Clues of HLAs, metabolic SNPs, and epigenetic factors in T cell-mediated drug hypersensitivity reactions.

Drug hypersensitivities are common reactions due to immunologic responses. They are of utmost importance because they may generate severe and fatal outcomes. Some drugs may cause Adverse Drug Reactions (ADRs), such as drug hypersensitivity reactions (DHRs), which can occur due to the interaction of intact drugs or their metabolites with Human Leukocyte Antigens (HLAs) and T cell receptors (TCRs). This type develops over a period of 24-72 h after exposure and is classified as type IV of DHRs. Acute generalized exanthematic pustulosis (AGEP), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are types of Severe Cutaneous Adverse Reactions (SCARs). In this review, we aim to discuss the types of ADRs, the mechanisms involved in their development, and the role of immunogenetic factors, such as HLAs in type IV DHRs, single-nucleotide polymorphisms (SNPs), and some epigenetic modifications, e.g., DNA/histone methylation in a variety of genes and their promoters which may predispose subjects to DHRs. In conclusion, development of promising novel in vitro or in vivo diagnostic and prognostic markers is essential for identifying susceptible subjects or providing treatment protocols to work up patients with drug allergies as personalized medicine.

Ultra-high-granularity detector simulation with intra-event aware generative adversarial network and self-supervised relational reasoning.

Simulating high-resolution detector responses is a computationally intensive process that has long been challenging in Particle Physics. Despite the ability of generative models to streamline it, full ultra-high-granularity detector simulation still proves to be difficult as it contains correlated and fine-grained information. To overcome these limitations, we propose Intra-Event Aware Generative Adversarial Network (IEA-GAN). IEA-GAN presents a Transformer-based Relational Reasoning Module that approximates an event in detector simulation, generating contextualized high-resolution full detector responses with a proper relational inductive bias. IEA-GAN also introduces a Self-Supervised intra-event aware loss and Uniformity loss, significantly enhancing sample fidelity and diversity. We demonstrate IEA-GAN's application in generating sensor-dependent images for the ultra-high-granularity Pixel Vertex Detector (PXD), with more than 7.5 M information channels at the Belle II Experiment. Applications of this work span from Foundation Models for high-granularity detector simulation, such as at the HL-LHC (High Luminosity LHC), to simulation-based inference and fine-grained density estimation.

Evaluation of the prevalence of cardiometabolic disorders (diabetes, hypertension, and hyperlipidemia) diagnosed, undiagnosed, treated, and treatment goal in the elderly: Bushehr Elderly Health Program (BEH).

As the population ages, the global burden of cardiometabolic disorders will increase. This study aimed to investigate the prevalence of cardiometabolic disorders (diabetes, hypertension, and hyperlipidemia) in elderly and to evaluate the effects of various variables including age, sex, education, marital status, smoking, income, physical activity, dementia and depressed mood on untreated cardiometabolic disorders. This was a cross sectional study conducted in Bushehr Elderly Health Program. A total 2381 participants were included. Medical data were collected by trained interviewers. The mean age of the study participants was 69.34 years. Proportions of diabetes, hypertension, hyperlipidemia and hypercholesterolemia were 43.25%, 75.71%, 64.74% and 35.31% respectively. Untreated diabetes prevalence was higher for males (OR = 1.60, 95%CI = 1.20-2.15), older adults (OR = 1.02, 95%CI = 1.00-1.05), and pre-frail status (OR = 0.69, 95%CI = 0.52-0.92). Males (OR = 2.16, 95%CI = 1.64-2.84) and current smokers (OR = 1.42, 95%CI = 1.05-1.93), in contrast to married participants (OR = 0.25, 95%CI = 0.08-0.78), people with higher education levels (OR = 0.51, 95%CI = 0.29-0.89) and dementia (OR = 0.78, 95%CI = 0.61-1.00) were more likely to have untreated HTN. Untreated dyslipidemia is more common in smokers (OR = 1.78, 95%CI = 1.19-2.66) and males (OR = 1.66, 95%CI = 1.21-2.27), while untreated hypercholesteremia is more common in males (OR = 3.20, 95%CI = 1.53-6.69) and is reported lower in people with dementia (OR = 0.53, 95%CI = 0.28-1.01).

Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis.

OBJECTIVE: We aimed to conduct a systematic review and meta-analysis of clinical trials that examined the effects of L-citrulline supplementation on blood pressure (BP). MATERIALS AND METHODS: We searched MEDLINE, SCOPUS, PUBMED and Google scholar databases from inception to November 16, 2017 and 811 papers were identified, of which 8 trials with 10 data sets met the inclusion criteria. Inclusion criteria were: (1) application of randomized clinical trial with either crossover or parallel designs; (2) studies conducted in adults (≥18 y); (3) oral supplementation with L-citrulline compared to control group; (4) expression of sufficient data about systolic and diastolic BP at baseline and at the end of the study in each group. BP effects were pooled by random-effects models, with trials weighted by inverse variance. RESULTS: The included studies' sample size ranged between 12 and 34 subjects. The mean age of the participants in these trials ranged between 22 and 71 years. Dosage of L-citrulline supplementation varied from 3 to 9 g/day. Duration of the intervention ranged between 1 and 17 weeks. The pooled changes in systolic and diastolic BP were (MD, -4.10 mm Hg; 95% CI [-7.94, -0.26]; p=0.037) and (MD -2.08 mm Hg; 95% CI [-4.32, 0.16]; P=0.069), respectively. The subgroup analysis showed a significant diastolic BP reduction in studies that used doses of ≥6 g/day (MD -2.75 mm Hg; 95% CI [-5.37, -0.12]; p=0.04). CONCLUSION: Our results suggest that L-citrulline supplementation may reduce systolic BP. A significant reduction in diastolic BP was observed only in the studies that used doses ≥ 6 g/day.