A randomized clinical trial investigating the impact of magnesium supplementation on clinical and biochemical measures in COVID-19 patients.

BACKGROUND: This study sought to examine the impact of magnesium supplementation on clinical outcomes and biochemical factors among hospitalized patients with COVID-19. METHODS: This double-blind, randomized clinical trial was conducted at Razi Hospital, Ahvaz, Iran, between September 2021 and March 2022. Participants aged 18-70 years with moderate disease severity were enrolled. Magnesium supplementation (300 mg daily) was administered to the intervention group, while the control group received a placebo. Clinical outcomes, including the need for oxygen therapy, oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health, were assessed. Blood samples were collected to measure biochemical variables. RESULTS: The main result was the count of individuals requiring oxygen therapy. Additional outcomes comprised of oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health. Out of 64 participants, 60 completed the study. The results showed that magnesium supplementation significantly reduced the number of patients requiring oxygen therapy (9 vs. 14; P < 0.001). Moreover, the magnesium group demonstrated improved oxygen saturation compared to the control group (4.55 ± 2.35 vs. 1.8 ± 1.67; P < 0.001). Furthermore, we observed a noteworthy enhancement in the quality of life and depression score in the magnesium group. No significant differences were observed in respiratory rate, fever, hs-CRP, and TNF-α levels (P > 0.05). CONCLUSION: The findings suggest that magnesium supplementation may have beneficial effects on clinical outcomes and arterial oxygen saturation in COVID-19 patients. More investigation is necessary to delve into its potential mechanisms and long-term effects on patient outcomes. TRIAL REGISTRATION: This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20210413050957N1. (The registration date: May 1, 2021).

The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population.

BACKGROUND: To investigate the genetics of early-onset progressive cerebellar ataxia in Iran, we conducted a study at the Children's Medical Center (CMC), the primary referral center for pediatric disorders in the country, over a three-year period from 2019 to 2022. In this report, we provide the initial findings from the national registry. METHODS: We selected all early-onset patients with an autosomal recessive mode of inheritance to assess their phenotype, paraclinical tests, and genotypes. The clinical data encompassed clinical features, the Scale for the Assessment and Rating of Ataxia (SARA) scores, Magnetic Resonance Imaging (MRI) results, Electrodiagnostic exams (EDX), and biomarker features. Our genetic investigations included single-gene testing, Whole Exome Sequencing (WES), and Whole Genome Sequencing (WGS). RESULTS: Our study enrolled 162 patients from various geographic regions of our country. Among our subpopulations, we identified known and novel pathogenic variants in 42 genes in 97 families. The overall genetic diagnostic rate was 59.9%. Notably, we observed PLA2G6, ATM, SACS, and SCA variants in 19, 14, 12, and 10 families, respectively. Remarkably, more than 59% of the cases were attributed to pathogenic variants in these genes. CONCLUSIONS: Iran, being at the crossroad of the Middle East, exhibits a highly diverse genetic etiology for autosomal recessive hereditary ataxia. In light of this heterogeneity, the development of preventive strategies and targeted molecular therapeutics becomes crucial. A national guideline for the diagnosis and management of patients with these conditions could significantly aid in advancing healthcare approaches and improving patient outcomes.

Kidney stones and dietary intake in adults: a population-based study in southwest Iran.

BACKGROUND: The prevalence of kidney stones is on the rise globally. Several risk factors, including lifestyle, contribute to the formation of kidney stones. Nevertheless, there is a contentious debate about the relationship between diet and kidney stones. Therefore, our study aimed to assess the relationship between macronutrients and micronutrients and the formation of kidney stones. METHODS: This population-based cross-sectional study was conducted in the baseline phase of the Hoveyzeh Cohort Study, focusing on adults aged 35-70 in southwest Iran. The information on demographic characteristics, anthropometrics, kidney stone history, and food frequency was collected. Chi-square and t-tests were utilized to assess the relationship between categorical and numerical variables with kidney stones. The ANCOVA and logistic regression models were used to evaluate the relationships while controlling for confounding factors. RESULTS: Among 10,009 participants, the overall prevalence of kidney stones was 18.77% (95% CI: 17.99-19.53). A higher intake of carbohydrates [OR = 1.02 (95% CI:1.002-1.03), p = 0.026] and copper [OR = 1.04 (95% CI:1.01-1.09), p = 0.025] were found to be associated with kidney stones. No associations were found between the other assessed macronutrients or micronutrients and kidney stones (p-tvalues > 0.05). CONCLUSION: Our study's findings indicate a correlation between diet and the formation of kidney stones. However, the relationship between dietary factors and kidney stones is complex, and further research is needed.

