GABA-mediated inhibition of human CD4 T cell functions is enhanced by insulin but impaired by high glucose levels.

Background: γ-aminobutyric acid (GABA), known as the main inhibitory neurotransmitter in the brain, exerts immunomodulatory functions by interaction with immune cells, including T cells. Metabolic programs of T cells are closely linked to their effector functions including proliferation, differentiation, and cytokine production. The physiological molecules glucose and insulin may provide environmental cues and guidance, but whether they coordinate to regulate GABA-mediated T cell immunomodulation is still being examined.

Microbiological hazard identification in river waters used for recreational activities.

Pathogenic bacteria, viruses, and parasites can cause waterborne disease outbreaks. The study of coastal water quality contributes to identifying potential risks to human health and to improving water management practices. The Río de la Plata River, a wide estuary in South America, is used for recreational activities, as a water source for consumption and as a site for sewage discharges.

GABA signalling in human pancreatic islets.

The pancreatic islets are essential microorgans controlling the glucose level in the blood. The islets consist of different cell types which communicate with each other by means of auto- and paracrine interactions. One of the communication molecules produced by and released within the islets is γ-aminobutyric acid (GABA), a well-known inhibitor of neuronal excitability in the mammalian nervous system.

Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against and .

We have developed compounds with a promising activity against and , which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor , we identified compound , featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from and , a 10-fold decreased inhibition of human topoisomerase IIα, and no cross-resistance to novobiocin. Cocrystal structures of in complex with GyrB24 and ()- in complex with GyrB23 and GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit.

ZEB2 haploinsufficient Mowat-Wilson syndrome induced pluripotent stem cells show disrupted GABAergic transcriptional regulation and function.

Mowat-Wilson syndrome (MWS) is a severe neurodevelopmental disorder caused by heterozygous variants in the gene encoding transcription factor . Affected individuals present with structural brain abnormalities, speech delay and epilepsy. In mice, conditional loss of Zeb2 causes hippocampal degeneration, altered migration and differentiation of GABAergic interneurons, a heterogeneous population of mainly inhibitory neurons of importance for maintaining normal excitability.

MEDICATION ADHERENCE AND ITS IMPACT ON THE AVERAGE LIFE EXPECTANCY AFTER ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: THE RESULTS OF THE UKRAINIAN STIMUL REGISTRY.

Objective: The aim: The present study aimed to evaluate the adherence to medications prior and within a two-year period after ST-segment elevation myocardial infarction (STEMI) and to estimate its impact on the average lifespan of patients after STEMI.

Patients And Methods: Materials and methods: 1,103 patients with STEMI were enrolled in the prospective Ukrainian STIMUL registry with 24-month follow-up. The relationship between adherence to medical treatment and average lifespan was evaluated.

Evaluation and Comparison of the STIMUL Extended and Simplified Risk Scores for Predicting Two-Year Death in Patients Following ST-Segment Elevation Myocardial Infarction.

The management of ST-segment elevation myocardial infarction (STEMI) requires a patient's long-term risk to be estimated. The objective of this study was to develop extended and simplified models of two-year death risk estimation following STEMI that include and exclude cardiac troponins as prognostic factors and to compare their performance with each other. : Extended and simplified multivariable logistic regression models were elaborated using 1103 patients with STEMI enrolled and followed up in the STIMUL (ST-segment elevation Myocardial Infarctions in Ukraine and their Lethality) registry.

STRENGTHENING STUDENTS' HEALTH IN THE PROCESS OF SPORTS AND HEALTH TOURISM ENGAGEMENT.

Objective: The aim: Is to investigate the level and dynamics of students' physical health in the process of sports and health tourism engagement.

Patients And Methods: Materials and methods: The research involved the students (men) of Sumy State University (n = 60). The research was conducted in 2018-2020.

Brief Mental Health Disorder Screening Questionnaires and Use with Public Safety Personnel: A Review.

Brief mental health disorder screening questionnaires (SQs) are used by psychiatrists, physicians, researchers, psychologists, and other mental health professionals and may provide an efficient method to guide clinicians to query symptom areas requiring further assessment. For example, annual screening has been used to help identify military personnel who may need help. Nearly half (44.

ANALYSIS OF STUDENTS' SOMATIC HEALTH AND EMOTIONAL STATE DURING SPORTS GAMES CLASSES.

Objective: The aim: Is to investigate the impact of sports games (football) on the level of somatic health and emotional state of students in the process of studying.

Patients And Methods: Materials and methods: The study was conducted at Kharkiv State Academy of Physical Culture and Sumy State University (Ukraine) in 2018-2019. The study involved 87 male students of the main department.

Demographic and cognitive risk factors for police mental disorder symptoms.

The current study was designed to assess whether cognitive risk factors (i.e. anxiety sensitivity (AS), intolerance of uncertainty (IU)) explained variance in mental disorder symptoms in Canadian police officers beyond variance explained by demographic variables (i.

Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age-dependent manner, normalizes GABA-activated currents in the tg-APPSwe mouse model of Alzheimer's disease.

