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Drug-induced liver injury (DILI) is a serious complication of many drugs, including carbamazepine; this study investigates the protective effect of pentoxifylline (PTX) against DILI induced by carbamazepine in rat models by attenuating CYP3A4 and NF-κB gene expression. Forty rats were divided into five groups: the control group received no treatment, the induction group received 50 mg/kg carbamazepine orally for 28 days, and three groups received PTX (100, 200, and 300 mg/kg) once daily for one hour before carbamazepine induction for 28 days. Then, the rats were euthanized, and blood and liver tissue were collected for biochemical, gene expression, and histopathology. PTX attenuates the carbamazepine-induced increased CYP3A4 and NF-κB gene expression, with the highest dose showing the best result. PTX also reduced aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, while glutathione levels increased. In conclusion, PTX is highly efficacious in preventing and restoring the liver cells’ normal morphology and cellular function caused by carbamazepine hepatotoxicity. A possible mechanism of the PTC effect is hindering oxidative stress by scavenging free radicals and enhancing the body’s natural defense antioxidant system. Additionally, it exerts an anti-inflammatory impact by modulating NF-κB gene expression.

Early nutritional management approach greatly impacts broilers’ performance and resistance against coccidiosis. The current study explored the impact of post-hatch feeding with a combination of glutamine (Glut) and different levels of omega-3 on broiler chickens’ growth performance, muscle building, intestinal barrier, antioxidant ability and protection against avian coccidiosis. A total of six hundred Cobb 500 was divided into six groups: first group (fed basal diet and unchallenged (control) and challenged (negative control, NC) groups were fed a basal diet without additives, and the other groups were infected with Eimeria spp and supplemented with 1.5% Glut alone or with three different levels of omega-3 (0.25, 0.5 and 1%) during the starter period. Notable improvement in body weight gain was observed in the group which fed basal diet supplemented with glut and 1% omega 3 even after coccidia infection (increased by 25% compared challenged group) while feed conversion ratio was restored to control. Myogeneis was enhanced in the group supplemented with Glut and omega-3 (upregulation of myogenin, MyoD, mechanistic target of rapamycin kinase and insulin like growth factor-1 and downregulating of myostatin genes). Groups supplemented with Glut and higher levels of omega-3 highly expressed occluding, mucin-2, junctional Adhesion Molecule 2, b-defensin-1 and cathelicidins-2 genes. Group fed 1% Glut + omega-3 showed an increased total antioxidant capacity and glutathione peroxidase and super oxide dismutase enzymes activities with reduced levels of malondialdehyde, reactive oxygen species and H2O2. Post-infection, dietary Glut and 1% omega-3 increased intestinal interleukin-10 (IL) and secretory immunoglobulin-A and serum lysozyme, while decreased the elevated inflammatory mediators comprising interleukin IL-6, tumor necrosis factor-alpha, nitric oxide (NO) and inducible NO synthase. Fecal oocyst excretion and lesions score severity were lowered in the group fed 1% Glut and omega 3. Based on these findings, dietary Glut and omega-3 supplementation augmented restored overall broilers’ performance after coccidial challenge.

Cannabidiol (CBD) found in Cannabis sativa is a non-psychoactive compound which is capable of binding to CB1 and CB2 receptors. CBD has recently gained interest in dentistry although it has not been explored sufficiently yet. The therapeutic effects of CBD include anti-inflammatory, analgesic, antioxidant, biological and osteoinductive properties. The aim of this review is to highlight these effects with respect to various oral conditions and shed light on the current limitations and prospects for the use of CBD in maintaining oral health.

Background: The adulteration of milk is an important issue that needs to be addressed because of its deleterious effects on health. Detection of adulterants in milk can be done in laboratories or by purchasing adulteration detection kits. There are few home-based rapid tests to detect common milk adulterants, which are less known by our community. Objectives of this study were to estimate the proportion of milk adulteration and to identify common adulterants, to determine the association of milk adulteration with gastrointestinal and renal diseases; and also to validate rapid home-based tests by comparing its result with standard milk adulteration detection kit. Materials and Methods: A community-based study was conducted on 330 medical and paramedical staff. Collected milk samples during family visits were tested by standard milk adulteration detection tests and rapid home-based tests. Results: Among 330 tested milk samples, 233 samples were adulterated with one or more than one adulterant. The most common adulteration observed was the addition of water to milk, followed by detergent, urea, and neutralizer. The specificity of the rapid tests was found to be almost 100% in the detection of water and detergent in milk and accuracy was above 80%; with “substantial agreement” (kappa = 0.7) between rapid tests and standard tests on kappa statistics. Conclusion: The present study has identified a large extent of milk adulteration and common adulterants, which may have harmful effects on health. The utility of home-based rapid tests is clearly proven to detect common adulterants.

