IntroductionExposure to waterpipe smoke (WPS) in humans and experimental animals has been reported to cause oxidative stress and thrombotic complications. L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione (GSH) in tissues. Nevertheless, the possible mitigating effects of OTC on platelet aggregation induced by WPS inhalation, and its underlying mechanisms of action remain unexplored. This is the goal of the present work in BALB/c mice. Methods Animals were exposed to either WPS or air (control) by inhalation daily for 30 min for 1 month. OTC was given 1 h before each exposure session by gavage at a dose of 80 mg/kg. Results WPS inhalation increased various markers of platelet aggregation, coagulation, fibrinolysis and endothelial integrity (platelet factor 4, tissue factor, fibrinogen, thrombin-antithrombin complexes, plasminogen activator inhibitor, P-selectin, E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1). It also shortened the prothrombin time and partial thromboplastin time and augmented the plasma concentrations of C-reactive protein and triglycerides. All these effects were attenuated by OTC treatment. Likewise, OTC administration significantly mitigated platelet aggregation in vivo. Platelets isolated from mice exposed to WPS showed high levels of markers of oxidative and nitrosative stress, calcium, annexin V and calpain. The latter effects were significantly alleviated by OTC treatment. Discussion Our data show that OTC administration significantly mitigated WPS-induced in vivo endothelial injury and thrombotic events, as well as platelet oxidative stress and apoptosis. This finding provides evidence on the mechanisms of toxicity of WPS on platelet physiology, and the alleviative action of OTC.

Vitamin D deficiency is a widespread global health issue, even in sun-rich regions like the United Arab Emirates (UAE), where environmental, behavioral, and cultural factors limit skin exposure to ultraviolet B (UVB) radiation. To address this, we developed and assessed a sensor-guided indoor sunlight reflection system that redirects natural sunlight indoors for controlled vitamin D synthesis. Sixteen healthy adults participated in a pre-post interventional study using this system, which features automated solar tracking and UV-index-based exposure control. Participants underwent four sessions weekly for eight weeks, each lasting 10–20 min depending on skin tone and UV intensity. Serum samples were taken at the start, middle, and end of the study. We measured eight vitamin D metabolites and epimers with a high-specificity LC-MS/MS workflow that differentiates 25(OH)D2/D3 and C-3 epimers. The intervention was associated with significant, time-dependent increases in serum 25(OH)D3, total 25-hydroxyvitamin D, and 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] (p < 0.001 for all), with large effect sizes (partial η² = 0.35–0.44). Mean 25(OH)D3 increased from 1.99 to 4.11 ng/mL (+ 106%), total 25(OH)D from 5.0 to 7.7 ng/mL (+ 54%), and 1α 25(OH)2D3 from 0.33 to 0.74 ng/mL (+ 124%). Meanwhile, 25(OH)D2 and its epimer decreased slightly (-28% and − 30%), supporting endogenous D3 production from sunlight. No changes in 7α-hydroxycholesten-3-one (7αC4) suggested stable hepatic cholesterol breakdown. Throughout the study, no adverse events or safety issues occurred. Controlled indoor exposure to full-spectrum sunlight was associated with increased dermal vitamin D3 synthesis, providing physiological effects comparable to outdoor sunlight exposure without heat or overexposure risks. This study suggests that sensor-guided indoor full-spectrum sunlight exposure is a feasible and well-tolerated approach to improve vitamin D status in populations with limited sun exposure. By integrating optical engineering, biosafety algorithms, and precise analytics, this approach offers a potentially sustainable strategy for addressing vitamin D deficiency in indoor-living populations.

