Angiopoietin-2 and Angiopoietin-like Proteins with a Prospective Role in Predicting Diabetic Nephropathy.

Angiopoietins are crucial growth factors for maintaining a healthy, functional endothelium. Patients with type 2 diabetes (T2D) exhibit significant levels of angiogenic markers, particularly Angiopoietin-2, which compromises endothelial integrity and is connected to symptoms of endothelial injury and failure. This report examines the levels of circulating angiopoietins in people with T2D and diabetic nephropathy (DN) and explores its link with ANGPTL proteins. We quantified circulating ANGPTL3, ANGPTL4, ANGPTL8, Ang1, and Ang2 in the fasting plasma of 117 Kuwaiti participants, of which 50 had T2D and 67 participants had DN. The Ang2 levels increased with DN (4.34 ± 0.32 ng/mL) compared with T2D (3.42 ± 0.29 ng/mL). This increase correlated with clinical parameters including the albumin-to-creatinine ratio (ACR) (r = 0.244, p = 0.047), eGFR (r = -0.282, p = 0.021), and SBP (r = -0.28, p = 0.024). Furthermore, Ang2 correlated positively to both ANGPTL4 (r = 0.541, p < 0.001) and ANGPTL8 (r = 0.41, p = 0.001). Multiple regression analysis presented elevated ANGPTL8 and ACRs as predictors for Ang2's increase in people with DN. In people with T2D, ANGPTL4 positively predicted an Ang2 increase. The area under the curve (AUC) in receiver operating characteristic (ROC) analysis of the combination of Ang2 and ANGPTL8 was 0.77 with 80.7% specificity. In conclusion, significantly elevated Ang2 in people with DN correlated with clinical markers such as the ACR, eGFR, and SBP, ANGPTL4, and ANGPTL8 levels. Collectively, this study highlights a close association between Ang2 and ANGPTL8 in a population with DN, suggesting them as DN risk predictors.

Ethnic Variations in the Levels of Bone Biomarkers (Osteoprostegerin, Receptor Activator of Nuclear Factor Kappa-Β Ligand and Glycoprotein Non-Metastatic Melanoma Protein B) in People with Type 2 Diabetes.

The global incidence of Type 2 diabetes (T2D) is on the rise, fueled by factors such as obesity, sedentary lifestyles, socio-economic factors, and ethnic backgrounds. T2D is a multifaceted condition often associated with various health complications, including adverse effects on bone health. This study aims to assess key biomarkers linked to bone health and remodeling-Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL), and Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)-among individuals with diabetes while exploring the impact of ethnicity on these biomarkers. A cross-sectional analysis was conducted on a cohort of 2083 individuals from diverse ethnic backgrounds residing in Kuwait. The results indicate significantly elevated levels of these markers in individuals with T2D compared to non-diabetic counterparts, with OPG at 826.47 (405.8) pg/mL, RANKL at 9.25 (17.3) pg/mL, and GPNMB at 21.44 (7) ng/mL versus 653.75 (231.7) pg/mL, 0.21 (9.94) pg/mL, and 18.65 (5) ng/mL in non-diabetic individuals, respectively. Notably, this elevation was consistent across Arab and Asian populations, except for lower levels of RANKL observed in Arabs with T2D. Furthermore, a positive and significant correlation between OPG and GPNMB was observed regardless of ethnicity or diabetes status, with the strongest correlation (r = 0.473, p < 0.001) found among Arab individuals with T2D. Similarly, a positive and significant correlation between GPNMB and RANKL was noted among Asian individuals with T2D (r = 0.401, p = 0.001). Interestingly, a significant inverse correlation was detected between OPG and RANKL in non-diabetic Arab individuals. These findings highlight dysregulation in bone remodeling markers among individuals with T2D and emphasize the importance of considering ethnic variations in T2D-related complications. The performance of further studies is warranted to understand the underlying mechanisms and develop interventions based on ethnicity for personalized treatment approaches.

Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait.