Aim: We examined if tonic γ-aminobutyric acid (GABA)-activated currents in primary hippocampal neurons were modulated by insulin in wild-type and tg-APPSwe mice, an Alzheimer's disease (AD) model.

Methods: GABA-activated currents were recorded in dentate gyrus (DG) granule cells and CA3 pyramidal neurons in hippocampal brain slices, from 8 to 10 weeks old (young) wild-type mice and in dorsal DG granule cells in adult, 5-6 and 10-12 (aged) months old wild-type and tg-APPSwe mice, in the absence or presence of insulin, by whole-cell patch-clamp electrophysiology.

Results: In young mice, insulin (1 nmol/L) enhanced the total spontaneous inhibitory postsynaptic current (sIPSC ) density in both dorsal and ventral DG granule cells.

Evaluation of bottled water quality by determining nitrate concentration.

The presence of nitrate in sources of drinking water is a matter of concern because of its potential risk for human health. In many countries like Argentina, an increasing proportion of the population chooses to consume bottled water, among other reasons, for lack of water access. The present study was conducted (a) to evaluate the quality of bottled waters by determining nitrate concentration, (b) to relate bottled water quality with water access, (c) to analyze public awareness about bottled water quality and consumption habits of the population in the urban area of Buenos Aires.

A genetic association study of heart failure: more evidence for the role of BAG3 in idiopathic dilated cardiomyopathy.

Aims: Few investigations have been conducted to identify genetic determinants of common, polygenetic forms of heart failure (HF), and only a limited number of these genetic associations have been validated by multiple groups.

Methods And Results: We performed a case-control study to further investigate the potential impact of 14 previously reported candidate genes on the risk of HF and specific HF sub-types. We also performed an exploratory genome-wide study.

Tonic GABA-activated synaptic and extrasynaptic currents in dentate gyrus granule cells and CA3 pyramidal neurons along the mouse hippocampal dorsoventral axis.

The hippocampus is a medial temporal lobe structure in the brain and is widely studied for its role in memory and learning, in particular, spacial memory and emotional responses. It was thought to be a homogenous structure but emerging evidence shows differentiation along the dorsoventral axis and even microdomains for functional and cellular markers. We have examined in two cell-types of the hippocampal projection neurons, the dentate gyrus (DG) granule cells and CA3 pyramidal neurons, if the GABA-activated tonic current density varied between the dorsal (septal) and the ventral (temporal) poles of the male mouse hippocampus.

GABA Receptor-Mediated Currents and Hormone mRNAs in Cells Expressing More Than One Hormone Transcript in Intact Human Pancreatic Islets.

In pancreatic islets, the major cell-types are α, β and δ cells. The γ-aminobutyric acid (GABA) signalling system is expressed in human pancreatic islets. In single hormone transcript-expressing cells, we have previously characterized the functional properties of islet GABA receptors (iGABARs).

Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers.

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers.

Evaluating the efficacy of an attention modification program for patients with fibromyalgia: a randomized controlled trial.

Persons with chronic musculoskeletal pain may be hypervigilant for pain-related cues which, paradoxically, may be maintaining their pain. Several randomized controlled trials have assessed whether a modified dot-probe protocol (ie, attention bias modification [ABM]) reduces chronic pain- and pain-related symptoms in persons with several diagnoses, including fibromyalgia. Scalability and economic efficiency potentiates the appeal of ABM protocols; however, research results have been mixed, with only some studies evidencing significant symptom gains from ABM and some evidencing gains for the control group.

Interferon-γ potentiates GABA receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons.

The neural transmission and plasticity can be differentially modulated by various elements of the immune system. Interferon-γ (IFN-γ) is a "pro-inflammatory" cytokine mainly produced by T lymphocytes, activates its corresponding receptor and plays important roles under both homeostatic and inflammatory conditions. However, the impact of IFN-γ on the γ-aminobutyric acid (GABA)-mediated currents in the hippocampus, a major brain region involved in the cognitive function, has not been investigated.

Transcriptomes of Dravet syndrome iPSC derived GABAergic cells reveal dysregulated pathways for chromatin remodeling and neurodevelopment.

Dravet syndrome (DS) is an early onset refractory epilepsy typically caused by de novo heterozygous variants in SCN1A encoding the α-subunit of the neuronal sodium channel Na1.1. The syndrome is characterized by age-related progression of seizures, cognitive decline and movement disorders.

Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality.

We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia.

Is there a potential association between spironolactone and the risk of new-onset diabetes in a cohort of older patients with heart failure?

Purpose: Some evidence suggests that spironolactone may have a deleterious effect on glucose homeostasis. The objective of this study was to assess whether spironolactone use is associated with a higher risk of developing diabetes in a large cohort of patients with heart failure (HF).

Methods: Two Quebec government administrative databases were used to identify a cohort of hospitalized patients discharged between January 1995 and December 2009 with a primary discharge diagnosis of HF and without secondary discharge diagnosis of diabetes.

Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes.

Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.