BACKGROUND:Obstructive sleep apnea (OSA)-related intermittent hypoxemia may contribute to renal endothelial injury. Evidence on urinary immunoglobulin M (IgM-uria) in OSA is limited. We evaluated associations between OSA severity and IgM-uria and albuminuria in non-diabetic and diabetic patients. METHODS:Cross-sectional study of 124 adults undergoing overnight polysomnography at a tertiary sleep clinic. Morning urine IgM and albumin were measured and normalized to creatinine. Multivariable linear regression models adjusted for age, sex, smoking, body mass index, and hypertension were fitted and interactions with diabetes status were tested. RESULTS:Among non-diabetic participants (n = 98), a 1 SD decrease in mean SpO2 was associated with a 0.65 SD increase in urinary IgM-uria and a 0.50 SD increase in albuminuria (both p < 0.001). A 1 SD increase in oxygen desaturation index was associated with 0.29 SD and 0.33 SD increases in IgM-uria (p = 0.014) and albuminuria (p = 0.006), respectively. A 1 SD increase in apnea-hypopnea index was associated with 0.24 SD and 0.22 SD increases in IgM-uria (p = 0.034) and albuminuria (p = 0.043), respectively. These associations were not significant among patients with diabetes (n = 26). CONCLUSIONS:Urinary IgM and albumin were associated with OSA severity in non-diabetic individuals, suggesting they could serve as inexpensive, non-invasive biomarkers of glomerular injury in sleep apnea. Longitudinal studies are warranted to assess reversibility with OSA treatment.

PURPOSE:Down syndrome (DS) is associated with metabolic dysregulation, obesity, and increased risk of chronic inflammation. This study aimed to assess subclinical inflammation in children with DS by evaluating inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), and their association with metabolic parameters including ghrelin, lipid profiles, and vitamin D levels. METHODS:A total of 49 children with DS (aged 1-18 years) and 22 age-matched healthy controls were enrolled. Anthropometric data, body fat percentage, and metabolic parameters were assessed. Inflammatory markers (hs-CRP, apolipoprotein-B [Apo B], adiponectin), metabolic hormones (ghrelin, insulin), and lipid profiles were determined from venous blood samples. Statistical analyses included bivariate correlation, analysis of variance, and multiple linear regression to identify predictors of inflammation. RESULTS:Children with DS exhibited significantly higher hs-CRP levels than controls (p=0.03), indicative of increased systemic inflammation. Higher hs-CRP levels were associated with older age (r=0.33, p=0.006), greater obesity (body mass index: r=0.32, p=0.011), and elevated serum insulin and low-density lipoprotein levels. Ghrelin levels correlated negatively with Apo B (r=-0.41, p&lt;0.001) and positively with hs-CRP (r=0.30, p=0.012). Predictors of inflammation (based on hs-CRP) included older age, male sex, higher gamma-glutamyl transferase level, and a diagnosis of DS (adjusted R²=0.276). CONCLUSION:Children with DS are prone to metabolic inflammation, with increasing age and obesity exacerbating inflammatory responses. Clinicians should monitor and manage weight, dyslipidemia, and inflammation in this population to prevent long-term complications such as cardiovascular diseases and insulin resistance.

IntroductionObesity-related type 2 diabetes (DM) is increasing rapidly and at present reaching epidemic proportions in some Worldwide populations. The aim of this study was to provide new knowledge on the interplay between genetic and lifestyle obesity-related risk factors in populations with the highest incidence of obesity-related diabetes could provide an important tool to help prevent or delay diabetes onset in high-risk groups.MethodsCommunity free-living individuals visiting primary health centers were recruited to the study following informed written consent. Demographic and clinical characteristics, physical activity, dietary intake and biological markers of DM were measured at baseline and follow up. Validated questionnaires were used to assess physical activity and dietary intakes. A Cox proportional hazards analysis was used to examine the risk of developing diabetes diagnosed using the WHO cut-of-points criterion of HbA1c ≥ 6.5% at follow after adjusting for known clinical risk indicators.ResultsA total of 375 Community free-living locals UAE citizens subjects, 348 (93%) of them females and 253 non-locals’ expatriates [187 (73%)] females were recruited and followed up for a period of 427 ± 223 days. Using WHO cut-of-points for diagnosing DM (HbA1c ≥ 6.5%), 31 (6%) subjects out of 545 followed up developed DM. Overall local United Arab Emirates (UAE) citizens reported significantly lower levels of physical activity in comparison to non-local expatriates. The Cox proportional hazard model analysis revealed that being obese, UAE national and physically inactive is associated with a significantly increased risk of DM after adjusting for other prognostic indicators [non-UAE national: Odd ratio (95% CI): 0.13 (0.04, 0.47); p=0.002; physically active: 0.31 (0.11, 0.90); p=0.002]. The Kaplan Meier figures show the significantly increased risk of developing DM in physically inactive local UAE citizens compared with expatriates’ residents (p<0.05). In contrast risk of developing DM was no different between physically very active UAE nationals compared to non-nationals at follow up (P>0.5).ConclusionOur finding suggests that physical inactivity in high-risk groups is the most important risk factor for developing DM. Urgent actions are needed to increase physical activity in this high-risk group coupled with further research to understand the reasons for this striking indigenous population variability.