Current research aims to assess the therapeutic impact of Mucuna pruriens seed extract on PROTAMIN (PRM) I and II gene expression and hormones in chlorpromazine-induced endocrine disruptions and reproductive toxicity in male rats. Thirty male Wistar rats were categorized into five groups: the negative control group, rats that received distilled water for 52 days; the induction group, rats that received (20 mg/kg) of chlorpromazine for 52 days; and three treatment groups that were pretreated with chlorpromazine (similar to the induction group) that received a low, medium, and high dose of Mucuna pruriens (500, 1000, and 2000 mg/kg, respectively). Serum samples were collected to measure testosterone, FSH (follicular stimulating hormone), LH (luteinizing hormone), and prolactin serum levels using the ELISA technique. Tissue samples were collected to measure PRM I and II gene expression and for histopathological study. The PRM I and II genes were significantly downregulated in the chlorpromazine-treated group. These genes were also significantly upregulated in Mucuna pruriens-treated groups. The Mucuna pruriens-treated groups revealed a significant rise in serum LH, testosterone, and FSH concentrations, decreased serum prolactin, and improved histology of testicular damage compared to the induction group. In conclusion, the endocrine disruption and hormonal changes induced by chlorpromazine improved when Mucuna pruriens was administered, improving the impairment in gene expression and hormones.

Abstract Background Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. Methods 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. Results Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p

Abstract Background Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. Objectives We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. Methods We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory’s 99th -percentile upper limit of normal (xULN). Results 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs.

Abstract Background Policy research aims to provide evidence to inform government policy decisions about health and social care. Engaging and involving the public and patients in this work is widely recognised as essential. Research funders prioritise equality, diversity and inclusion (EDI) in patient and public involvement and engagement (PPIE), but people who are most likely to experience poor outcomes are also those least likely to be involved in research. This paper describes our experience of setting out to understand how to overcome barriers to EDI in PPIE in the research carried out by the National Institute for Health and Care Research (NIHR) Policy Research Unit in Maternal and Neonatal Health and Care (PRU-MNHC), in a PPIE consultation project we called The Listening Series. Methods We convened five video-recorded online discussion groups involving 20 individuals advocating for groups who are under-represented in our research. Those taking part included people working with Black and Asian women and families, young parents, those from socially deprived backgrounds, and women and families with physical and learning disabilities. Discussions focussed on practical solutions to addressing challenges to people being excluded, and how to improve EDI in our research. Learning and reflection Five key themes were identified: ‘build trust’; ‘involve us from the beginning’; ‘show us impact’; ‘use clear, appropriate and inclusive communication’; and ‘imagine life in our shoes’. We used the learning to create a guidance document for researchers and an accompanying 15-minute film. We also took practical steps to embed the learning strategically by expanding our Task Group for PPIE in the PRU-MNHC to include four Listening Series invitees with a remit to champion EDI in our research and ensure that it is embedded in our PPIE activities. We continue to reflect on and work to address the associated challenges. Conclusions The Listening Series helped us rethink our processes for inclusion to go beyond traditional methods of involvement and engagement. The themes identified pose challenges that require time, resource and empathic engagement from researchers to be meaningfully resolved. This has implications for policy makers and research funders who need to consider this in their processes.

BACKGROUND. Bariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1-3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin. METHODS. To identify mediators of disordered metabolism in PBH, we analyzed the plasma metabolome in the fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-Roux-en-Y gastric bypass (post- RYGB) (n = 10), and nonsurgical controls (n = 8). RESULTS. In the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone [beta]-hydroxybutyrate were increased by 30%-80% in PBH versus asymptomatic. Conversely, multiple amino acids (branched-chain amino acids, tryptophan) and polyunsaturated lipids were reduced by 20%-50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced 2- to 10-fold in PBH in the fasting state. Postprandially, plasma serotonin was uniquely increased 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin. CONCLUSION. Together these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target. FUNDING. National Institutes of Health (NIH) grant R01-DK121995, NIH grant P30-DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo grant 2018/22111-2., Introduction Bariatric and upper gastrointestinal surgery exerts profound improvements in glucose metabolism and can even induce remission of type 2 diabetes (T2D) (1, 2), thus demonstrating the importance of the [...]

