Zinc oxide nanoparticles-doped curcumin-assisted recovery of rheumatoid arthritis and antioxidant status in experimental rabbits.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and synovial joint destruction. Aims: The current study investigated the possible beneficial effect of zinc oxide nanoparticles doped curcumin (ZnONPs-DC) on the recovery of RA and antioxidant status of experimental rabbits. Methods: RA was induced in experimental rabbits by injecting complete Freund's adjuvant and collagen type-II emulsion (100 µL/kg body weight) in the base of their tail. Arthritic rabbits were orally treated with ZnONPs, curcumin, and ZnONPs-DC(250 µL/kg bodyweight). Serumsamples fromthe control and study groupswere collected before and afterRAinduction and after treatment. The sera were subjected to analysis of biological markers of RA and antioxidant status. Results: The complete Freund's adjuvant and collagen type II treatment resulted in positive rheumatoid factor and C-reactive protein elevated oxidative stress and decreased antioxidant potential. Each treatment showed the absence of rheumatoid factor and C-reactive protein decreased oxidative stress and improved antioxidant potential compared to the control. However, ZnONPs-DC treatment showed a comparatively higher decline in serum malondialdehyde MDA content and an elevation in the antioxidant activity of RA animals. Conclusions: In conclusion, using zinc oxide nanoparticles-doped curcumin may be an effective anti-arthritic and anti-inflammatory drug in controlling RA.

Epigenetically dysregulated NOTCH-Delta-HES signaling cascade can serve as a subtype classifier for acute lymphoblastic leukemia.

The NOTCH-Delta-HES signaling cascade is regarded as a double-edged sword owing to its dual tumor-suppressor and oncogenic roles, in different cellular environments. In the T-cells, it supports leukemogenesis by promoting differentiation while in B-cells, it controls leukemogenesis by inhibiting early differentiation/inducing growth arrest in the lead to apoptosis. The present study was undertaken to assess if this bi-faceted behavior of NOTCH family can be exploited as a diagnostic biomarker or subtype classifier of acute lymphoblastic leukemia (ALL). In this pursuit, expression of seven NOTCH cascade genes was analyzed in bone marrow (BM) biopsy and blood plasma (BP) of pediatric ALL patients using quantitative PCR (qPCR). Further, promoter DNA methylation status of the differentially expressed genes (DEGs) was assessed by methylation-specific qMSP and validated through bisulphite amplicon sequencing. Whereas hypermethylation of JAG1, DLL1, and HES-2, HES-4, and HES-5 was observed in all patients, NOTCH3 was found hypermethylated specifically in Pre-B ALL cases while DLL4 in Pre-T ALL cases. Aberrant DNA methylation strongly correlated with downregulated gene expression, which restored at complete remission stage as observed in "follow-up/post-treatment" subjects. The subtype-specific ROC curve analysis and Kaplan-Meier survival analysis predicted a clinically applicable diagnostic and prognostic potential of the panel. Moreover, the logistic regression model (Pre-B vs Pre-T ALL) was found to be the best-fitted model (McFadden's R2 = 0.28, F1 measure = 0.99). Whether analyzed in BM-aspirates or blood plasma, the NOTCH epigenetic signatures displayed comparable results (p < 0.001), advocating the potential of NOTCH-Delta-HES cascade, as a subtype classifier, in minimally invasive diagnosis of ALL.

Social isolation during the COVID-19 pandemic is associated with the decline in cognitive functioning in young adults.

Coronaviruses have caused widespread disease and death worldwide, leading to the implementation of lockdown measures and the closure of educational institutions in various countries. This research aims to investigate the impact of social isolation on the cognitive functioning of young students. The study included 84 subjects, with 48 being socially isolated and 36 non-isolated individuals. The participants' mental health was assessed using the Mini-Mental State Examination (MMSE), while cognitive functions were evaluated through attention-switching tasks (AST), pattern recognition memory (PRM), and choice reaction time (CRT) tests utilizing the Cambridge Neuropsychological Automated Battery (CANTAB) software. The socially isolated group had an average age of 21.3 ± 1.1 years, whereas the non-isolated group had an average age of 22.8 ± 2.0 years. The MMSE scores were 25.8 ± 1.6 for the socially isolated group and 28.6 ± 1.3 for the non-isolated group. In terms of cognitive functioning, there were significant differences (p = 0.000) observed in the values of AST correct latency for non-switching blocks (blocks 3 and 5) between the socially isolated group (608.1 ± 139.2) and the non-isolated group (499.5 ± 67.8). Similarly, the AST mean correct latency for switching blocks (block 7) was significantly different (p = 0.012) between the socially isolated group (784.4 ± 212.5) and the non-isolated group (671.8 ± 175.6). The socially isolated group exhibited significantly higher values in AST correct mean latency, AST congruent mean latency, AST incongruent mean latency, and AST percent mean correct trials compared to the non-isolated group. Additionally, the PRM mean percent correct significantly differed (p = 0.000) between the isolated group (81.3 ± 12.0) and the non-isolated group (91.9 ± 9.2). The isolated group also showed a higher CRT correct mean latency (482.4 ± 128.9) than the non-isolated group (451.0 ± 59.0), however the difference was not significant. In conclusion, social isolation during the COVID-19 pandemic has resulted in a decline in the cognitive functioning of young students.

Sofosbuvir and Velpatasvir Regimen Outcome for Chronic Hepatitis C Patients With End-Stage Renal Disease Undergoing Hemodialysis.

Background Patients on hemodialysis (HD) are most likely to contract hepatitis C (HCV) infection, which is associated with significant morbidity and disease progression. Direct-acting antivirals (DAAs) are safe and tolerable in chronic kidney disease (CKD) with a 90-100% cure rate, and limited data exist regarding their efficacy in end-stage renal disease (ESRD), particularly for HD patients in South Asia. The study aimed to assess the outcome of a 12-week sofosbuvir (SOF) and velpatasvir (VEL) treatment regimen on ESRD patients with chronic HCV infection undergoing HD in the Pakistani Asian population. Methodology This prospective cohort study was conducted between January 2022 and January 2023 at the outpatient nephrology and gastroenterology clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan. This study included a total of 220 ESRD patients fulfilling the inclusion criteria, aged 20-55 years, who had been undergoing weekly HD sessions for at least two years, with acquired HCV infection. Data on demographic and clinical characteristics were collected through patient interviews. Laboratory and dialysis profiling was executed to assess ESRD and discover the underlying cause by ultrasound abdomen, blood pressure measurement by sphygmomanometer, random blood sugar for diabetes, and taking note of the duration and frequency of dialysis. HCV RNA PCR was done at selected intervals to evaluate the virological response to treatment. Sustained virological response (SVR), liver cirrhosis status, and number of weekly HD sessions were compared at one year of SOF/VEL regimen. Results The mean age of patients with ESRD was 41.8 with a standard deviation (SD) of 9.3 years, and HCV diagnosis was 1.3 years with SD of 0.4 years; 52.7% (n=116) were males, 47.3% (n=104) were females, 75% (n=165) were urban dwellers, and 93.6% (n=206) were married. CKD that requires dialysis was caused mainly by hypertension (78, 35%), diabetes mellitus type 2 (52, 24%), bilateral small kidney disease (40, 18%), and others (34, 16%). One hundred and six (48.2%) received dialysis thrice weekly, 83 (37.7%) twice, and 31 (14.1%) once weekly. The study monitored the rapid virological response (RVR) at four weeks of SOF/VEL regimen in 89.5% of ESRD patients, observed end-of-treatment response (ETR) at 12 weeks in 93.2%, and noted 91.4% SVR response at one year. Only four (1.8%) relapses were observed in the study, which was statistically insignificant. The status of liver cirrhosis showed a 50% improvement, decreasing from 40% to 20%. The frequency of weekly HD sessions decreased from thrice to twice-thrice a week. Conclusion The prevalence of contracting HCV is high among CKD and dialysis ESRD patients. All-oral DAA therapy has revolutionized HCV treatment with co-morbidities. Renal functions improved after the SOF/VEL regimen for chronic HCV infection in ESRD patients undergoing HD, with the number of weekly dialysis sessions reduced and SVR reaching 91.4%. Thus, a single-tablet, pan-genotypic DAA regimen of SOF/VEL for 12 weeks is safe, effective, and tolerable regardless of the underlying etiology of ESRD, complications of cirrhosis, HCV genotype, or previous treatment exposure. The successful treatment of HCV and achieving SVR lowers the risk of ESRD complications, improves extra-hepatic manifestations, and greatly enhances survival. Further studies are warranted after the availability of other DAAs to confirm findings with no limitations.

Metabolic Syndrome in Type 2 Diabetes Mellitus Patients: Prevalence, Risk Factors, and Associated Microvascular Complications.

Background The chronic macro and microvascular complications of diabetes mellitus pose serious health challenges. Metabolic syndrome (MetSy) is characterized by central obesity, glucose intolerance, hyperinsulinemia, low high-density lipoproteins (HDLs), high triglycerides (TGs), and hypertension. MetSy precedes or accompanies diabetes, and it has been linked to an increased risk of cardiovascular disease and premature death. This study aimed to estimate prevalence, identify risk factors, and evaluate associated microvascular complications among MetSy patients with type 2 diabetes mellitus (T2DM). Methodology Over the period of March 20, 2022, to March 31, 2023, a prospective cohort study was conducted at the Outdoor Clinic and Medicine Department of Sheikh Zayed Hospital, Rahim Yar Khan. Based on the International Diabetes Federation MetSy criteria, a total of 160 patients fulfilling the inclusion criteria were selected. A special proforma was used to obtain sociodemographic, clinical, and laboratory variables of MetSy in diabetic participants. Blood pressure and anthropometric measurements such as waist circumference (WC) and body mass index (BMI) were measured. Fasting venous blood was collected to analyze biochemical variables such as fasting blood sugar (FBS), TG, and high-density lipoprotein-cholesterol (HDL-C). The microvascular complications of T2DM were established using fundus ophthalmoscopy and neurological and kidney function assessments with the help of laboratory tests. These variables were matched between MetSy and no MetSy groups along with the presence or absence of diabetes microvascular complications. This information was analyzed based on these assessments and patient interviews. Results Of the 160 T2DM patients, the mean age was 52 years with a predominance of females (51.8%) in the 50-59-year age group (56.8%). The average BMI for females was 29.38 ± 0.54 kg/m², and 32 (20%) had obesity. Females exhibited a large WC of 93.52 ± 1.58 cm, and 48 of 83 females had reported diabetes microvascular complications. A significant p-value was observed for hypertension, high TG, low HDL-C, large WC, obesity, BMI, age, and female gender on comparing diabetics with metabolic syndrome (MetSy+) and those without metabolic syndrome (MetSy-). The prevalence of microvascular complications in T2DM patients with MetSy+ was 52.5% compared with 47.5% in MetSy-. The prevalence of diabetic retinopathy was 24.9% (95% confidence interval (CI) = 20.3%-29.6%), nephropathy was 16.8% (95% CI = 12.8%-20.7%), and neuropathy was 10.8% (95% CI = 7.4%-13.3%). Conclusions The prevalence of MetSy observed among T2DM patients was 65%, with married obese females in the 50-59-year age group being more likely to be affected than males. Hypertension, poor glycemic control, high TG, low HDL-C, and greater anthropometric waist measurements and BMI were additional risk factors that tended to increase the MetSy burden in T2DM. Diabetic retinopathy, nephropathy, and neuropathy were the most prevalent microvascular complications of diabetes, and immediate attention is needed to stop their detrimental effects. Longer uncontrolled diabetes, increasing age, and hypertension were independent predictors of microvascular complications. To further reduce the risks of complications that threaten healthy aging and prognosis for these patients, MetSy screening, health education, and better diabetic management are crucial.

Correction: Superior Mesenteric Artery Syndrome: Delayed Diagnosis of a Rare Clinical Entity With a Common Clinical Presentation.

[This corrects the article DOI: 10.7759/cureus.26728.].

Superior Mesenteric Artery Syndrome: Delayed Diagnosis of a Rare Clinical Entity With a Common Clinical Presentation.

Superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, is an uncommon disorder that involves a set of symptoms that primarily includes postprandial pain at times associated with intestinal obstruction. Although a rare disease in the general population, SMA syndrome has a high probability of occurrence in patients who are severely malnourished or have certain debilitating conditions leading to a loss of retroperitoneal fat. Here, we present the case of a 16-year-old male with a one-year history of postprandial abdominal pain associated with nausea, multiple episodes of vomiting, and abdominal distension. Amid a delayed diagnosis and multiple hospital visits, the patient's condition further deteriorated. Thereafter, computed tomography of the abdomen confirmed this rare diagnosis. Because the patient could not be further managed conservatively, laparoscopic duodenojejunostomy was planned and done. This case report highlights the various challenges in diagnosing this disease and highlights the importance of an early diagnosis so that patients can be managed effectively and timely.

MR Product as a Novel Diagnostic Indicator for Chronic Secondary Mitral Regurgitation.

Background Chronic secondary mitral regurgitation (SMR) is a common form of valvular heart disease. Its diagnosis through echocardiography is challenging and dependent on subjective interpretations. The subjective error to diagnose SMR can be reduced by developing accurate predictive quantitative parameters that support echocardiographic interpretations and clinical manifestations. The present study aims to develop a new diagnostic indicator for chronic SMR. The new indicator called MR product is the product of left atrial diameter (LAD) and left ventricular internal dimension at end-systole (LVIDs). Materials and Methods An analytical, case-control study was conducted from transthoracic echocardiography (TTE) reports of 720 patients performed according to the guidelines of the American Society of Echocardiography. The LAD and LVIDs were measured using the standard M Mode TTE. Out of the 720 patients who underwent TTE, 300 patients were diagnosed with chronic SMR by experienced clinicians. Only 115 of those 300 patients met the inclusion criteria for chronic SMR.  Results The MR product was significantly associated with chronic SMR (rho = 0.83) and predicted it with an odds ratio of 1.014 (p < 0.001). The MR product was able to diagnose SMR with a sensitivity of 94.8% and a specificity of 92.2%, respectively, for a cut off value of 1,045 mm2. Conclusion A new parameter called MR product (LAD multiplied with LVIDs) has very high sensitivity and specificity for SMR. Therefore, it can aid in establishing its diagnosis, along with other diagnostic modalities. The new parameter may also potentially increase the diagnostic accuracy of the disease.

Urachal Sinus Complicated by an Umbilical Abscess.

The urachal sinus is a vestigial remnant that ensues in the aftermath of incomplete obliteration of the embryonic urachus. Urachal sinuses often remain asymptomatic, being discovered incidentally in instances where they are complicated with a superimposed infection or abscess. Due to their rare occurrence in adults, urachal sinuses are rarely included in the list of differential diagnosis surrounding umbilical pain in adult patients. We hereby delineate a unique case of a urachal sinus in a 26-year-old male patient. Due to the presence of an abscess in a hirsute male, a presumptive diagnosis of an umbilical pilonidal sinus was suspected. However, further diagnostic workup divulged an unequivocal diagnosis of a urachal sinus complicated by an abscess formation.

Relationship of left ventricular and atrial dimensions with moderate to severe left ventricular diastolic dysfunction (grade II and above).

INTRODUCTION: Left ventricular diastolic dysfunction (DD) is an entity in which the ventricle fails to fill up properly due to impaired ventricular relaxation and/or decreased compliance. The diagnosis of diastolic dysfunction is based on a variety of parameters in doppler echocardiograpy. However, some parameters like interventricular septal thickness in diastole (IVSd), posterior wall thickness in diastole (PWd), left ventricular internal end diastolic and systolic diameters (LVIDD and LVISD) along with left atrial diameters (LAD) have yet to be evaluated for the diagnostic workup of DD. METHODS: A case control study was done in the cardiology department from patient records from 2016 to 2018. Patients were diagnosed as diastolic dysfunction grade II and above by doppler echocardiography. IVSd, PWd, LVIDD, LAD, LVISD were obtained through 2-D echocardiography. RESULTS: Patients with DD had greater LAD, IVSd and PWd and decreased LVIDD and LVISD as compared to control group. Overall, IVSD was the most significant predictor (OR 1.52 95%CI 1.35-1.71) of DD followed by PWd and LAD. Similarly, LAD, IVSd and PWd had higher sensitivity and specificity than LVIDD and LVIDS. CONCLUSION: IVSd, LAD and PWd showed significant performance in the diagnosis of diastolic dysfunction and hence can be used as a screening and diagnostic tool in diastolic dysfunction of grade ll and above.