Reaching a surface temperature of 50 °C in a heavily populated region, like Paris, would have devastating effects. Although such a high value seems far from the present-day record of 42.6 °C, its occurrence cannot be dismissed by the end of the 21st century, due to the continuous increase of global mean temperature. In this paper, we address two questions that were asked by the City of Paris to a group of scientists: When does this event start to be likely? What are the prevailing meteorological conditions? We base our study on the CMIP6 simulation ensemble. Many of the CMIP6 yield biases in temperature. Rather than using methods of bias correction, which are not necessarily adapted to high extremes, we propose a pragmatic approach of model selection in order to seek such high temperature events that are deemed realistic. We analyze the meteorological conditions leading to first occurrences of such hot events and their common atmospheric patterns. This paper describes a simple data mining approach (on a large ensemble of climate model simulations) which could be adapted to other regions of the world, in order to help decision makers anticipating and adapting to such devastating meteorological events.

Summary: The mechanical environment generated through the adhesive interaction of endothelial cells (ECs) with the matrix controls nuclear tension, preventing aberrant gene synthesis and the transition from restrictive to leaky endothelium, a hallmark of acute lung injury (ALI). However, the mechanisms controlling tension transmission to the nucleus and EC-restrictive fate remain elusive. Here, we demonstrate that, in a kinase-independent manner, focal adhesion kinase (FAK) safeguards tension transmission to the nucleus to maintain EC-restrictive fate. In FAK-depleted ECs, robust activation of the RhoA-Rho-kinase pathway increased EC tension and phosphorylation of the nuclear envelope protein, emerin, activating DNMT3a. Activated DNMT3a methylates the KLF2 promoter, impairing the synthesis of KLF2 and its target S1PR1 to induce the leaky EC transcriptome. Repleting FAK (wild type or kinase dead) or inhibiting RhoA-emerin-DNMT3a activities in damaged lung ECs restored KLF2 transcription of the restrictive EC transcriptome. Thus, FAK sensing and control of tension transmission to the nucleus govern restrictive endothelium to maintain lung homeostasis.