BackgroundInadequate water, sanitation and hygiene (WASH) in health facilities, and the low adherence to infection control protocols can increase the risk of hospital-acquired (nosocomial) infections (HAIs). The risk for HAIs can increase morbidity, and mortality, health care cost, but also contribute to increased microbial resistance.ObjectivesThe study aimed to assess WASH facilities and practices, and levels of nosocomial pathogens in selected health facilities in Oromia Region and Southern, Nations and Nationalities and Peoples (SNNPs) Region.Materials and methodsAn observational cross-sectional study design was employed to assess the WASH facilities in health care in SNNPs (Bulle and Doyogena) and Oromia (Bidre) regions through interviews and direct observations (n = 26 facilities). Water and surface samples were collected from major hospitals and health centers. A total of 90 surface swabs and 14 water samples were collected identified, characterized and tested for antimicrobial susceptibility. Epi-info was used for data entry and the data was subsequently exported to Stata version 17 for data cleaning and analysis.ResultsWater supply, toilet facilities, and waste management procedures were suboptimal (below the minimum standards of WHO). Only 11/26 of the health facilities had access to water at the time of the survey. The lowest hand-hygiene compliance was for Bidre (4%), followed by Doyogena (14%), and Bulle (36%). Over 70% of the identified bacteria were from four categories: Staphylococcus spp., Bacillus spp., E. coli, and Klebsiella spp. These bacteria also found in high-risk locations including neonatal intensive care units, delivery and surgical rooms. Antimicrobial susceptibility detected in ≥50% of the isolates for penicillin, cefazolin, ampicillin, oxacillin, and cotrimoxazole, and ≥ 50% of the isolates displayed multi-drug resistance.ConclusionInvesting in WASH infrastructures, promotion of handwashing practices, implementing infection prevention and control (IPC) measures and antibiotic stewardship is critical to ensure quality care in these settings. We recommend careful use of higher generation cephalosporins and fluoroquinolones.

Objectives: Obesity, diabetes and high-calorie diets are associated with defective sperm function and lowered male fertility. Mature spermatozoa primarily use fructose and glucose, and glucose and glycerol metabolism are important for sperm function. We recently discovered a novel mammalian enzyme, glycerol-3-phosphate (Gro3P) phosphatase (G3PP), and showed that it operates the glycerol shunt by hydrolyzing Gro3P to glycerol, and regulates glucose, lipid and energy metabolism in pancreatic β-cells and liver. We now observed that G3PP expression is the highest in the testis and spermatozoa, and investigated its role in male fertility. Methods: We examined G3PP expression during spermatogenesis in mouse and assessed male fertility and spermatozoon function in conditional germ cell specific G3PP-KO (cG3PP-KO) mice and tamoxifen-inducible conditional germ cell G3PP-KO (icG3PP-KO) mice. We also determined the structural and metabolic parameters and oxidative stress in the spermatozoa from icG3PP-KO and control mice. Results: G3PP expression in mouse spermatocytes and spermatids markedly increases during spermatogenesis. Male cG3PP-KO mice, in which germ cell G3PP is deleted from embryonic stage, are infertile due to dysfunctional sperm with reduced motility and capacitation, and elevated spontaneous acrosomal reaction and oxidative stress. However, icG3PP-KO male mice do not have altered fertility, due to the presence of ∼10% normal spermatozoa. icG3PP-KO spermatozoa display significantly reduced functionality and morphological and ultrastructural alterations. The icG3PP-KO spermatozoa show reduced glycerol production, elevated levels of Gro3P and reactive oxygen species (ROS), and oxidative stress that is associated with increased mitochondrial membrane potential. Conclusions: Germ cell G3PP deletion leads to the generation of spermatozoa that are functionally and structurally abnormal, likely due to the build-up of Gro3P that increases mitochondrial membrane potential, ROS, and oxidative stress and alters spermatozoa function. Overall, the results indicate that G3PP and the glycerol shunt are essential for normal spermatozoa function and male fertility.

