Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study.

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of metabolic disorders. However, there is limited knowledge regarding FABP4 expression in diabetes and obesity, especially about different age groups, genders, and ethnicities. This study aims to investigate the association between FABP4 levels, diabetes mellitus, and obesity within various ethnic groups. We measured plasma FABP4 concentrations in a cohort of 2083 patients from the KDEP study and gathered anthropometric data. Additionally, we collected and analyzed clinical, biochemical, and glycemic markers using multivariate regression analysis. The average FABP4 concentration was significantly higher in female participants than in males (18.8 ng/mL vs. 14.4 ng/mL, p < 0.001, respectively), and in those over 50 years old compared to those under 50 years of age (19.3 ng/mL vs. 16.2 ng/mL, p < 0.001, respectively). In this study, significant positive associations were found between the plasma level of FABP4 and obesity markers: BMI (r = 0.496, p < 0.001), hip circumference (r = 0.463, p < 0.001), and waist circumference (WC) (r = 0.436, p < 0.001). Similar observations were also seen with glycemic markers, which included HbA1c (r = 0.126, p < 0.001), fasting blood glucose (FBG) (r = 0.184, p < 0.001), fasting insulin (r = 0.326, p < 0.001), and HOMA-IR (r = 0.333, p < 0.001). Importantly, these associations remained significant even after adjusting for age, gender, and ethnicity. Furthermore, FABP4 levels were negatively associated with male gender (ß: -3.85, 95% CI: -4.92, -2.77, p < 0.001), and positively associated with age (ß: 0.14, 95% CI: 0.096, 0.183, p < 0.001), BMI (ß: 0.74, 95% CI: 0.644, 0.836, p < 0.001), and fasting insulin (ß: 0.115, 95% CI: 0.091, 0.138, p < 0.001). In this study, plasma FABP4 levels were significantly higher in diabetic and obese participants, and they were strongly influenced by age, gender, and ethnicity. These findings suggest that FABP4 may serve as a valuable prognostic and diagnostic marker for obesity and diabetes, particularly among female patients, individuals over 50 years old, and specific ethnic groups.

Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. AIM: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. DATA SOURCE: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. DATA SYNTHESIS: Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI  - 0.49 to  - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI  - 1.34 to  - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD:  - 0.47; 95% CI  - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD:  - 0.37 µg/dL; 95% CI  - 0.05 to  - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD:  - 1.67; 95% CI  - 2.27 to  - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. CONCLUSION: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. PROSPERO REGISTRATION NO: CRD42020178783.

Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. DESIGN: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I² = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I² = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I² = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I² = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. CONCLUSIONS: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

Effect of pharmacological interventions on lipid profiles and C-reactive protein in polycystic ovary syndrome: A systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.

Impact of pharmacological interventions on anthropometric indices in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight. OBJECTIVE: To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021. STUDY SELECTION: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020. DATA EXTRACTION: Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: 80 RCTs were included in the meta-analysis. Metformin vs placebo showed significant reduction in the mean body weight (MD: -3.13 kg; 95% confidence interval [CI]: -5.33 to -0.93, I² = 5%) and the mean body mass index (BMI) (MD: -0.75 kg/m2 ; 95% CI: -1.15 to -0.36, I² = 0%). There was a significant reduction in the mean BMI with orlistat versus placebo (MD: -1.33 kg/m²; 95% CI: -2.16 to -0.66, I² = 0.0%), acarbose versus metformin (MD: -1.26 kg/m²; 95% CI: -2.13 to -0.38, I² = 0%), and metformin versus pioglitazone (MD: -0.91 kg/m²; 95% CI: -1.62 to -0.19, I² = 0%). A significant increase in the mean BMI was also observed in pioglitazone versus placebo (MD: + 2.59 kg/m²; 95% CI: 1.78-3.38, I² = 0%) and in rosiglitazone versus metformin (MD: + 0.80 kg/m²; 95% CI: 0.32-1.27, I² = 3%). There was a significant reduction in the mean waist circumference (WC) with metformin versus placebo (MD: -1.21 cm; 95% CI: -3.71 to 1.29, I² = 0%) while a significant increase in the mean WC with pioglitazone versus placebo (MD: + 5.45 cm; 95% CI: 2.18-8.71, I² = 0%). CONCLUSION: Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.