Aims:The precise differentiation between Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) can be challenging in clinical practice, particularly in adults. We aimed to validate the diagnostic accuracy and performance of urinary C-peptide creatinine ratio (UCPCR) for distinguishing T1DM from T2DM in the Emirati population. Methods:This prospective cross-sectional study included 79 patients with diabetes (19 T1DM, 60 T2DM) from Tawam Hospital Diabetes Center, UAE. Post-prandial urine samples were collected for UCPCR measurement using chemiluminescent immunoassay. Receiver operating characteristic (ROC) analysis determined optimal cut-offs. Multivariable logistic regression and cost-comparison analyses were performed. Results:Mean UCPCR was significantly lower in T1DM compared to T2DM (0.29 ± 0.64 vs 1.44 ± 1.82 nmol/mmol, p<0.001). ROC analysis revealed that a UCPCR cut-off of <0.25 nmol/mmol achieved 100% sensitivity and 91.7% specificity for T1DM diagnosis (AUC 0.991, 95% CI: 0.978-1.000). In patients with diabetes duration <5 years, UCPCR maintained excellent discrimination (AUC 0.988, sensitivity 100%, specificity 91.7%). However, specificity declined in patients with a diabetes duration of >10 years (82.4%), with 15% of these longstanding T2DM patients exhibiting UCPCR values <0.25 nmol/mmol, reflecting progressive beta-cell decline. Multivariable regression identified UCPCR (OR 0.001; 95% CI: 0.000-0.012; p<0.001) as the strongest independent predictor of T1DM. Cost-comparison analysis demonstrated ≥ 90% cost reduction when compared with serum C-peptide or autoantibody panels. Conclusions:UCPCR < 0.25 nmol/mmol accurately identifies T1DM in the Emirati population. This cost-effective, non-invasive test could improve clinical practice through enhanced diagnostic accuracy and reduced healthcare costs.

Introduction:The coronavirus disease 2019 (COVID-19) pandemic resulted in significant global mortality and morbidity, with emerging mutant strains continuing to potentially precipitate severe respiratory illness. Two clinical assessment tools, namely, the COVID-19 Risk of Complications Score (CRS), based on 13 comorbidities, and the ALKA (age, lactate dehydrogenase, kidney function, and albumin) score have been developed to predict disease severity among patients who are symptomatic at presentation. This study aimed to compare the performance of these two risk-scoring systems in predicting hospital admission, critical illness, and mortality. Methods:This retrospective study included 368 patients diagnosed with COVID-19 at SEHA hospitals in Al Ain over a six-month period. The CRS and ALKA scores were calculated to predict hospital admission, critical illness, and mortality. Predictive ability was assessed using receiver operating characteristic (ROC) curve analysis. Odds ratios (ORs) were calculated to assess the risk of hospital admission, critical illness, and mortality. Results:The mean age of the patients was 51 ± 19.42 years, and 145 (39.4%) of them were male. Among the patients, 162 required inpatient care, 13 required invasive ventilation, and the mortality rate was 4.9% (eight patients). ROC analysis revealed that ALKA outperformed CRS in predicting hospital admission (ALKA area under the curve [AUC] 0.79 vs. CRS AUC 0.71), critical illness (ALKA AUC 0.76 vs. CRS AUC 0.67), and mortality (ALKA AUC 0.96 vs. CRS AUC 0.82). The OR for ALKA outperformed CRS in predicting hospital admission (ALKA 3.12 vs. CRS 1.12), critical illness (ALKA 2.9 vs. CRS 2.01), and mortality (ALKA 6.25 vs. CRS 1.1). Conclusion:Our study demonstrated that ALKA score outperforms CRS in predicting hospital admission, critical illness, and mortality among patients with symptomatic COVID-19 at initial presentation. Further external validation of both tools is required to assess their effectiveness in different healthcare settings.