Obesity and Type 2 Diabetes Mellitus (T2DM) are intricate metabolic disorders with a multifactorial etiology, often leading to a spectrum of complications. Recent research has highlighted the impact of these conditions on bone health, with a particular focus on the role of sclerostin (SOST), a protein molecule integral to bone metabolism. Elevated circulating levels of SOST have been observed in patients with T2DM compared to healthy individuals. This study aims to examine the circulating levels of SOST in a multiethnic population living in Kuwait and to elucidate the relationship between SOST levels, obesity, T2DM, and ethnic background. The study is a cross-sectional analysis of a large cohort of 2083 individuals living in Kuwait. The plasma level of SOST was measured using a bone panel multiplex assay. The study found a significant increase in SOST levels in individuals with T2DM (1008.3 pg/mL, IQR-648) compared to non-diabetic individuals (710.6 pg/mL, IQR-479). There was a significant gender difference in median SOST levels, with males exhibiting higher levels than females across various covariates (diabetes, IR, age, weight, and ethnicity). Notably, SOST levels varied significantly with ethnicity: Arabs (677.4 pg/mL, IQR-481.7), South Asians (914.6 pg/mL, IQR-515), and Southeast Asians (695.2 pg/mL, IQR-436.8). Furthermore, SOST levels showed a significant positive correlation with gender, age, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, insulin, total cholesterol, triglycerides, HDL, LDL, ALT, and AST (p-Value ≥0.05). South Asian participants, who exhibited the highest SOST levels, demonstrated the most pronounced associations, even after adjusting for age, gender, BMI, and diabetes status (p-Value ≥0.05). The observed correlations of SOST with various clinical parameters suggest its significant role in the diabetic milieu, particularly pronounced in the South Asian population compared to other ethnic groups.

Long-term Mortality and SGLT2 Inhibitors in Type 2 Diabetes with and without renal impairment: An Observational Cohort Study.

AAim: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a vital part of management of type 2 diabetes, as they have been shown to have both cardiovascular and renal benefits along with an improved survival rate in several randomized clinical trials. We designed a retrospective cohort study to investigate the impact of SGLT2 inhibitors on mortality among type 2 diabetes patients. METHODS: Patients with type 2 diabetes who presented to the Dasman Diabetes Institute in Kuwait were followed from January 1st, 2015, until January 20th, 2023. To control for non-random allocation of SGLT2 inhibitors and measured confounders, we performed one-to-one propensity score matching and evaluated outcomes in the matched cohorts using a Cox proportional hazards model. The primary treatment variable was SGLT2 inhibitor use; time to mortality from any cause was used as the outcome of interest. RESULTS: 1551 patients were taking SGLT2 inhibitors, and 1687 patients were not. After propensity score matching, 845 patients were on SGLT2 inhibitors, and 845 patients were not. In post-matching analysis, all-cause mortality was higher among patients who did not take SGLT2 inhibitors compared to patients taking SGLT2 inhibitors (5.2% vs. 2.1%, p=0.0012). The hazard ratio of all-cause mortality in patients taking SGLT2 inhibitors was 0.42 (95% confidence interval [95% CI], 0.24-0.72). Additional adjustment of matching factors did not change the results. CONCLUSION: This observational study demonstrated substantial long-term reduction in mortality risk among patients with type 2 diabetes treated with SGLT2 inhibitors. This is irrespective of the stage of their renal diseases or GLP1 agonist.

Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease progressing to end-stage renal disease. There is a pressing need for the identification of early ADPKD biomarkers to enable timely intervention and the development of effective therapeutic approaches. Here, we profiled human urinary extracellular vesicles small RNAs by small RNA sequencing in patients with ADPKD and compared their differential expression considering healthy control individuals to identify dysregulated small RNAs and analyze downstream interaction to gain insight about molecular pathophysiology. METHODS: This is a cross-sectional study where urine samples were collected from a total of 23 PKD1-ADPKD patients and 28 healthy individuals. Urinary extracellular vesicles were purified, and small RNA was isolated and sequenced. Differentially expressed Small RNA were identified and functional enrichment analysis of the critical miRNAs was performed to identify driver genes and affected pathways. RESULTS: miR-320b, miR-320c, miR-146a-5p, miR-199b-3p, miR-671-5p, miR-1246, miR-8485, miR-3656, has_piR_020497, has_piR_020496 and has_piR_016271 were significantly upregulated in ADPKD patient urine extracellular vesicles and miRNA-29c was significantly downregulated. Five 'driver' target genes (FBRS, EDC3, FMNL3, CTNNBIP1 and KMT2A) were identified. CONCLUSIONS: The findings of the present study make significant contributions to the understanding of ADPKD pathogenesis and to the identification of novel biomarkers and potential drug targets aimed at slowing disease progression in ADPKD.

PKD1 Truncating Mutations Accelerate eGFR Decline in Autosomal Dominant Polycystic Kidney Disease Patients.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disease characterized by the accumulation of fluid-filled cysts in the kidneys, leading to renal volume enlargement and progressive kidney function impairment. Disease severity, though, may vary due to allelic and genetic heterogeneity. This study aimed to determine genotype-phenotype correlations between PKD1 truncating and non-truncating mutations and kidney function decline in ADPKD patients. METHODS: We established a single-center retrospective cohort study in Kuwait where we followed every patient with a confirmed PKD1-ADPKD diagnosis clinically and genetically. Renal function tests were performed annually. We fitted generalized additive mixed effects models with random intercepts for each individual to analyze repeated measures of kidney function across mutation type. We then calculated survival time to kidney failure in a cox proportional hazards model. Models were adjusted for sex, age at visit, and birth year. RESULTS: The study included 22 truncating and 20 non-truncating (42 total) patients followed for an average of 6.6 years (range: 1-12 years). Those with PKD1 truncating mutations had a more rapid rate of eGFR decline (-4.7 mL/min/1.73 m2 per year; 95% CI: -5.0, -4.4) compared to patients with PKD1 non-truncating mutations (-3.5 mL/min/1.73 m2 per year; 95% CI: -4.0, -3.1) (p for interaction <0.001). Kaplan-Meier survival analysis of time to kidney failure showed that patients with PKD1 truncating mutations had a shorter renal survival time (median 51 years) compared to those with non-truncating mutations (median 56 years) (P for log-rank = 0.008). CONCLUSION: In longitudinal and survival analyses, patients with PKD1 truncating mutations showed a faster decline in kidney function compared to patients PKD1 non-truncating mutations. Early identification of patients with PKD1 truncating mutations can, at best, inform early clinical interventions or, at least, help suggest aggressive monitoring.

Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a complicated condition related to type 2 diabetes mellitus (T2D). ANGPTL8 is a hepatic protein highlighted as a risk factor for DN in patients with T2D; additionally, recent evidence from DN studies supports the involvement of growth hormone/IGF/IGF-binding protein axis constituents. The potential link between ANGPTL8 and IGFBPs in DN has not been explored before. Here, we assessed changes in the circulating ANGPTL8 levels in patients with DN and its association with IGFBP-1, -3, and -4. Our data revealed a significant rise in circulating ANGPTL8 in people with DN, 4443.35 ± 396 ng/mL compared to 2059.73 ± 216 ng/mL in people with T2D (p < 0.001). Similarly, levels of IGFBP-3 and -4 were significantly higher in people with DN compared to the T2D group. Interestingly, the rise in ANGPTL8 levels correlated positively with IGFBP-4 levels in T2DM patients with DN (p < 0.001) and this significant correlation disappeared in T2DM patients without DN. It also correlated positively with serum creatinine and negatively with the estimated glomerular filtration rate (eGFR, All < 0.05). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and IGFBP4 was 0.76 (0.69-0.84), p < 0.001, and the specificity was 85.9%. In conclusion, our results showed a significant increase in ANGPTL8 in patients with DN that correlated exclusively with IGFBP-4, implicating a potential role of both proteins in the pathophysiology of DN. Our findings highlight the significance of these biomarkers, suggesting them as promising diagnostic molecules for the detection of diabetic nephropathy.