The hospitality industry stands at the cusp of a revolutionary transformation spurred by the advent of Artificial Intelligence (AI). This paper explores the challenges and opportunities associated with AI integration in an arena historically reliant on the nuances of the human touch. The research illuminates the potential for AI to redefine facets of the hospitality experience, from augmenting customer interactions to refining service delivery and catalysing economic growth. It examines the potential for AI to infuse the hospitality industry with unprecedented levels of efficiency and personalised service while also addressing the complexities introduced by this digital evolution. The pivot towards AI is not without its impediments. Technological constraints, such as the significant investment required for the deployment of AI and the compatibility with existing systems, pose substantial barriers. Cultural resistance emerges from a workforce accustomed to traditional service norms, and ethical dilemmas surface over customer data use and machine-based interactions' impersonal nature. This research delineates these impediments, offering a panoramic view of the intricate dynamics. In dissecting the nuances of AI adoption, the study first harnesses a comprehensive literature review to pinpoint the pivotal factors at play. These variables are then intricately modelled through Total Interpretive Structural Modeling (TISM) analysis, which unravels the interdependencies and assigns a hierarchy based on driving and dependence power. This modelling facilitates a structured understanding of the challenges, setting the stage for strategic intervention. Validation of the TISM model ensues through MICMAC analysis, further refining the categorisation of factors by their level of influence. This dual-analytical paradigm affords a granular perspective on the factors that govern AI adoption, laying the groundwork for strategic solutions that are both nuanced and actionable. The results of the analyses reveal that while AI possesses the potential to disrupt the hospitality sector positively, its implementation requires a subtle approach that mitigates the identified challenges. In the wake of this analytical journey, the paper culminates with strategic recommendations designed to steer industry stakeholders through the AI adoption process. These recommendations stress the importance of a balanced approach that harnesses the strengths of AI to complement and enhance the human elements intrinsic to hospitality. This includes investing in employee training to work alongside AI tools, adopting transparent data practices to maintain customer trust, and fostering an organisational culture that embraces technological innovation while valuing human engagement.

يهدف البحث إلى التعرف على الذكاء الاصطناعي بشكل عام، وضوابط استخدامه، ثم التعرف على مدى قدرته على خدمة الباحث الشرعي عند إنجاز أبحاثه في الإجابة عن الأسئلة المتعلقة بالثقافة الإسلامية والعلوم الشرعية، في سبيل الترقي بعمل الذكاء الاصطناعي من خلال التعاون المكثف بين المبرمجين من جهة وعلماء الشريعة من جهة أخرى، ولقد قام البحث على المنهج: الوصفي من خلال طرح أسئلة نوعية على الذكاء الاصطناعي في الثقافة الإسلامية، والتفسير والحديث والفقه، وتم تقسيم البحث إلى مقدمة ومبحثين، المبحث الأول: تعريف تقنية الذكاء الاصطناعي وأهميته في التعليم. المبحث الثاني: مدى إمكانية الذكاء الاصطناعي على تقديم الإجابات الصحيحة عن الأسئلة الشرعية. وخلص البحث إلى أن الذكاء الاصطناعي لا يزال قاصرًا عن تقديم إجابات نوعية للباحث الشرعي، وعليه يقع على عاتق العلماء اليوم العمل على تطوير الذكاء الاصطناعي لخدمة العلوم الشرعية.

BackgroundNumerous studies have linked mitochondrial dysfunction to the development of type 2 diabetes (T2D) by affecting glucose-stimulated insulin secretion in pancreatic beta cells and reducing oxidative phosphorylation in insulin-responsive tissues. Given the strong genetic underpinnings of T2D, research has explored the connection between mitochondrial DNA haplogroups, specific variants, and the risk and comorbidities of T2D. For example, haplogroups F, D, M9, and N9a have been linked to an elevated risk of T2D across various populations. Additionally, specific mitochondrial DNA variants, such as the rare mtDNA 3243 A>G and the more prevalent mtDNA 16189 T>C, have also been implicated in heightened T2D risk. Notably, these associations vary among different populations. Given the high incidence of T2D in the Gulf Cooperation Council countries, this study investigates the correlation between T2D and mitochondrial haplogroups and variants in Arab populations from the Gulf region.MethodsThis analysis involved mitochondrial haplogroup and variant testing in a cohort of 1,112 native Kuwaiti and Qatari individuals, comprising 685 T2D patients and 427 controls. Complete mitochondrial genomes were derived from whole exome sequencing data to examine the associations between T2D and haplogroups and mitochondrial DNA variants.ResultsThe analysis revealed a significant protective effect of haplogroup H against T2D (odds ratio [OR] = 0.65; P = 0.022). This protective association persisted when adjusted for age, sex, body mass index (BMI) and population group, with an OR of 0.607 (P = 0.021). Furthermore, specific mitochondrial variants showed significant associations with T2D risk after adjustment for relevant covariates, and some variants were exclusively found in T2D patients.ConclusionOur findings confirm that the maternal haplogroup H, previously identified as protective against obesity in Kuwaiti Arabs, also serves as a protective factor against T2D in Arabs from the Gulf region. The study also identifies mitochondrial DNA variants that either increase or decrease the risk of T2D, underscoring their role in cellular energy metabolism.