Background/Objectives: Water-soluble vitamins are essential micronutrients requiring regular dietary replenishment due to minimal body storage capacity. Medical students.; despite their health knowledge, may be at risk for subclinical deficiencies due to academic stress and life-style factors. This study assessed water-soluble vitamin status to evaluate screening needs in this educated population. Methods: A cross-sectional study was conducted among 91 healthy medical students (age 18–23 years) at UAE University from September 2023 to January 2024. Serum levels of folate (B9), cobalamin (B12), and ascorbic acid (Vitamin C) were measured using validated high-performance chemiluminescent immunoassays. Demographic, anthropometric, dietary, and lifestyle data were collected via structured questionnaires. Statistical analyses included multivariate logistic regres-sion, correlation analyses, and receiver operating characteristic (ROC) curves. Results: Among the participants (70.3% female; mean age 19.8 ± 1.4 years; BMI 23.2 ± 2.9 kg/m2), vita-min C showed the highest prevalence of suboptimal levels at 7.7% (7/91 participants), comprising 2.2% with deficiency (<28 µmol/L, n = 2) and 5.5% with insufficiency (28–40 µmol/L, n = 5). Mean vitamin C was 56.7 ± 14.8 µmol/L. Vitamin B12 insufficiency (200–300 pg/mL) affected 9.0% (8/89) of students, with a mean of 485.3 ± 165.0 pg/mL. A non-significant trend toward higher insufficiency rates was observed among female students. No deficiencies were observed for folate (mean 14.1 ± 4.9 ng/mL). Multivariate analysis identified low fruit/vegetable intake (OR 4.8; 95% CI: 1.3–17.6; p = 0.018); high stress scores (OR 3.2; 95% CI: 1.1–9.4; p = 0.033); and female gender (OR 2.9; 95% CI: 0.9–9.1; p = 0.071) as predictors of suboptimal vitamin C. Vitamin C levels correlated positively with dietary quality (r = 0.412; p < 0.001) and negatively with stress scores (r = −0.241; p = 0.031). Despite being a health-educated population, nearly 10% of medical students demonstrated suboptimal water-soluble vitamin levels, particularly vitamins C and B12. Conclusions: These findings support implementing targeted screening programs focusing on high-risk groups, including students with poor dietary habits, high stress levels, or specific gender-based risks.

Background:An early and accurate diagnosis of sepsis is critical for improving patient outcomes. Extended inflammation parameters (EIPs), derived from routine complete blood count (CBC) analysis, have emerged as promising biomarkers for inflammatory response. This study aimed to explore the diagnostic potential of a model combining several EIPs for identifying sepsis in a case-control setting. Participants and methods:A retrospective, single-center, case-control study was conducted at Tawam Hospital, AlAin, United Arab Emirates involving 157 participants; 53 patients with confirmed sepsis per Sepsis-3 criteria admitted to the Intensive Care Unit (ICU) and 104 control participants from outpatient clinics with no obvious evidence of infection. EIPs, including immature granulocyte count (IG#), neutrophil reactivity intensity (NEUT-RI), and reactive lymphocyte percentage per lymphocyte (RE-LYMP%/L), were retrieved from initial CBCs performed on a Sysmex XN-1000 analyzer. A three-parameter logarithmic model was developed, and its performance was assessed using receiver operating characteristic (ROC) curve analysis. Internal validation was performed using 1,000 bootstrap iterations to estimate bias-corrected performance. Results:The logarithmic model, i.e., log(IG# + 1) + log(NEUT-RI/100 + 1) + log(RE-LYMP%/L/50 + 1), combining IG#, NEUT-RI, and RE-LYMP%/L demonstrated high apparent discrimination for identifying sepsis, with an Area Under the Curve (AUC) of 0.941 (95% CI: 0.902-0.980), a sensitivity of 88.5% (95% CI: 77.0-95.8%), and a specificity of 91.3% (95% CI: 84.2-96.0%). Bootstrap internal validation yielded an optimism-corrected AUC of 0.923 (95% CI: 0.874-0.966), with minimal optimism (0.018), suggesting model stability within this dataset. Conclusion:A prediction model combining three different EIPs demonstrated high discrimination in a case-control setting, however this design of comparing ICU sepsis patients to healthy outpatient controls introduces severe spectrum bias characteristic of two-gate studies, which can inflate discrimination metrics significantly when compared with single-gate Emergency Department populations where diagnostic uncertainty is genuine. These results should be considered preliminary exploratory findings only. The extreme spectrum bias inherent to our case-control design means reported performance reflects statistical discrimination in an artificial scenario rather than real-world diagnostic accuracy, with expected ED performance substantially lower (estimated AUC 0.70-0.79). Rigorous prospective validation in consecutive ED patients with suspected infection, including head-to-head comparison with established biomarkers procalcitonin and C-reactive protein, is essential before any clinical consideration.