Increased Glucagon Immunoreactivity in a Rat Model of Diet-induced Obesity following Sleeve Gastrectomy.

OBJECTIVE: Bariatric surgery is currently the most effective treatment for obesity, and procedures such as Roux-en Y gastric bypass and sleeve gastrectomy (SG) also result in rapid improvements in insulin sensitivity and glucose tolerance. In addition, these procedures cause changes in the secretion of various gut-derived hormones. The role these hormones play in the mechanism of the beneficial effects of bariatric surgery is still debated, but nonetheless, their importance provides inspiration for novel obesity-targeted pharmacotherapies. METHODS: Male Sprague Dawley rats were fed either regular chow or a cafeteria diet to induce obesity. A sub-group of the obese animals then underwent either sham surgery or SG. RESULTS: Following a 4-week recovery period, SG rats weighed significantly less than obese or sham-operated rats. Improvements in glucose tolerance and insulin sensitivity also occurred in the SG group, but these were not always statistically significant. We measured the intracellular lipid content of liver samples and found that obese rats showed signs of non-alcoholic fatty liver disease, which were significantly ameliorated by SG. There were significantly higher glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses to a standard mixed meal in the SG group, as well as paradoxically higher glucagon secretion. CONCLUSION: These data highlight the need for more specific anti-glucagon antibodies to characterize the changes in proglucagon-derived peptide concentrations that occur following SG. Further studies are required to determine whether these peptides contribute to the therapeutic effects of SG.

Experience of the Sudanese doctors in surgery of conjoined twins.

Surgical separation of conjoined twins remains one of the most unique and rewarding experiences in the field of pediatric surgery, bearing in mind that this decision is their best chance of survival. These are the first reported cases of successfully separating omphalopagus conjoined twins by the liver in Sudan. After an emergency cesarean section, 62-day-old term-conjoined twins were referred to our pediatric surgery center. Examination revealed well-appearing twins fused from the xiphoid to the umbilicus; imaging confirmed a fused liver with a separate portal and caval structures, necessitating surgical separation and closure, which was done successfully on subsequent hours with well tolerance and recovery discharged on day 21. The second case involved 21-day-old term-conjoined female twins who were fused from the xiphoid to the umbilicus and shared the same cord, as well as complete fusion of the liver with separate other vital organs. They were successfully separated and recovered well.

Data from the batch adsorption of ciprofloxacin and lamivudine from synthetic solution using jamun seed (Syzygium cumini) biochar: Response surface methodology (RSM) optimization.

This dataset expresses the experimental data on the batch adsorption of ciprofloxacin and lamivudine from synthetic solution using jamun seed (JS) (Syzygium cumini) biochar. Independent variables including concentration of pollutants (10-500 ppm), contact time (30-300 min), adsorbent dosage (1-1000 mg), pH (1-14) and adsorbent calcination temperature (250,300, 600 and 750 °C) were studied and optimized using Response Surface Methodology (RSM). Empirical models were developed to predict the maximum removal efficiency of ciprofloxacin and lamivudine, and the results were compared with the experimental data. The removal of polutants was more influenced by concentration, followed by adsorbent dosagage, pH, and contact time and the maximum removal reached 90%.

The genetic landscape of autosomal dominant polycystic kidney disease in Kuwait.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal monogenic disease, characterized by bilateral accumulation of renal fluid-filled cysts leading to progressive renal volume enlargement and gradual impairment of kidney function, often resulting in end-stage renal disease. Kuwait could provide valuable genetic insights about ADPKD, including intrafamilial phenotypic variation, given its large household size. This study aims to provide a comprehensive description of the pathogenic variants linked to ADPKD in the Kuwaiti population using multiple genetic analysis modalities and to describe and analyse the ADPKD phenotypic spectrum in terms of kidney function, kidney volume and renal survival. Methods: A total of 126 ADPKD patients from 11 multiplex families and 25 singletons were recruited into the study. A combination of targeted next-generation sequencing (tNGS), long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification were utilized for genetic diagnosis. Clinical evaluation was conducted through renal function testing and ultrasonographic kidney volume analysis. Results: We identified 29 ADPKD pathogenic mutations from 36 families achieving an overall molecular genetic diagnostic rate of 112/126 (88.9%), including 29/36 (80.6%) in families. A total of 28/36 (77.8%) families had pathogenic mutations in PKD1, of which 17/28 (60.7%) were truncating, and 1/36 (2.8%) had a pathogenic variant in the IFT140 gene. A total of 20/29 (69%) of the identified ADPKD mutations were novel and described for the first time, including a TSC2-PKD1 contiguous syndrome. Clinical analysis indicated that genetically unresolved ADPKD cases had no apparent association between kidney volume and age. Conclusion: We describe for the first time the genetic landscape of ADPKD in Kuwait. The observed genetic heterogeneity underlining ADPKD along with the wide phenotypic spectrum reveal the level of complexity in disease pathophysiology. ADPKD genetic testing could improve the care of patients through improved disease prognostication, guided treatment and genetic counselling. However, to fulfil the potential of genetic testing, it is important to overcome the hurdle of genetically unresolved ADPKD cases.

Safety of Intravenous Iron in CKD Stage 3-5 Patients Not on Dialysis: A Retrospective Cohort Study.

Background: Iron deficiency is common in chronic kidney disease (CKD) patients not on dialysis (ND). Restoring depleted iron stores through intravenous (IV) route is faster and associated with less side effects. There is conflicting data regarding intravenous iron use and its impact on clinical outcomes in this population. Objective: This study aims at evaluating any negative clinical impact associated with IV iron use in CKD patients at stages (3-5) before dialysis. Design: Retrospective chart review. Setting and Population: Chart analysis of ND CKD 3-5 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) patients who received IV iron between January 2013 and January 2018 in 3 major hospitals in Kuwait. Methods: Outcomes analyzed were rates of all-cause hospitalizations, infection-related hospitalizations, mortality rates, and eGFR decline over 12 months after IV iron infusion in this population divided into 3 groups according to CKD stage. Results: A total of 738 patients were included in our analysis. Mean initial hemoglobin concentration was 111.5 ± 15.0 g/L in group 1 (CKD 3: eGFR 30-59 mL/min/1.73 m2), 103.6 ± 17.7 g/L in group 2 (CKD 4: eGFR 15-29 mL/min/1.73 m2), and 99.4 ± 14.5 g/L in group 3 (CKD 5: eGFR < 15 mL/min/1.73 m2 but not on dialysis). All-cause hospitalization and infection-related hospitalization were more common among group 3 subjects (adjusted odds ratio =2.12 [95% confidence interval, CI: 1.32-3.41] and 2.02 [95% CI: 1.15-3.55]), respectively. No deaths occurred during 12 months of follow-up. Limitations: Lack of control group, retrospective study. Conclusion: Intravenous iron use in CKD 3-5 ND is generally safe. Higher hospitalization rates in patients with eGFR <30 mL/min are possibly associated with lower baseline hemoglobin, lower baseline eGFR, and higher comorbidity burden, and not related to iron infusion.