IntroductionFamilial hypercholesterolemia, the highly prevalent form of dyslipidemia, is a well-known risk factor for premature heart disease and stroke worldwide. Statins, which inhibit 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the first-choice treatment for dyslipidemias, and have been effective in reducing the risk of stroke and myocardial infarction. However, emerging evidence indicates that statins may increase the incidence of new-onset type 2 diabetes by reducing β-cell mass and function. Notably, past in vitro reports studying the effects of statins on β-cells were performed without including free fatty acids in the model. This factor should have been addressed since these agents are used to treat individuals with hyperlipidemia.MethodsHere, we used a mouse insulinoma MIN6 β-cell culture model to assess the efficacy, cytotoxicity, and insulin-suppressive effects of simvastatin and pravastatin in the presence of palmitic, linoleic, and oleic acids cocktail to mimic mixed lipids challenge in a biologically relevant setting.Results and discussionOur findings indicate that simvastatin was more effective in lowering intracellular cholesterol but was more cytotoxic as compared to pravastatin. Similarly, simvastatin exhibited a higher suppression of total insulin content and insulin secretion. Both drugs suppressed insulin secretion in phases 1 and 2, dose-dependently. No significant effect was observed on mitochondrial respiration. More importantly, elution experiments showed that insulin content diminution by simvastatin treatment was reversible, while exogenous mevalonate did not improve total insulin content. This suggests that simvastatin's influence on insulin content is independent of its specific inhibitory action on HMG-CoA reductase. In conclusion, our study identified that simvastatin was more effective in lowering intracellular cholesterol, albeit it was more toxic and suppressive of β-cells function. Notably, this suppression was found to be reversible.

BackgroundDengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2.ObjectiveThis study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses.MethodsThe chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses.ResultsAmong these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski’s “rule of 5”, showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin.ConclusionTaken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.

BackgroundThe Kuwaiti and Qatari populations have a high prevalence of obesity, a major risk factor for various metabolic disorders. Previous studies have independently explored mitochondrial DNA (mtDNA) variations and their association with obesity in these populations. This study aims to investigate the role of mtDNA haplogroups and variants in obesity risk among these Gulf populations.MethodsWhole exome sequencing data from 1,112 participants (348 Kuwaitis and 764 Qataris) were analyzed for mtDNA variants. Participants were classified as obese or non-obese based on body mass index (BMI). Association analyses were performed to examine the relationship between mtDNA haplogroups and obesity, adjusting for covariates such as age and sex.ResultsHaplogroup R was found to be protective against obesity, with an odds ratio (OR) of 0.69 (p = 0.045). This association remained significant after adjusting for age and sex (OR = 0.694; 95% CI: 0.482-0.997; p = 0.048). Several mtDNA variants, particularly those involved in mitochondrial energy metabolism, showed nominal associations with obesity, but these did not remain significant after correcting for multiple testing.ConclusionHaplogroup R consistently demonstrates a protective association against obesity in both Kuwaiti and Qatari populations, highlighting its potential as a biomarker for obesity risk in the Gulf region. However, further research with larger sample sizes is needed to validate these findings and clarify the role of mtDNA variants in obesity.