BackgroundVitamin C supplementation may enhance the absorption of levothyroxine in patients with hypothyroidism. This proof-of-concept pilot study aimed to assess the frequency of vitamin C insufficiency and evaluate the feasibility and potential therapeutic signal of vitamin C supplementation in patients requiring high-dose levothyroxine.MethodsThis two-phase study initially assessed vitamin C levels in 26 hypothyroid patients and 91 healthy controls. In phase two, a double-blind, randomized, placebo-controlled trial was conducted. Twelve patients were randomized, and 11 completed the study. Participants received either 1g daily vitamin C (n=6) or a near-matched pH placebo (n=5) for 16 weeks. Primary outcomes were changes in the Zulewski clinical score and thyroid-stimulating hormone (TSH) levels.ResultsVitamin C insufficiency was more frequent in hypothyroid patients (19.2%) versus controls (7.7%), though the difference in mean levels was not statistically significant (59.33 ± 24.62 µmol/L vs 73.12 ± 14.03 μmol/L in controls; p=0.21). In the RCT, the vitamin C group showed greater changes in Zulewski score (mean reduction 5.00 vs 1.40 points; difference 3.60, 95% CI: 1.88 to 5.32) and TSH levels (mean reduction 4.08 vs 2.35 mU/L; difference 1.73, 95% CI: -2.14 to 5.60) compared to placebo. However, the groups had significant baseline imbalances, notably in BMI (26.6 vs 43.4 kg/m²). After ANCOVA adjustment for baseline values, the between-group difference remained statistically significant for the Zulewski score (adjusted p=0.004) and marginally significant TSH (adjusted p=0.043). Primary biochemical outcome in this study was TSH rather than direct thyroid hormone measurement, as TSH represents the most sensitive biomarker for thyroid hormone adequacy in primary hypothyroidism and serves as the established therapeutic target in clinical guidelines.ConclusionsThis proof-of-concept study demonstrates the feasibility of studying vitamin C supplementation in patients on high-dose levothyroxine and detects a therapeutic signal, particularly in clinical symptoms. However, the findings are limited by the very small sample size and severe baseline imbalances, precluding any conclusions on efficacy. These preliminary data justify the need for larger, well-controlled trials with stratified randomization to determine if this intervention translates into a clinically meaningful effect.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT05733078, identifier NCT05733078.

Introduction:Anti-thyroid peroxidase antibodies (TPO-Ab) are detectable in almost all patients with autoimmune thyroid disease or Hashimoto's thyroiditis (HT) but may also be present in healthy individuals. HT affects women to a greater extent than men and can lead to overt hypothyroidism, which may increase the risk of miscarriage. There are no local data available on the prevalence of TPO-Ab among healthy women in the United Arab Emirates. The objective of this study was to determine the prevalence of TPO-Ab and assess thyroid function in healthy medical students. Methods:This cross-sectional study used convenience sampling to recruit participants without any history of medical illness or prescribed medications from the College of Medicine at United Arab Emirates University, after obtaining informed consent. Routine demographic, anthropometric, and biochemical data-including TPO-Ab and thyroid-stimulating hormone (TSH) levels-were collected. The normal reference ranges for TPO-Ab and TSH (according to kit-specific recommendations) were 0-34 IU/mL and 0.27-4.20 mIU/L, respectively. Results:A total of 90 healthy participants were enrolled (mean age: 19.83 ± 1.41 years), and all completed blood testing. All male participants (n = 27) had normal TPO-Ab levels, whereas eight female participants (12.7%; n = 63) had elevated TPO-Ab levels (mean: 40.03 ± 102.00 IU/mL). Three female participants (4.5%, n = 63) had elevated TSH levels without any clinical symptoms. Conclusion:Elevated TPO-Ab levels were observed in 12.7% (95% CI: 5.7%-23.5%) of young female participants. These preliminary findings suggest the need for larger prospective studies to evaluate the clinical significance of elevated TPO-Ab and possible related complications.

Background: The prevalence of obesity and related complications is increasing relentlessly worldwide. The effect of intentional weight loss strategies for obese individuals on fat-free muscle mass (FFMM) and metabolic and general health is not well known. The aim of this research is to measure the effects of dietary intake and physical activity level on FFMM change during intentional weight loss in obese subjects. Materials and Methods: Nine hundred and sixty-five overweight and obese community free-living subjects had the effects of physical activity level and dietary intake on FFMM change during intentional weight loss assessed in a prospective longitudinal study. Anthropometric, physical activity, dietary intake, inflammatory markers, and oxidative damage were assessed at baseline and follow-up. Validated questionnaires were used to measure dietary intake and physical activity. We compared FFMM loss or gain between subjects stratified by calorie, protein, and fruit and vegetable intake and physical activity levels. The Cox proportional hazards analysis was used to determine the independent effects of dietary intake and physical activity on FFMM changes. Results: A total of 965 subjects [(mean (SD) age 39 ± 12 years, 801 (83%)] females] were assessed at baseline with follow-up for a period of 427 ± 223 days. Using the WHO criteria for body mass index (BMI), 284 (30%) subjects were found to be overweight and 584 (62%) were obese. We found significant correlations between fat–muscle mass ratio (FMR) and inflammatory and oxidative damage markers. After adjusting for important prognostic indicators, age, gender, occupation, physical activity, and fruit and vegetable consumption were found to be significantly associated with FFMM at baseline (p < 0.05). We found no statistically significant difference in dietary protein or amino acids intake in subjects who gained FFMM compared to those who lost FFMM both at baseline and follow-up. By contrast, high consumption of fruits and vegetable and increased calorie intake were associated with increased odds of FFMM gain (p < 0.05). Increased physical activity was independently associated with significant FFMM gain after adjusting for other important indicators ([hazard ratio (95% CI): 0.49 (0.25, 0.97); p = 0.039]. Conclusions: Increased physical activity and high calorie, fruit and vegetable intake are associated with FFMM preservation or gains during intentional weight loss in obese subjects.

Vitamin A plays a critical role in various biological functions, including vision, cellular differentiation, and immune regulation. However, accurately assessing its status, particularly in obese individuals, presents challenges due to potential alterations in metabolism and distribution. This study utilized Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) methodology to precisely measure serum vitamin A concentrations in population of UAE. The methodology's reliability and precision, as demonstrated through validation procedures, underscore its potential utility in clinical settings. Employing the Multiple Reaction Monitoring mode of positive ion electrospray ionization, the LC-MS/MS system achieves a limit of detection (LOD) of 0.48 ng/mL in serum, while adhering to FDA-US regulations for accuracy and compliance. A key aspect of this study was the application of LC-MS/MS to assess vitamin A status in an obese population within UAE. By employing a diverse cohort of 452 Emirati participants, including 277 individuals from a randomized controlled trial who were assessed at baseline and at 6th month, and 175 healthy individuals aged 18-82 assessed at baseline, this study explores the relationship between obesity and vitamin A levels, shedding light on potential implications for health and well-being. It was an observational study based on a new vitamin A method and participants were asked to eat vitamin A rich foods. The robust performance of the LC-MS/MS methodology positions it as a valuable tool for clinical research. By accurately quantifying vitamin A levels in human serum, this methodology opens avenues for advancing our understanding of vitamin A physiology and its implications for health, particularly in obese populations. In summary, this LC-MS/MS methodology presents a potent tool for clinical studies, providing reliable, specific, and robust detection of vitamin A in human serum, thus, opening a new frontier for advancing our understanding of vitamin A related physiology and health in the obese population.

Aims: The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. Main methods: Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. Key findings: Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinchingoff of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-6, and IL-1 beta, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1 alpha along with alterations in the activity of mitochondrial complexes I, II, III and IV. Significance: Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Background: A possible role of vitamin D epimers and metabolites in the measurement and response to treatment of vitamin D has been reported recently. Furthermore, the influence of underlying vitamin D receptor (VDR) genetic polymorphisms which have been linked to diseases such as obesity remains unclear. We therefore aimed to examine the influence of vitamin D3 and calcium supplements on vitamin D epimer and metabolite concentrations in subjects with and those without vitamin D receptor (VDR) gene polymorphisms. Methods: A total of 277 participants who were part of a randomized intervention trial of vitamin D3 and calcium or a placebo for 6 months had clinical and anthropometric assessments. Blood samples were taken for measurements of vitamin D, epimers and metabolites of vitamin D, four vitamin D receptor gene polymorphism SNPs, namely, BsmI, FokI, TaqI, and ApaI, metabolic and inflammatory markers, and related biochemical variables. Repeated-measures analysis of variance was used to assess the between-group difference in cumulative changes in vitamin D epimers and metabolites at 6 months after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Results: Overall, 277 participants, with a mean (±SD) age of 41 ± 12 and 204 (74%) of whom were female, were included in the study. We found no statistically significant differences in vitamin D metabolites or (epimers) between male and females or younger subjects compared to those over 40 years of age except in 7C4 BL (p < 0.05). There was a statistically significant difference in 1,25(OH)2D3 concentrations between subjects with and those without genotypes AG and the allele G SNP2_Taql VDR gene polymorphism. Vitamin D3 concentrations were also significantly lower in subjects with the CC SNP3_Apal gene polymorphism compared to those without the CC SNP3 gene. No statistically significant effects were seen on vitamin D epimers and metabolites concentration in response to supplements before or after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Conclusions: The CC SNP3 gene had statistically significant influence on vitamin D3 levels. Vitamin D and/or calcium supplements, however, had no effects on vitamin D epimer and metabolite concentration before or after adjusting for the presence of the 4 VDR genotypes and alleles.

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.

Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins’ expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (p < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN.

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) has become a major cause of end-stage hepatic disease worldwide requiring liver transplantation, whereas cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally. Development of MASLD and CVD among young adults is understudied. This study aimed to assess CVD risk in healthy young medical university students using lipid-based and body mass index (BMI)-based 30-year Framingham risk scores (FS30) and to evaluate disease burden for asymptomatic patients with MASLD by performing FibroScan.MethodsWe included medical university students aged 18–30 years without any known medical conditions. All participants underwent physical and anthropometric measurements, and completed a questionnaire. Blood samples were collected for the analysis of glycosylated haemoglobin levels, renal and liver function, biomarker analysis to calculate liver fibrosis risk, and subclinical atherosclerosis biomarkers. Liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) values were measured using FibroScan 430 mini to calculate liver fibrosis and steatosis, respectively. FS30 based on body mass index (FS30-BMI) and lipid levels (FS30-Lipid) were also calculated.ResultsOverall, 138 medical students participated in this study after providing informed consent. Using FS30-Lipid and FS30-BMI, CVD risk was identified in two (1.5%; n = 138) and 23 (17.6%; n = 132) individuals, respectively. MASLD fibrosis was identified based on FibroScan LSMs >7.0 kPa in 12 medical students (9.4%, n = 128; 95% CI, 4.7–14.8%). Consumption of coffee and sugary soft drinks were predictive of liver fibrosis. In total, 36 students (28.6%; n = 128) were found to have hepatic steatosis based on FibroScan CAP values >236 dB, and the predictive factors included increased body fat percentage, male sex, and lack of physical activity. Levels of inflammatory biomarkers, such as C-reactive protein and lipids were not elevated in participants with MASLD.DiscussionCVD risk was identified in >17% of young medical students. The frequency of liver fibrosis and steatosis was also high among the participants, indicating that liver damage starts at a relatively early age. Early intervention is needed among young adults via health promotion and lifestyle changes.

Syeda Vilay Zehra Rizvi,1 Syeda Zoha Zehra Rizvi2 1Jinnah Sindh Medical University, Karachi, Pakistan; 2Jinnah Postgraduate Medical Centre, Karachi, PakistanCorrespondence: Syeda Zoha Zehra Rizvi, Email syedazohazehra@gmail.com