Contexte: La carence en fer est fréquente chez les patients atteints d'insuffisance rénale chronique (IRC) qui ne sont pas sous dialyse (ND). Le rétablissement des réserves de fer par voie intraveineuse (IV) est plus rapide et associé à moins d'effets secondaires. Les données sur l'administration du fer par intraveineuse et son incidence sur les résultats cliniques dans cette population demeurent toutefois contradictoires. Objectif: Cette étude vise à évaluer tout effet clinique négatif associé à l'administration de fer IV chez les patients atteints d'IRC de stade 3 à 5 avant la dialyse. Type d'étude: Examen rétrospectif des dossiers médicaux. Cadre et population: Analyse des dossiers médicaux de patients atteints d'IRC de stade 3 à 5 (DFGe < 60 ml/min/1,73 m2) ND ayant reçu du fer IV entre janvier 2013 et janvier 2018 dans trois grands hôpitaux du Koweït. Méthodologie: Les taux d'hospitalisations toutes causes confondues et d'hospitalisations liées à une infection, le taux de mortalité et le déclin du DFGe ont été mesurés sur une période de 12 mois après la perfusion de fer. La population était divisée en trois groupes selon le stade de l'IRC. Résultats: L'analyse porte sur un total de 738 patients. La concentration initiale moyenne d'hémoglobine était de 111,5 ± 15,0 g/L dans le groupe IRC 3 (DFGe: 30-59 ml/min/1,73 m2), de 103,6 ± 17,7 g/L dans le groupe IRC 4 (DFGe: 15-29 ml/min/1,73 m2) et de 99,4 ± 14,5 g/L dans le groupe IRC 5 (DFGe < 15 ml/min/1,73 m2 sans dialyse). Les hospitalisations toutes causes confondues et les hospitalisations liées à une infection étaient plus fréquentes chez les sujets du groupe IRC 3 (rapport de cotes ajusté = 2,12 [IC à 95 %: 1,32-3,41] et 2,02 [IC 95 %: 1,15-3,55] respectivement). Aucun décès n'est survenu pendant les 12 mois de suivi. Limites: Absence de groupe témoin, étude rétrospective. Conclusion: L'administration de fer IV chez les patients atteints d'IRC de stade 3 à 5 ND est généralement sûre. Le taux d'hospitalisation plus élevé observé chez les patients présentant un DFGe < 30 ml/min est probablement attribuable à des mesures initiales plus faibles pour l'hémoglobine et le DFGe, de même qu'à une charge de comorbidité plus élevée, plutôt qu'à la perfusion de fer.

Geochemical, Mineralogical, and Geomorphological Characterization of Ash Materials as a Tracer for the Origin of Shifting Sands near Oldupai Gorge, Ngorongoro, Tanzania.

Shifting sand (SS) is a single dune-shaped mass of black ash material moving across western Ngorongoro in northern Tanzania. The moving sand has become an important tourist destination for several decades. Despite being part of the important geosites at the Ngorongoro Conservation Area, the nature, origin, and behaviors demonstrated by SS remain poorly understood. This work contributes toward understanding the nature and identification of the possible origin of the SS through the correlation of geochemical, mineralogical, and geomorphological data of ash material from four selected locations in the study area. To achieve this goal, elemental, mineralogical, and morphological characterization of ash samples was performed by energy-dispersive X-ray fluorescence, polarized petrographic microscopy, automated sieve shaker, and binocular microscopy techniques, respectively. Correlation studies were based on magnesian-ferriferous associations, similarities in mineralogy, particle size, shape, and distribution patterns of ash materials, and weather data. There are close similarities in the chemical compositions among ash samples of SS, Ootun area, and Oldoinyo Lengai. Augite and magnetite minerals appear only in samples of SS, Ootun area, and Oldoinyo Lengai, while hornblende appears only in the samples from the Ngorongoro crater. Oldoinyo Lengai rock petrography revealed significant amounts of augite minerals. Blocky and elongated-shaped ash particles dominate the samples from SS, Ootun area, and Oldoinyo Lengai. The particle size of ash materials decreases westwards across the study site. The distribution patterns of ash material align with the west-south-west wind direction. Based on these findings, the study concludes that SS and Ootun ash could be tephra depositions resulting from past volcanic eruptions of Oldoinyo Lengai.

Continued disruptions in health care services and mental health among health care providers during the COVID-19 pandemic in five sub-Saharan African countries.