IntroductionIncreasing evidence from human and animal model studies indicates the significant role of microRNAs (miRNAs) in pancreatic beta cell function, insulin signaling, immune responses, and pathogenesis of type 1 diabetes (T1D).MethodsWe aimed, using next-generation sequencing, to screen miRNAs from peripheral blood mononuclear cells of eight independent Kuwaiti-Arab families with T1D affected siblings, consisting of 18 T1D patients and 18 unaffected members, characterized by no parent-to-child inheritance pattern.ResultsOur analysis revealed 20 miRNAs that are differentially expressed in T1D patients compared with healthy controls. Module-based weighted gene co-expression network analysis prioritized key consensus miRNAs in T1D pathogenesis. These included hsa-miR-320a-3p, hsa-miR-139-3p, hsa-miR-200-3p, hsa-miR-99b-5p and hsa-miR-6808-3p. Functional enrichment analysis of differentially expressed miRNAs indicated that PI3K-AKT is one of the key pathways perturbed in T1D. Gene ontology analysis of hub miRNAs also implicated PI3K-AKT, along with mTOR, MAPK, and interleukin signaling pathways, in T1D. Using quantitative RT-PCR, we validated one of the key predicted miRNA-target gene-transcription factor networks in an extended cohort of children with new-onset T1D positive for islet autoantibodies. Our analysis revealed that hsa-miR-320a-3p and its key targets, including PTEN, AKT1, BCL2, FOXO1 and MYC, are dysregulated in T1D, along with their interacting partners namely BLIMP3, GSK3B, CAV1, CXCL3, TGFB, and IL10. Receiver Operating Characteristic analysis highlighted the diagnostic potential of hsa-miR-320a-3p, CAV1, GSK3B and MYC for T1D.DiscussionOur study presents a novel link between hsa-miR-320a-3p and T1D, and highlights its key regulatory role in the network of mRNA markers and transcription factors involved in T1D pathogenesis.

Objective: This study explores the frequency of human leukocyte antigen (HLA) genes, particularly HLA-B alleles, within the Kuwaiti population. We aim to identify alleles with known associations to adverse drug reactions (ADRs) based on existing literature. We focus on the HLA-B gene due to its well-documented associations with severe cutaneous adverse reactions and the extensive pharmacogenetic research supporting its clinical relevance.MethodsWe utilized the HLA-HD tool to extract, annotate, and analyse HLA-B alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major HLA-B pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature.ResultsThe distribution of HLA-B alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals.ConclusionOur study enriches the regional genetic landscape by delineating HLA-B allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.

Background Reduced estimated glomerular filtration rate (eGFR) is associated with lower use of invasive management and increased mortality after acute coronary syndrome (ACS). The reasons for this are unclear.Methods A retrospective clinical cohort study was performed using data from the English National Institute for Health Research Health Informatics Collaborative (2010–2017). Multivariable logistic regression was used to investigate whether eGFR

The study proposed the removal of Brilliant Green, a cationic dye, by adsorption process from wastewater solution utilizing a low-cost adsorbent such as Nutraceutical Industrial Pepper Seed Spent (NIPSS). The study comprises an investigation of the parametric influence on the adsorption process. The parameters identified are pH, dye concentration, process temperature, quantity of the adsorbent, and particle size. The study of statistics found from experiments was carried out by incorporating Freundlich, Brouers-Sotolongo, Langmuir, Toth, Sips, Jovanovic, and Redlich-Peterson isotherm models. The adsorption kinetics were determined by implementing pseudo-first-order and second-order models, diffusion film models, and Dumwald-Wagner and Weber-Morris models. The experimental adsorption capacity qe was found to be about 130 mg/g. This value was closest to the maximum adsorption of 144.6mg/g predicted by the Brouers-Sotolongo isotherm which had a correlation coefficient (R2) of 0.998. The adsorption kinetics data was confirmed to be a pseudo-second-order model. The change in free energy, enthalpy change, and entropy change were vital thermodynamic factors in concluding that adsorption is almost spontaneous and endothermic process. Change in enthalpy (ΔH°) reduced value indicates the physical nature of the process. The adsorption of BG dye on the adsorbent surface was authenticated by FTIR spectroscopy and SEM imaging. A Central Composite Design (CCD) Quadratic model under Response Surface Methodology (RSM) was implemented for statistical optimization of adsorption capacity for the five parameters studied, namely, time, temperature, concentration of the dye, weight of the adsorbent, and pH. Software Design Expert 7.0 was used to evaluate 3D contour plots. The process of optimization yielded a value of 350 mg/g. Thus, incrementing the adsorption process by 84.2 %. The study provides insights on various dye and adsorbent interaction possibilities and derives that NIPSS is an efficient adsorbent to extract BG dye from wastewater solutions.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (