Evaluation of cytokine gene expression in psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory disease affecting the skin with an unclear etiological significance. AIM: In this study, we determined the mRNA expression and circulating levels of T helper (Th)/T regulatory (Treg) cytokines in psoriasis and analyzed their association with disease severity and treatment response. MATERIAL AND METHODS: 189 psoriasis patients and 189 controls were recruited. Circulating Th/Treg cytokines (IL-12, IFN-γ, IL-17, IL-23, TGF-ß and IL-4) were measured at baseline and at follow-up after 12 weeks of methotrexate treatment by ELISA and their relative mRNA expression at baseline was estimated by quantitative PCR. RESULTS: We observed increased levels of Th1/Th17 cytokines (IFN-γ, IL-17, IL-12 and IL-23) and a decrease in levels of Th2/Treg cytokines (IL-4 and TGF-ß) in psoriasis patients at baseline, as compared to controls. Further, we observed that there was a significant decrease in Th1/Th17 cytokines, whilst Th2/Treg cytokine levels were significantly increased on follow-up after treatment with systemic metho trexate, as compared to pre-treatment levels. Our results were further confirmed by the significantly higher mRNA expression of Th1/Th17 cytokine genes and significantly lower mRNA expression of Th2/Treg cytokine genes in patients with psoriasis, as compared to controls. A significant positive correlation of Th1/Th17 cytokines was observed with disease severity in cases, whilst Th2/Treg cytokines correlated negatively with disease severity. CONCLUSIONS: Our results show that increased Th1/Th17 cytokines and decreased Th2/Treg cytokines, both at the circulatory and gene expression level, play an important role in the immunopathogenesis and severity of psoriasis.

Temporal expression of genes involved in folate metabolism and transport during placental development, preeclampsia and neural tube defects.

Folate is an essential micronutrient during pregnancy. The differential expression of genes related to folate transport and metabolism during the advancing gestation and pregnancy complications is not well established. Hence, we studied the gene expression of folate metabolism and transport proteins in the placenta with advancing gestation, preeclampsia and neural tube defects (NTD). The expression of folate transporters and enzymes involved in folate metabolism in the placenta with advancing gestation and pregnancy-related disorders were studied by 2-step RT-PCR. Folate levels were estimated by microbiological assay using Lactobacillus casei. Significant changes in levels of placental folate metabolizing enzymes were found in both physiological and pathological pregnancies during advancing gestation. Expression of methyltetrahydrofolate reductase (MTHFR) (p < 0.001) and cystathionine-ß-synthase (CBS) (p < 0.001) was decreased while that of methionine synthase (MS) (p < 0.001) was increased with advancing gestation. A much-reduced expression of MTHFR (p < 0.01) and an abnormally high expression of methionine synthase reductase (p < 0.001) were observed in the NTD group. In NTDs, there was an adaptive up-regulation of folate transporters mainly reduced folate carrier (p < 0.001) and folate receptor alpha (p < 0.001). MTHFR expression showed a strong positive correlation (r = 0.96, p < 0.01) with folate levels in placenta. Pregnant women with preeclampsia had low expression of MS (p < 0.01) in association with low folate levels. Placental folate metabolizing enzymes exhibited a differential pattern during advancing gestation. Deficient folate status in association with alteration in expression of enzymes involved in folate metabolism might be associated with pregnancy complications such as preeclampsia and NTDs.

Evaluating the Diagnostic Potential of Serum Vascular Endothelial Growth Factor and Adiponectin in Diabetic Peripheral Neuropathy.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) presents a formidable health challenge in type 2 diabetes mellitus (T2DM) patients. This study in eastern Uttar Pradesh aims to assess the roles of vascular endothelial growth factor (VEGF) and adiponectin in DPN, recognizing the crucial need for understanding its molecular underpinnings for enhanced diagnosis and management. METHODS: In a cross-sectional study analyzing clinical and biochemical data, 86 individuals aged 35 to 65 years were examined, including 43 with neuropathy and 43 without. Neuropathy assessment included the neuropathy symptom score (NSS), diabetes neuropathy examination (DNE) score, and nerve conduction studies. Levels of VEGF and adiponectin were correlated with motor nerve amplitude, NSS, and DNE scores. Receiver operating characteristic (ROC) curve analysis gauged diagnostic potential, and logistic regression assessed predictors for DPN. RESULTS: Patients with neuropathy exhibited significantly elevated VEGF levels compared to those without, while adiponectin showed no significant difference. VEGF demonstrated a negative correlation with motor nerve amplitude and a positive correlation with NSS and DNE scores. ROC analysis revealed strong diagnostic capability for VEGF (area under the curve: 0.807). NSS and DNE scores indicated good and moderate diagnostic accuracy, respectively. In logistic regression analysis, VEGF emerged as the sole significant predictor (odds ratio: 1.11, 95% CI (1.03, 1.20), p = 0.0092). CONCLUSION: Findings suggest VEGF's potential as a biomarker for diagnosing DPN in T2DM, associated with neuropathy severity. Adiponectin showed no significant association. The study underscores NSS and DNE scores' therapeutic relevance as valid neuropathy assessment tools.

The Prognostic Value of De Ritis Ratio on the Survival Rate of ICU-Admitted COVID-19 Patients During the Second Wave: A Retrospective Study in a Tertiary Care Hospital in India.

Background Prognostic markers are essential for optimizing COVID-19 patient care. This retrospective study examines the prognostic value of the De Ritis ratio (DRR) in intensive care unit (ICU)-admitted patients during the second wave of the pandemic. Methods A retrospective study of four-month duration (March to June 2021) was conducted on 161 ICU-admitted COVID-19 patients in a tertiary care hospital in India. The data included demographics, comorbidities, laboratory results, ICU admission dates, and survival outcomes. The De Ritis ratio was calculated on day 0, day 2, and day 5. The analyses included descriptive statistics, diagnostic accuracy, and logistic regression. Results Survival rates decreased with ICU stay: day 0 (survival, 58.4%; mortality, 41.6%), day 2 (survival, 54.5%; mortality, 45.5%), and day 5 (survival, 49.5%; mortality, 50.5%). De Ritis ratio's diagnostic accuracy varied, with increasing specificity and negative predictive value (NPV). Logistic regression showed higher day 5 De Ritis ratios, and male gender was associated with reduced survival odds. Conclusion The De Ritis ratio demonstrates promise as an early prognostic marker for COVID-19 patients, with an increase in predictive accuracy over time. The results emphasize the De Ritis ratio's potential as an early indicator of disease severity, offering clinicians a tool to recognize patients at higher risk and enhance the effectiveness of critical care interventions.

Evaluating the Effectiveness of Online Assessments and Their Parameters as Predictors of Academic Performance in Undergraduate Medical Education.

Background and objectives Considering the increasing utilization of online educational tools in medical education, it is essential to evaluate the reliability and validity of online assessments to accurately assess student proficiency and predict academic success. This study investigated the predictive efficacy of different online assessment methods in comparison to standard offline methods within the medical educational setting. Methods This study utilized a mixed-methods crossover design, involving 125 first-year medical students who were randomly assigned to either online or traditional examinations. The students then crossed over to the other type of assessment. The assessments consisted of multiple-choice questions (MCQs), viva voce, objective structured clinical examinations, and written theory examinations. Quantitative data on results, finishing times, and academic metrics were analyzed, along with qualitative data from student interviews exploring perceptions of each format. Results The online MCQs had the highest average scores and a moderately positive correlation with performance on the theory examination (r=0.326). Regression models indicated that online and offline MCQs were moderate positive predictors of theoretical marks (R2=0.106 and 0.107, respectively). Qualitative responses emphasized advantages such as flexibility and accessibility for online examinations but also concerns regarding technological challenges, interaction, and integrity compared to traditional formats. Conclusions Online MCQ assessments showed promise as indicators of medical student academic performance. However, additional online forms require improvement to match conventional assessments reliably. As medical education involves digital technologies, cautious implementation of online evaluations substantiated by further research is needed to preserve educational quality standards.

Evaluating Interference of Lipemia on Routine Clinical Biochemical Tests.

Objective Lipemia is an important cause of preanalytical errors in laboratory results. They affect the specimen integrity and trustworthiness of laboratory results. The present study was to assess the impact of lipemia on routine clinical chemistry analytes. Methods Anonymous leftover serum samples with normal levels of routine biochemical parameters were pooled. Twenty such pooled serum samples were used for the study. The samples were spiked with commercially available intralipid solution (20%) to produce lipemic concentrations of 0, 400 (mild, 20 µL), 1,000 (moderate, 50 µL), and 2,000 mg/dL (severe, 100 µL). Glucose, renal function test, electrolytes, and liver function test were estimated in all the samples. Baseline data without the effect of interference was considered as true value and percentage bias for the spiked samples was calculated. Interference was considered significant if the interference bias percentage exceeded 10%. Result Parameters like glucose, urea, creatinine, direct bilirubin, sodium, potassium, and chloride showed negative interference at mild and moderate lipemic concentration and positive interference at severe lipemic concentration. Parameters like aspartate transaminase (AST) and alanine transaminase (ALT) showed negative interference at mild and positive interference at moderate and severe lipemic concentration. Whereas uric acid, total protein, albumin, total bilirubin, alkaline phosphatase, gamma-glutamyl transferase, calcium, magnesium, and phosphorous showed positive interference at all concentrations. Significant interference (> 10%) was shown for magnesium (mild lipemia), albumin, direct bilirubin, ALT, and AST at moderate lipemic concentration. All parameters showed significant interference at severe lipemic concentration. Conclusion All the study parameters are affected by lipemic interference at varying levels. Laboratory-specific data regarding lipemic interference at various concentrations on the clinical biochemistry parameters is needed.