Background: Continuous monitoring of the pandemic's impact on health service provision and mental health, COVID-19 perceptions, and compliance with prevention measures among health care providers (HCPs) can help with mitigating the pandemic's negative effects. Methods: A computer-assisted telephone interviewing (CATI) survey was conducted among 1499 HCPs in Burkina Faso (Ouagadougou), Ethiopia (Addis Ababa), Nigeria (Lagos and Ibadan), Tanzania (Dar es Salaam), and Ghana (Kintampo). Self-reported mental health, perceptions of the COVID-19 pandemic, and prevention measures available in the workplace were assessed. HCPs' responses to questions regarding the impact of COVID-19 on nine essential health services were summed into a score; high service disruption was defined as a score higher than the total average score across all sites. Modified Poisson regression was used to identify potential factors related to high service disruption. Results: Overall, 26.9% of HCPs reported high service disruption, with considerable differences across sites (from 1.6% in Dar es Salaam to 45.0% in Addis Ababa). A considerable proportion of HCPs reported experiencing mild psychological distress (9.4%), anxiety (8.0%), and social avoidance or rejection (13.9%) due to their profession. Participants in Addis Ababa (absolute risk ratio (ARR) = 2.10; 95% confidence interval (CI) = 1.59-2.74), Lagos (ARR = 1.65; 95% CI = 1.24-2.17), and Kintampo (ARR = 2.61; 95% CI = 1.94-3.52) had a higher likelihood of reporting high service disruption compared to those in Ouagadougou. Reporting ever-testing for COVID-19 (ARR = 0.82; 95% CI = 0.69-0.97) and the presence of COVID-19 guidelines in the workplace (ARR = 0.63; 95% CI = 0.53-0.77) were both associated with lower reported health service disruption among HCPs. Conclusion: The COVID-19 pandemic continues to disrupt essential health services and present a challenge to HCPs' mental health, with important differences across countries and settings; interventions are needed to mitigate these negative effects of the pandemic.

Attenuation of nitrate from aqueous solution using raw and surface modified biosorbents from Adansonia digitata fruit pericarp.

The prevalence of nitrate in potable water is a serious environmental concern. Several methods for eliminating nitrate from water have been made and implemented. During the course of this research, raw (RADFP) and surface-modified fruit pericarp (SMADFP) biosorbents derived from the Adansonia digitata plant were applied in order to remove nitrate from an aqueous solution. The external features of the biosorbents were studied with the aids of SEM and BET. The FT-IR spectrometer was utilized for identification of the functional groups of the adsorbents. A UV-Vis device was used to quantify the nitrate concentration. The adsorbents under investigation exhibit a heterogeneous pore structure with a considerable number of mesopores, with surface areas of 361.527 and 379.877 m2 per gram for RADFP and SMADFP, respectively. FT-IR spectra revealed the presence of carboxyl, hydroxyl, carbonyl, and halogen groups on the adsorbent. The maximum nitrate removal efficiencies of RADFP and SMADFP were 64.55 and 88.95%, respectively. The maximum adsorption efficiencies are achieved when the pH is 2, the starting concentration is 27.50 mg/L, the contact period is 75.00 min, and the amount of biosorbent is 5.50 g. RADFP and SMADFP have a removal capacity of 12.45 as well as 25.18 mg per gram and adsorption intensity of 3.2300 and 5.4500, respectively. The investigational values for the elimination of nitrate ions concurred well to both Freundlich and Langmuir models with R2 values of 0.99917 and 0.99763 for RADFP and SMADFP, respectively, and pseudo-second-order kinetic model with R2 values of 0.99817 and 0.99947, respectively for RADFP and SMADFP. It can be concluded that SMADFP is a relatively better biosorbent than RADFP, which will be utilizable for the remediation of nitrate from an aqueous solution.

Discovery of natural products to block SARS-CoV-2 S-protein interaction with Neuropilin-1 receptor: A molecular dynamics simulation approach.

Neuropilin-1 (NRP1) is a widely expressed cell surface receptor protein characterized by its pleiotropic function. Recent reports highlighted NRP1 as an additional entry point of the SARS-CoV-2 virus, enhancing viral infectivity by interacting with the S-protein of SARS-CoV-2. The ubiquitous distribution and mechanism of action of NRP1 enable the SARS-CoV-2 virus to attack multiple organs in the body simultaneously. Therefore, blocking NRP1 is a potential therapeutic approach against SARS-CoV-2 infection. The current study screened the South African natural compounds database (SANCDB) for molecules that can disrupt the SARS-CoV-2 S protein-NRP1 interaction as a potential antiviral target for SARS-CoV-2 cellular entry. Following excessive screening and validation analysis 3-O-Methylquercetin and Esculetin were identified as potential compounds to disrupt the S-protein-NRP1 interaction. Furthermore, to understand the conformational stability and dynamic features between NRP1 interaction with the selected natural products, we performed 200 ns molecular dynamics (MD) simulations. In addition, molecular mechanics-generalized Born surface area (MM/GBSA) was utilized to calculate the free binding energies of the natural products interacting with NRP1. 3-O-methylquercetin showed an inhibitory effect with binding energies ΔG of -25.52 ±â€¯0.04 kcal/mol to NRP1, indicating the possible disruption of the NRP1-S-protein interaction. Our analysis demonstrated that 3-O-methylquercetin presents a potential antiviral compound against SARS-CoV-2 infectivity. These results set the path for future functional in-vitro and in-vivo studies in SARS-CoV-2 research.

Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients With Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study.

Introduction: Few data exist regarding the immunogenicity of the third dose of BNT162b2 relative to the second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy. Method: This is a prospective single-center observational study conducted from January 1, 2022 to February 28, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with a confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine. Patients who received two doses of BNT162b2 vaccine (second dose group) were compared to patients who had received three doses of BNT162b2 vaccine [third dose (booster) group]. Patients were excluded if they were infected or had symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40-45 weeks from the first dose of BNT162b2 vaccine in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated. Results: In total, 162 patients with IBD and receiving infliximab combination therapy were recruited, and the number of patients in both the second dose group and third dose (booster) group was 81. Mean age was 35 years old in both groups. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/ml (43, 192)] compared to patients who received the third booster dose [207 BAU/ml (181, 234)] (P = 0.003). Neutralizing antibody levels were also lower after the second dose [80% (21, 95)] compared to patients who received the third booster dose [96% (93, 99)] (P ≤ 0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was 96.3%, whereas it was 86.4% in the second dose group. The percentage of participants who received the third (booster) dose and achieved a positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was 88.9% in the participants who received the second dose only. Conclusion: Most patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40-45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received two doses only compared to patients who received a third dose. A longer follow-up study is needed to evaluate decay in antibodies over time.

Changes in the expression of meteorin-like (METRNL), irisin (FNDC5), and uncoupling proteins (UCPs) after bariatric surgery.

OBJECTIVE: Bariatric surgery is currently the most effective treatment for severe obesity. This study aims to investigate the changes in expression levels of meteorin-like protein (METRNL), irisin (FNDC5), and uncoupling proteins (UCP) 1/2/3 following bariatric surgery to understand their involvement in enhancing metabolism after surgery. METHOD: A total of 40 participants were enrolled in this interventional study, 20 with obesity BMI ≥ 35 kg/m2 and 20 with BMI ≤ 25 kg/m2 . Bariatric surgery (laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) was performed. The levels of various molecules of interest were analyzed before and after surgery. RESULTS: Gene expression analysis revealed significantly higher levels of METRNL, UCP1, and UCP3 in individuals with obesity when compared with healthy individuals before surgery (p < 0.05). Gene expression levels of METRNL and UCP2 showed a significant increase after bariatric surgery (p < 0.05). METRNL plasma level was significantly higher in individuals with obesity before surgery (mean [SEM], 55,222.6 [1,421.1] pg/mL, p = 0.0319), as well as at 6 and 12 months (57,537.3 [1,303.9] pg/mL, p = 0.0005; 59,334.9 [1,214.3] pg/mL, p < 0.0001) after surgery. CONCLUSION: The changes in the levels of various molecules of interest support their possible involvement in the inflammatory and thermogenic responses following bariatric surgery.