Impact of chronic ethanol consumption and SARS-COV-2 on the liver and intestine: A pilot dose-response study in mice.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a marked increase in alcohol consumption. COVID-19 superimposed on underlying liver disease notably worsens the outcome of many forms of liver injury. The goal of a current pilot study was to test the dual exposure of alcohol and COVID-19 infection in an experimental animal model of alcohol-associated liver disease (ALD).

Harnessing global HLA data for enhanced patient matching in iPSC haplobanks.

Background: Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This 'haplobank' approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype.

Aims: A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank.

Bacterial and host fucosylation maintain IgA homeostasis to limit intestinal inflammation in mice.

Inflammatory bowel disease is associated with several genetic risk loci. Loss-of-function mutation in the α1,2-fucosyltransferase (fut2) gene, which alters fucosylation on the surface of intestinal epithelial cells, is one example. However, whether bacterial fucosylation can contribute to gut inflammation is unclear.

Visium spatial transcriptomics and proteomics identifies novel hepatic cell populations and transcriptomic signatures of alcohol-associated hepatitis.

Background: Alcohol-associated hepatitis (AH) is the clinical manifestation of alcohol-associated liver disease (ALD). AH is a complex disease encompassing the dysregulation of many cells and cell subpopulations. This study used a hepatic spatial transcriptomic and proteomic approach (10X Genomics Visium) to identify hepatic cell populations and their associated transcriptomic and proteomic alterations in human AH.

Intestine epithelial-specific hypoxia-inducible factor-1α overexpression ameliorates western diet-induced MASLD.

Background: Intestine epithelial hypoxia-inducible factor-1α (HIF-1α) plays a critical role in maintaining gut barrier function. The aim of this study was to determine whether pharmacological or genetic activation of intestinal HIF-1α ameliorates western diet-induced metabolic dysfunction-associated steatotic liver disease.

Methods: Metabolic effects of pharmacological activation of HIF-1α by dimethyloxalylglycine were evaluated in HIF-α luciferase reporter (ODD-luc) mice.

Condo or cuisine? The function of fine woody debris in driving decomposition, detritivores, and their predators.

Community structure and ecosystem function may be driven by the size or the energy within a given habitat, but these metrics (space and energy) are difficult to separate, especially in systems where the habitat itself is also food, such as detritus. Only a handful of studies have attempted to isolate potential mechanisms experimentally, which has left a notable knowledge gap in understanding the drivers of community structure and function. Here, we tested whether fine woody debris (FWD) affects leaf litter communities primarily as a source of space or energy.

Environmentally sustainable surgical systems.

Surgeons, anaesthetists, wider surgical teams and hospital managers are a large global group that has the capacity and power to play a leadership role to contribute to change. Hospitals are a good target for improvement since they are centres of communities, linking together surrounding healthcare facilities and influencing wider determinants of the environment. District and rural hospitals are good sites to start since they serve large populations, have the least sustained energy and clean water supplies and will benefit most from quality improvement.

T cell epitope mapping reveals immunodominance of evolutionarily conserved regions within SARS-CoV-2 proteome.

As SARS-CoV-2 variants continue to emerge capable of evading neutralizing antibodies, it has become increasingly important to fully understand the breadth and functional profile of T cell responses to determine their impact on the immune surveillance of variant strains. Here, sampling healthy individuals, we profiled the kinetics and polyfunctionality of T cell immunity elicited by mRNA vaccination. Modeling of anti-spike T cell responses against ancestral and variant strains of SARS-CoV-2 suggested that epitope immunodominance and cross-reactivity are major predictive determinants of T cell immunity.

Controls on regional sulphate distribution in shallow groundwater in the western Canadian Interior Plains.

Sulphate (SO), predominantly derived from sulphur (S)-bearing glacial sediments distributed widely across the Canadian Interior Plains, contributes to high groundwater salinity and can be detrimental to riparian and dry-land ecosystems, agricultural production, and water use. While previous researchers investigated SO distribution and dynamics in shallow groundwater at local scales (<1500 km), we examine SO occurrence in groundwater at larger scales, and to depths of ∼150 m, considering variations in geology, glacial history, climate, and geochemical and hydrogeological settings in the Canadian province of Alberta. Sulphate concentrations in groundwater vary considerably, with 15 % of 139,130 samples above the 500 mg/L Canadian drinking water aesthetic objective.

Multiomics Studies on Metabolism Changes in Alcohol-Associated Liver Disease.

Metabolic dysfunction in the liver represents a predominant feature in the early stages of alcohol-associated liver disease (ALD). However, the mechanisms underlying this are only partially understood. To investigate the metabolic characteristics of the liver in ALD, we did a relative quantification of polar metabolites and lipids in the liver of mice with experimental ALD using untargeted metabolomics and untargeted lipidomics.

Wipe Disinfection of Reusable Elastomeric Half-Mask Respirators for Health Care Use.

Background: During shortages, elastomeric half-mask respirators (EHMRs) are an alternative to reusing N95 filtering facepiece respirators but require between-use disinfection. The objectives of this study were to (a) measure microbial reductions on EHMR surfaces under laboratory conditions by a standardized procedure using wipes impregnated with health care disinfectants and to (b) measure microbial reductions on EHMRs disinfected by volunteer health care providers.

Method: We inoculated EHMR (Honeywell model RU8500) surfaces with spores, and bacteriophages MS2 and Φ6, and disinfected them using two wipes with hydrogen peroxide (HP), alcohols, and quaternary ammonium compounds (QACs).

Hepatic Proteomic Changes Associated with Liver Injury Caused by Alcohol Consumption in Mice.

Alcohol-associated liver disease (ALD) is a prevalent medical problem with limited effective treatment strategies. Although many biological processes contributing to ALD have been elucidated, a complete understanding of the underlying mechanisms is still lacking. The current study employed a proteomic approach to identify hepatic changes resulting from ethanol (EtOH) consumption and the genetic ablation of the formyl peptide receptor 2 (FPR2), a G-protein coupled receptor known to regulate multiple signaling pathways and biological processes, in a mouse model of ALD.

Experiences when using different EHMR models: Implications for different designs and meeting user expectations.

Background: New elastomeric half-mask respirator (EHMR) models without exhalation valves (EVs) or with exhalation valve filters (EVFs) are facilitating expanded use in health settings to reduce workers' exposure to airborne hazards while acting as source control to prevent pathogen spread. The physical comfort of new models has not been assessed in comparison to previously used EHMRs with EVs.

Methods: Researchers assessed 1,962 health care and emergency medical service personnels' self-reported adverse experiences from 2 cohorts while wearing EHMR models with EVs (cohort 1, n = 1,080) and without EVs or with EVFs (cohort 2, n = 882).

Age-associated temporal decline in butyrate-producing bacteria plays a key pathogenic role in the onset and progression of neuropathology and memory deficits in 3×Tg-AD mice.

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD.

Evaluation of Apixaban Use in Patients With Advanced Kidney Disease.

Current guidelines and literature suggest apixaban may be used in patients with severe kidney disease and atrial fibrillation (AF) for stroke and systemic embolism risk reduction (SSE) or patients with acute venous thromboembolism (VTE). Limited data is available for long-term safety and efficacy outcomes in this patient population. Evaluate the use of apixaban for AF or VTE in patients with advanced kidney disease.

Task-sharing spinal anaesthesia care in three rural Indian hospitals: a non-inferiority randomised controlled clinical trial.

Background: Task-sharing of spinal anaesthesia care by non-specialist graduate physicians, termed medical officers (MOs), is commonly practised in rural Indian healthcare facilities to mitigate workforce constraints. We sought to assess whether spinal anaesthesia failure rates of MOs were non-inferior to those of consultant anaesthesiologists (CA) following a standardised educational curriculum.

Methods: We performed a randomised, non-inferiority trial in three rural hospitals in Tamil Nadu and Chhattisgarh, India.

Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone.

Background And Aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach And Results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed.

Peripherally Restricted CB1 Receptor Inverse Agonist JD5037 Treatment Exacerbates Liver Injury in MDR2-Deficient Mice.

Previous research highlighted the involvement of the cannabinoid CB1 receptor in regulating the physiology of hepatocytes and hepatic stellate cells. The inhibition of the CB1 receptor via peripherally restricted CB1 receptor inverse agonist JD5037 has shown promise in inhibiting liver fibrosis in mice treated with CCl4. However, its efficacy in phospholipid transporter-deficiency-induced liver fibrosis remains uncertain.

Association of Circulating Markers of Microbial Translocation and Hepatic Inflammation with Liver Injury in Patients with Type 2 Diabetes.

Background: Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased microbial translocation and systemic inflammation in the development of liver injury in patients with T2DM.