Role of Selective Serotonin Reuptake Inhibitors in the Treatment of Hypochondriasis: A Systematic Review.

Hypochondriasis is a condition characterized by an unrealistic fear of having a serious medical illness resulting in health anxiety. Currently, no evidence-based pharmacological treatment options are available for the treatment of hypochondriasis. Since selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment option for anxiety disorders, they may be useful for relieving hypochondriasis symptoms. Moreover, off-label use of SSRIs in these cases is highly prevalent in clinical practice. Thus, in this study, we aimed to review the available literature to assess the role of SSRIs in the treatment of hypochondriacal symptoms. A systematic search was conducted in PubMed, Scopus, ScienceDirect, Embase, and Cochrane Database of Systematic Reviews from the date of inception to December 2022. We included only randomized clinical trials (RCTs) investigating the effect of SSRIs in the treatment of hypochondriacal symptoms. Non-RCTs, observation studies, and animal studies were excluded. The Risk of Bias 2 tool was used to assess the quality of included studies. Out of 2264 articles, six RCTs met our inclusion criteria. Studies have been conducted using different SSRIs in the treatment of primary hypochondriasis and hypochondriacal symptoms associated with other psychiatric disorders. All the studies have found that the use of SSRIs has some beneficial role in improving hypochondriacal symptoms. This suggests that SSRIs may be one of the promising pharmacological interventions in the treatment of hypochondriasis.

Unraveling the Role of Tumor Necrosis Factor-Alpha in Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is a prevalent and debilitating complication of diabetes mellitus, leading to sensory abnormalities, decreased balance, and increased risk of foot problems. Although tumor necrosis factor-alpha (TNF-α) has emerged as a potential factor in the pathogenesis of DPN, its role remains contested. This study intends to thoroughly analyze the association between TNF-α and DPN by combining data from various global studies. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included 23 articles investigating TNF-α levels in DPN patients for systematic review and 11 articles for meta-analysis. Data were extracted, and heterogeneity was examined. A random-effect model was chosen due to high heterogeneity. The major outcome measure across studies was serum TNF-α levels. The meta-analysis found a significant mean difference of 15.2464 (95% confidence interval = 4.4963; 25.9965) under the random-effect model due to the substantial heterogeneity (I2 = 98.1%) among included studies. The meta-analysis indicates a consistent elevation in TNF-α levels in individuals with DPN compared to those without neuropathy. This underlines the potential of TNF-α as a biomarker and contributor to diabetic neuropathy. Despite heterogeneity, the study's extensive scope and systematic approach enhance the trustworthiness and generalizability of the findings.

Role of Melatonin in the Management of Substance Addiction: A Systematic Review.

Recent evidence links melatonin hormone and its receptor to the etiology and behavioral manifestation of addiction. The role of exogenous melatonin in addiction treatment is still inconsistent and unclear. The present study aimed to review the literature on randomized clinical trials that evaluated the role of melatonin supplementation, compared to placebo, in the treatment of various substance addictions. The literature searches of relevant articles published in the English language in MEDLINE and Google Scholar databases were performed from inception up to May 2021. We included only randomized clinical trials investigating the effect of melatonin treatment, compared to placebo, on substance addiction-related parameters. Non-randomized clinical trials, observation studies, and animal studies were excluded. The risk of bias-2 was used to assess the quality of the studies. Of 537 articles, 12 randomized control trials (RCT) met our inclusion criteria. Studies have been conducted on substances of addiction including benzodiazepine (BZD), alcohol, nicotine, and opioids. Our results indicated that melatonin treatment had mixed results in improving sleep quality and was not found beneficial in BDZ cessation/discontinuation rate among patients with BDZ dependence. Sleep quality and mental health had improved by melatonin supplements in opioid addiction. In nicotine addiction, melatonin treatment showed effectiveness only on mood changes but not in performance tests. In patients with alcohol use disorder (AUD), melatonin treatment did not show any improvement in sleep quality. We found that the use of exogenous melatonin in substance addiction has mixed results which do not provide sufficient evidence, relative to randomized clinical trials, to establish its role.

Burden of diabetic kidney disease among persons with type 2 diabetes mellitus registered in a tertiary care center, Puducherry.

BACKGROUND & AIMS: To determine burden of diabetic kidney disease (DKD) and estimate yield and number needed to screen (NNS) in a tertiary diabetes care center. METHODS: DKD was diagnosed if estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 or Urinary Albumin Creatinine Ratio (UACR) ≥30 mg/g in two urine samples. RESULTS: Of 511 participants, 206 (40%) had DKD. Using both UACR and eGFR, yield and NNS were 39% and three, respectively. CONCLUSION: Using eGFR alone, yield and NNS to find a case of DKD among consecutive adult (≥18 years age) patients with type 2 diabetes mellitus were 26.4% and 4, respectively.

Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs.

DNA methylation, a central component of the epigenetic network is altered in response to nutritional influences. In one-carbon cycle, folate acts as a one-carbon carrier and vitamin B12 acts as co-factor for the enzyme methionine synthase. Both folate and vitamin B12 are the important regulators of DNA methylation which play an important role in development in early life. Previous studies carried out in this regard have shown the individual effects of these vitamins but recently the focus has been to study the combined effects of both the vitamins during pregnancy. Therefore, this study was planned to elucidate the effect of the altered dietary ratio of folate and B12 on the expression of transporters, related miRNAs and DNA methylation in C57BL/6 mice. Female mice were fed diets with 9 combinations of folate and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks post-weaning. Maternal and fetal (F2) tissues were collected at day 20 of gestation. Deficient state of folate led to an increase in the expression of folate transporters in both F1 and F2 generations, however, B12 deficiency (BDFN) also led to an increase in the expression in both the generations. B12 transporters/proteins were found to be increased with B12 deficiency in F1 and F2 generations except for TC-II in the kidney which was found to be decreased in the F1 generation. miR-483 was found to be increased with all conditions of folate and B12 in both F1 and F2 generations, however, deficient conditions of B12 led to an increase in the expression of miR-221 in both F1 and F2 generations. The level of miR-133 was found to be increased in BDFN group in F1 generation however; in F2 generation the change in expression was tissue and sex-specific. Global DNA methylation was decreased with deficiency of both folate and B12 in maternal tissues (F1) but increased with folate deficiency in placenta (F1) and under all conditions in fetal tissues (F2). DNA methyltransferases were overall found to be increased with deficiency of folate and B12 in both F1 and F2 generations. Results suggest that the dietary ratio of folate and B12 resulted in altered expression of transporters, miRNAs, and genomic DNA methylation in association with DNMTs.

Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy.

AIMS: Diabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR. MATERIALS AND METHODS: Our study comprised of 2 groups of 41 each. Group A (cases) included T2DM patients with retinopathy and Group B (controls) included T2DM patients without retinopathy. Routine parameters, mainly, fasting blood glucose, and lipid profile were measured using autoanalyzer. Serum MMP-9, TIMP-1, and insulin levels were assessed using ELISA method. RESULTS AND CONCLUSION: Statistically significant increase in the levels of MMP-9, insulin, fasting blood glucose and lipid profile were observed in the serum of T2DM patients with retinopathy, as compared with those without retinopathy. These results help to conclude that rise in MMP-9, and associated serum markers promote disease progress in DR. These findings suggest that the elevations of our study markers in the serum of the type 2 diabetic patients with retinopathy, as compared to those without retinopathy, play important roles in aggravating tissue matrix degradation, supporting DR disease progression.

Association Between Adiponectin and Insulin Resistance in Diabetic Urolithiasis.

OBJECTIVES: The prevalence of urolithiasis is increasing worldwide. Diabetes mellitus (DM) is characterized by insulin resistance, which increases the risk of kidney stone formation. Adiponectin is an insulin-sensitizing and anti-inflammatory cytokine, which is known to improve glucose tolerance and insulin resistance in humans. The association of insulin and adiponectin with kidney stones is not clear. Hence, the present study aim to assess the serum levels of adiponectin and insulin resistance in DM patients with urolithiasis in comparison to those without. METHODS: This study involved two groups, group A consisted of 30 patients with DM and urolithiasis, and group B consisted of 30 patients with DM but without urolithiasis (control group). Biochemical parameters studied were serum adiponectin, insulin, glucose, urea, creatinine, and 24 hours urinary calcium and phosphate. RESULTS: The serum adiponectin level was significantly increased in the diabetic urolithiasis cases (group A) compared to the control group (group B). The levels of 24 hours urine calcium and phosphorus were also significantly increased in group A. There was no significant difference in serum insulin and homeostasis model assessment of insulin resistance between the two groups. A negative correlation was seen between serum adiponectin and insulin among the cases (r = -0.368 and p = 0.045). CONCLUSIONS: We found that serum adiponectin levels are increased in patients with DM and urolithiasis.