Structure, functions, performance and gaps of event-based surveillance (EBS) in Sudan, 2021: a cross-sectional review.

BACKGROUND: Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward.  METHODS: The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate. RESULTS: Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors. CONCLUSION: The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.

The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. PURPOSE: The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. METHODS: Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). RESULTS: The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). CONCLUSION: High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

Hyperthyroidism and bone mineral density: Dissecting the causal association with Mendelian randomization analysis.

INTRODUCTION: Untreated hyperthyroidism is associated with accelerated bone turnover, low bone mineral density (BMD) and increased susceptibility to fragility fractures. Although treatment appears to improve or even reverse some of these adverse skeletal effects, there is limited guidance on routine BMD assessment in hyperthyroid patients following treatment. By using Mendelian randomization (MR) analysis, we aimed to assess the causal association of hyperthyroid thyroid states with BMD and fractures using the UK Biobank. METHODS: This MR analysis included data from 473 818 participants (women: 54% of the total sample, the median age of 58.0 years (IQR = 50-63 years), median body mass index (BMI) of 26.70 (IQR + 24.11-29.82 kg/m2 ) as part of the UK Biobank study. The study outcomes were heel BMD assessed by quantitative ultrasound of the heel and self-reported fractures. Beta-weighted genetic risk score analysis was performed using 19 single nucleotide polymorphisms (SNPs) for Graves' disease, 9 SNPs for hyperthyroidism and 11 SNPs for autoimmune thyroiditis. Since the unadjusted risk score MR is equivalent to the inverse-variance weighted method, the genetic risk score analysis was adjusted for age, gender and BMI. Sensitivity analyses were conducted using the Mendelian randomization-Egger (MR-Egger) and the inverse-variance weighted estimate methods. Replication analysis was performed using the GEnetic Factors for Osteoporosis (GEFOS) consortium data. RESULTS: MR analysis using beta-weighted genetic risk score showed no association of genetic risk for Graves' disease (Beta = -0.01, P-value = .10), autoimmune thyroiditis (Beta = -0.006 P-value = .25) and hyperthyroidism (Beta = -0.009, P-value = .18) with heel ultrasound BMD. MR-Egger and inverse-variance MR methods in UK Biobank and GEFOS consortium confirmed these findings. The genetic risk for these hyperthyroid conditions was not associated with an increased risk of fractures. CONCLUSION: Our study shows that excess genetic risk for Graves' autoimmune thyroiditis and hyperthyroidism does not increase the risk for low BMD and is not associated fractures in the Caucasian population. Our findings do not support routine screening for osteoporosis following definitive treatment of hyperthyroid states.

The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem with increasing prevalence among overweight and obese patients. It is strongly associated with conditions of insulin resistance including type 2 diabetes mellitus (T2DM) and obesity. It has detrimental consequences ranged from simple steatosis to irreversible hepatic fibrosis and cirrhosis. Curcumin is a dietary polyphenol with potential effect in improving NAFLD. Therefore, the aim of this trial was to examine the effect of curcumin supplementation on various aspects of NAFLD. In this trial, a total number of 80 patients were randomised to receive either curcumin at 250 mg daily or placebo for 2 months. Lipid profiles, hepatic enzymes, anthropometric indices and hepatic fat mass were assessed at the baseline and the end of the trial, and compared within the groups. The grade of hepatic steatosis, and serum aspartate aminotransferase (AST) levels were significantly reduced in the curcumin group (p = 0.015 and p = 0.007, respectively) compared to the placebo. There was also a significant reduction in high density lipoprotein (HDL) levels and anthropometric indices in both groups with no significant differences between the two groups. Low dose phospholipid curcumin supplementation each day for 2 months showed significant reduction in hepatic steatosis and enzymes in patients with NAFLD compared to placebo. Further studies of longer duration and higher dosages are needed to assess its effect on other parameters of NAFLD including cardiovascular risk.

Genetic and biochemical characterization of thermophilic ß-cyclodextrin glucanotransferase from Gracilibacillus alcaliphilus SK51.001.

BACKGROUND: Gracilibacillus alcaliphilus SK51.001, a strain that produces ß-CGTase (ß-cyclodextrin glucanotransferase) (EC 2.4.1.19), was screened and isolated from Sudanese soil. The objective of this study was to sequence and characterize the ß-CGTase gene from G. alcaliphilus SK51.001. RESULTS: According to 16S rRNA analysis of the strain and its morphological shape, it was identified as G. alcaliphilus. The ß-CGTase gene was successfully cloned, sequenced, and expressed in Escherichia coli BL21. This gene showed 706 amino acid residues including 33 amino acids as a signal peptide. The active site residues of G. alcaliphilus SK51.001CGTase were described using enzyme modeling and docking with the products. The estimated molecular mass of G. alcaliphilus SK51.001CGTase was approximately 74 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the evaluation of the gel filtration showed approximately 85 kDa, which means G. alcaliphilus SK51.001CGTase is a monomer. The optimum temperature and pH of G. alcaliphilus SK51.001CGTase were 60 °C and 7.0 respectively. Gracilibacillus alcaliphilus SK51.001CGTase was comparatively stable at a pH levels between 6.0 and 9.0 and temperatures of 30-50 °C. The activity of G. alcaliphilus SK51.001CGTase was increased by Ni2+ , and Co2+ but inhibited by Al3+ and Fe3+ . The kinetic parameters of Km and Vmax were 2068.52 µg mL-1 and 0.13 µmol mL-1  min-1 , respectively. CONCLUSION: Gracilibacillus alcaliphilus SK51.001CGTase could hydrolyze soluble starch into α-, ß-, and γ-cyclodextrin in a ratio of 2: 83: 15% respectively. This high ratio production of ß-CD could allow the enzyme to be used in ß-CD production. © 2020 Society of Chemical Industry.

Vitamin D deficiency increases risk of nephropathy and cardiovascular diseases in Type 2 diabetes mellitus patients.

BACKGROUND: Vitamin D (VD) deficiency is associated with insulin function and secretion. It is linked with diabetes mellitus (DM) progression, and complications were also recorded. Therefore, the current study aimed to investigate serum VD level in Type 2 DM (T2DM) patients and its association with diabetic nephropathy and cardiovascular diseases (CVD). MATERIALS AND METHODS: In this cross-sectional study, 205 patients with Type 2 diabetes age ranged from 39 to 75 years old were enrolled. Serum VD, high-sensitivity C-reactive protein (hs-CRP), and hemoglobin A1c (HbA1c) were measured. In addition, urinary albumin:creatinine ratio (ACR) was estimated. RESULTS: Patients with Type 2 diabetes had a 78.5% VD level <30 ng/m. ACR and hs-CRP levels were significantly increased in patients with diabetes with VD <30 ng/m (P = 0.011 and P = 0.008, respectively). Female had significantly lower VD level than male P < 0.001. Patients exposed to sunlight had significantly higher VD level and lower hs-CRP levels compared with less-exposed, P value (0.001 and <0.001), respectively. Exercise significantly increased VD and decreased ACR levels in DM patients, P value (0.046 and 0.002), respectively. VD was positively associated with age (r = 0.355 P = 0.040) and negatively correlate with BMI (r = -0.502 P = 0.009), duration of disease (r = -0.498 P = 0.003), ACR (r = -0.384 P = 0.015), and HbA1c (r = -0.327 P = 0.032). CONCLUSION: The evidence from this study suggest that patients with Type 2 diabetes with VD deficiency are at higher risk for developing CVD and nephropathy.

Hepatitis B Virus Seroprevalence Among Children With Cancer in Sudan.

BACKGROUND: The seroprevalence of hepatitis B among children with cancer in Sudan is unknown. The aim of this study was to detect the seroprevalence of hepatitis B virus (HBV) infection in children with malignancy and its correlation with different risk factors. PROCEDURE: This study included 178 children with malignancy presenting to the Radioisotope Center in Khartoum during the period of May-July 2011. Sixty-four healthy children served as controls. Sera from patients and controls were investigated for HBV total anti-core antibody, HBV surface antigen (HBsAg), and HBV e antigen (HBeAg). RESULTS: HBV total anti-core antibody was positive in 71/178 (39.9%), HBsAg was positive in 38 (21.3%), and HBeAg was positive in 19 (10.7%). Blood product transfusion, surgical exposure, chemotherapy, malignancy type, and sex did not affect the seroprevalence of HBV in this study. Vaccinated children had reduced rates of exposure compared to non-vaccinated patients. CONCLUSION: There is a high seroprevalence of HBV in children with malignancies in Sudan. Vaccination appears to play a major protective role.

Profound metabolic acidosis in association with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy: a case report and literature review.

Calciphylaxis, also known as Calcific uremic arteriolopathy (CUA), is a serious disorder that presents with skin necrosis due to calcification of dermal and subcutaneous adipose tissue capillaries and arterioles. The condition occurs primarily in patients with end-stage renal disease (ESRD) on dialysis, and it carries high morbidity and mortality, primarily due to sepsis, with an estimated six-month survival of approximately 50%. Although there are no high-quality studies to guide the optimal treatment approach for patients with calciphylaxis, many retrospective studies and case series support treatment with sodium thiosulfate (STS). Despite the frequent use of STS as an off-label treatment, data regarding its safety and efficacy are limited. STS has generally been considered a safe drug with mild side effects. However, severe metabolic acidosis associated with STS is a rare and life-threatening complication of STS treatment and is often unpredictable. Herein, we report a 64-year-old female with ESRD on peritoneal dialysis (PD) who presented with a profound high anion gap metabolic acidosis and severe hyperkalemia while on STS treatment for CUA. No other etiology for her severe metabolic acidosis other than STS was identified. ESRD patients receiving STS should be monitored closely for this side effect. Dose reduction, increasing the duration of infusion, or even discontinuing STS treatment should be considered if severe metabolic acidosis develops.

The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. METHODS: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20 mmol/L; 95% CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47 mmol/L; 95% CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95% CI - 1.25-0.00, p = 0.05). CONCLUSION: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO REGISTRATION NO: CRD42020178783.

Epidemiological observations and management challenges in extrapedal mycetoma: A three-decade review of 420 cases.

Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep tissues and bone. The disease predominately affects the limbs, and extrapedal mycetoma is rarely reported. The reported extrapedal ones are characterised by high morbidity and mortality. This communication reports on 420 patients with extrapedal mycetoma seen and managed at the Mycetoma Research Centre (MRC), University of Khartoum, between January 1991 and December 2021. In this descriptive, cross-sectional, hospital-based study, the electronic records of all mycetoma-confirmed patients seen during the study period were carefully and meticulously reviewed. The confirmed patients with extrapedal mycetoma were included in this study. The study included 420 patients with extrapedal mycetoma, 298 (70.7%) had eumycetoma, and 122 (29.3%) had actinomycetoma. There were 343 male patients (81.7%) and 77 (18.3%) females, with a male-to-female ratio of 4:1. Their ages ranged between 1.5 and 95 years, with a median of 28 years. Most of the patients were students and farmers. The majority of patients were from El Gezira, North Kordofan, and the White Nile States. Mycetoma was painful in 21%, and a family history of mycetoma was recorded in 11.5% of patients. The buttocks (37.9%) and head and neck (16.9%) were affected most. Less frequently affected sites were the trunk and back (12%) each, abdominal and chest walls (4.5%) each and loin (1%). The prominent clinical presentation findings were multiple sinuses discharging grains (55%), massive swellings (46%), and lymphadenopathy (11.5%). Less commonly observed clinical findings were local hyperhidrosis (5.3%) and dilated tortuous veins close to mycetoma lesions (0.5%). The study showed that 204 patients (48.6%) had clinical improvement in terms of decreased lesion size and healing of sinuses following medical therapy. Sixty-six patients (15.7%) had no noticeable improvement. The lesion continued progressing despite treatment in 44 patients (10.5%). In the study, 118 patients were on regular follow-up, and in this group, a cure was documented in 25 patients (21.1%) with eumycetoma and 23 (19.4%) with actinomycetoma. Post-operative recurrence among eumycetoma patients was 40%, with a 1% mortality rate. The treatment outcome was unsatisfactory, characterised by a low cure rate, high recurrence (40%) and follow-up dropout (57%) rates. This emphasises the importance of early case detection and management, objective health education programmes and thorough patient counselling to urge people to seek treatment early and reduce dropouts.

Therapeutic advances in obesity management: an overview of the therapeutic interventions.

Obesity has become a global epidemic in the modern world, significantly impacting the global healthcare economy. Lifestyle interventions remain the primary approach to managing obesity, with medical therapy considered a secondary option, often used in conjunction with lifestyle modifications. In recent years, there has been a proliferation of newer therapeutic agents, revolutionizing the treatment landscape for obesity. Notably, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, liraglutide, and the recently approved dual GLP-1/GIP RAs agonist tirzepatide, have emerged as effective medications for managing obesity, resulting in significant weight loss. These agents not only promote weight reduction but also improve metabolic parameters, including lipid profiles, glucose levels, and central adiposity. On the other hand, bariatric surgery has demonstrated superior efficacy in achieving weight reduction and addressing overall metabolic imbalances. However, with ongoing technological advancements, there is an ongoing debate regarding whether personalized medicine, targeting specific components, will shape the future of developing novel therapeutic agents for obesity management.

An ingestible self-propelling device for intestinal reanimation.

Postoperative ileus (POI) is the leading cause of prolonged hospital stay after abdominal surgery and is characterized by a functional paralysis of the digestive tract, leading to symptoms such as constipation, vomiting, and functional obstruction. Current treatments are mainly supportive and inefficacious and yield acute side effects. Although electrical stimulation studies have demonstrated encouraging pacing and entraining of the intestinal slow waves, no devices exist today to enable targeted intestinal reanimation. Here, we developed an ingestible self-propelling device for intestinal reanimation (INSPIRE) capable of restoring peristalsis through luminal electrical stimulation. Optimizing mechanical, material, and electrical design parameters, we validated optimal deployment, intestinal electrical luminal contact, self-propelling capability, safety, and degradation of the device in ex vivo and in vivo swine models. We compared the INSPIRE's effect on motility in models of normal and depressed motility and chemically induced ileus. Intestinal contraction improved by 44% in anesthetized animals and up to 140% in chemically induced ileus cases. In addition, passage time decreased from, on average, 8.6 days in controls to 2.5 days with the INSPIRE device, demonstrating significant improvement in motility. Luminal electrical stimulation of the intestine via the INSPIRE efficaciously restored peristaltic activity. This noninvasive option offers a promising solution for the treatment of ileus and other motility disorders.

Perceived Social Stigma of Cutaneous Leishmaniasis in Hubuna, Saudi Arabia.

Background: Cutaneous Leishmaniasis (CL) is a vector-borne skin infection that remains prevalent in regions with poor socioeconomic conditions. Stigmatization occurs when individuals with physical or psychological disorders interact with societal stereotypes. The aim of this study was to explore the perceived social stigma surrounding CL among people residing in Hubuna, Saudi Arabia. Methods: This cross-sectional community-based survey recruited 618 individuals aged 18 years and above using the snowball sampling technique to reach hidden cases within the target population. Data was collected using a self-administered questionnaire and the Explanatory Model Interview Catalogue for Perceived Social Stigma (EMIC-SS-12) was used to assess the level of perceived social stigma. It includes questions on demographic variables, behaviors, and experiences. The analysis was performed using SPSS. Results: The study included 618 participants, the majority of whom were women and girls (54.2%), with a mean age of 28 ± 12.7 years. The median score for perceived social stigma was 26.0. Only 2.1% (n = 13) of participants had the highest EMIC-SS-12 score of 36, while 7.6% (n = 47) scored zero. The mean score for overall perceived social stigma was 1.89 ± 0.91, while the mean score for experienced stigma was 1.99 ± 1.02. Univariate analysis showed that sex, employment, location of lesions, and number of lesions were insignificantly associated with stigmatization (P-value < 0.05), because these associations were uncertain because the CI includes or very close to 1. Conclusion: The study reveals insights into stigmatization associated with CL in the Habuna area of Saudi Arabia. It found that the median of perceived social stigma was 26. Factors such as sex, employment status, and location of the lesion are uncertainly associated with stigma. It is crucial to explore negative behaviors and perceptions and develop suitable health education programs.

Metabolic and Endocrine Complications of Long-COVID-19: A Review.

Over the past two years, the outbreak of coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has centralized the interest of the health care systems and the scientific world. The majority of COVID-19-infected individuals recover fully. However, about 12-50% of patients experience various mid- and long-term effects after recovering from the initial illness. These mid- and long-term effects are collectively known as post-COVID-19 condition or 'long-COVID'. In the coming months, the long-term consequences of COVID-19 on the metabolic and endocrine systems may expect to rise and pose a global healthcare challenge. This review article discusses the possible metabolic and endocrine complications of long-COVID and the relevant research findings.