Impact of Ramadan fasting on lipid profile, uric acid, and HbA1c in CKD: A systematic review and meta-analysis.

Studies have shown that fasting during Ramadan has different effects on circulating levels of several biochemical markers. This study aims to conduct a comprehensive evaluation of studies related to the effect of fasting in the holy month of Ramadan on lipid profile, uric acid, and HbA1c in CKD patients. Studies were systematically searched and collected from three databases (PubMed, Scopus, and Web of Science). After screening, the quality and risk of bias assessment of the selected articles were evaluated. Study heterogeneity was assessed using the Cochrane test and I² statistic. In case of any heterogeneity random effects model with the inverse-variance method was applied. All analyses were performed using STATA software version 16. Four observational studies were included in this study. The results of this meta-analysis were that cholesterol (Weighted mean differences (WMD):0.21 with 95% CI:-0.09-0.51 (P-value=:0.18)), LDL (WMD:0.06 with 95% CI -0.24-0.36 (P-value:0.69)), triglyceride (WMD:0.05 with 95% CI:-0.25-0.35 (P-value:0.73)) had not-significant increase. Uric acid (WMD: -0.11 with 95% CI: -0.42-0.21 (P-value:0.51)) and HbA1c (WMD: -0.22 with 95% CI: -0.79-0.36 (P-value: 0.46)) show a non-significant decrease. The results of the analyses did not report significant changes in the lipid profile, uric acid, and HbA1c in CKD patients after Ramadan fasting.

The Protective Effects of Syringic Acid on Bisphenol A-Induced Neurotoxicity Possibly Through AMPK/PGC-1α/Fndc5 and CREB/BDNF Signaling Pathways.

Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200 mg/kg) and SA (50 mg/kg) for 21 days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200 mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aß, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50 mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aß proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.

The effect of soy isoflavones on non-alcoholic fatty liver disease and the level of fibroblast growth factor-21 and fetuin A.

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Subjects were randomized to either receive two tablets of soy isoflavone (100 mg/day) or placebo. At week 12, the serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and controlled attenuation parameter (CAP) score were significantly decreased only in the soy isoflavone group (P < 0.05). A significant decline in the gamma glutamyl transferase (GGT) level was observed only in the placebo group (P = 0.017). A significant increase in the serum level of fetuin A was shown in both groups at the end of the trial with a significantly greater increment in the soy isoflavone group compared to the placebo group (P < 0.05). The changes in the serum level of FGF-21 were not significant in any of the two groups. Steatosis grade significantly improved only in the soy isoflavone group (P = 0.045). There was no significant change in the fibrosis grade in the groups. Soy isoflavone intake led to a decrease in ALT, AST, CAP score, steatosis grade and an increase in the level of fetuin A. However, no significant changes were observed in the fibrosis grade and serum levels of GGT and FGF-21.

Polyphenol consumption and Nonalcoholic fatty liver disease risk in adults.

In this cross-sectional investigation, the primary objective was to explore the correlation between the consumption of polyphenols and the likelihood of non-alcoholic fatty liver disease (NAFLD) in the adult population participating in the Hoveyzeh cohort. Data from the Hoveyzeh cohort study, part of the Persian Cohort Study, involving 10,009 adults aged 35-70, were analyzed. Exclusions were made for missing data, extreme energy intake, and liver cancer patients. Dietary habits were assessed using a food frequency questionnaire, and polyphenol intake was calculated using the Phenol Explorer database. Logistic regression analyses, adjusted for confounders, were performed to assess the relationship between polyphenol subclasses (total polyphenols, total flavonoids, phenolic acid, and lignin) and NAFLD. Among 9894 participants, those in the highest quintile of total polyphenol (OR 0.65, CI 0.5-0.84; P = 0.007), phenolic acid (OR 0.67, CI 0.52-0.86; P < 0.001), and lignin intake (OR 0.69, CI 0.52-0.87; P = 0.001) demonstrated lower odds of NAFLD compared to the lowest quintile, even after adjusting for confounding factors. However, no significant association was found between total flavonoid intake and NAFLD (OR 1.26, CI 0.96-1.67; P = 0.47). Subgroup analysis indicated a significant inverse association between total polyphenols and NAFLD in women (OR 0.64, CI 0.42-0.93; P = 0.001). Higher intake of total polyphenols, phenolic acid, and lignin was associated with reduced odds of NAFLD among adults in the Hoveyzeh cohort. This suggests that dietary patterns rich in these polyphenols may play a role in mitigating the risk of NAFLD. Further interventional and longitudinal studies are needed to validate these findings and explore potential preventive strategies involving polyphenol-rich diets.

Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma.

Given the numerous adverse effects of lung cancer treatment, more research on non-toxic medications is urgently needed. Curcumin (CUR) and berberine (BBR) combat drug resistance by controlling the expression of multidrug resistant pump (MDR1). Fascinatingly, combining these medications increases the effectiveness of preventing lung cancer. Their low solubility and poor stability, however, restrict their therapeutic efficacy. Because of the improved bioavailability and increased encapsulation effectiveness of water-insoluble medicines, surfactant-based nanovesicles have recently received a great deal of attention. The current study sought to elucidate the Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma. The impact of several tween (20, 60, and 80) types with varied hydrophobic tails on BBR/CUR-TNV was evaluated. Additionally, the MDR1 activity and apoptosis rate of the BBR/CUR-TNV combination therapy were assessed. The encapsulation effectiveness of TNV was affected by the type of tween. With the TNV made from tween 60, cholesterol, and PEG (47.5: 47.5:5), more encapsulation effectiveness was attained. By combining CUR with BBR, especially when given in TNV, apoptosis increased. Additionally, when CUR and BBR were administered in combination, they significantly reduced the risk of MDR1 development. The current work suggests that the delivery of berberine and curcumin as a combination medication therapy via tween-based nanovesicles may be a potential lung cancer treatment.

PERCHING syndrome caused by variant gene KLHL7 in the first Iranian patient: a case report study.

Introduction and importance: PERCHING syndrome is a condition that affects many parts of the body and is caused by genes passed down from both parents. People with this syndrome have delays in their development, unusual facial features, trouble eating and breathing, slow overall growth, weak muscles, and stiff joints. Case presentation: The child at the age of 6 months suffered from developmental delay, delayed walking, speech delay, and hypotonia and was referred to the Neurologist. Also, he has an abnormal phenotype. Whole-exome sequencing (WES) revealed a missense variant in the KLHL7 gene at a highly conserved genomic Chr7: 23124718T>G; NM_018846:exon3:c.110T>G:p.Val37Gly. Clinical discussion: One way to explain the difference in physical characteristics caused by recessive KLHL7 mutations might be related to the person's genetic makeup. However, the genes someone has do not always accurately determine their physical traits. Conclusion: This report will help us learn more about the different traits and characteristics of Perching syndrome. The authors need to do more research on how proteins work and study more about patients with different characteristics to fully understand this.

Dietary insulin index, dietary insulin load and dietary patterns and the risk of metabolic syndrome in Hoveyzeh Cohort Study.

Postprandial insulin secretion has been associated with metabolic disorders such as hyperlipidemia and type 2 diabetes. Therefore, we aimed to explore the relationship between dietary insulin indices and dietary pattern with the risk of Metabolic Syndrome (MetS). The participants of the present cross-sectional study were included among the individuals who participated in the Hoveyzeh Cohort Study (HCS). A total of 3905 Iranian adults, aged 35-70 years, are included in the current analysis. The Food Frequency Questionnaire (FFQ) is used to calculate the dietary Insulin Index (DII), Insulin Load (DIL), and dietary pattern. Dietary pattern was derived using Reduced-Rank Regression (RRR) based on intake of protein (g/day), fiber (g/day), fat (g/day), magnesium (mg/day), and dietary insulin index were considered as response variables. The Generalized Linear Model was used to obtain the odds ratio (OR) and 95% confidence interval (CI) for MetS based on gender, while considering quartiles of DIL, DII scores, and dietary pattern, adjusted for potential confounders. The mean ± SD of age and BMI of the participants in the top quartile of DIL were 45.72 ± 8.05 years and 28.25 ± 5.02 kg/m2, respectively. The mean ± SD of DII was 40.53 ± 4.06 and the mean ± SD of DIL was 117,986.1 ± 30,714.06. A significant positive association was observed between DIL and MetS in women after adjusting for confounding factors (OR: 1.51; 95% CI 1.16; 1.96). No significant association was seen between DIL, DII, and MetS among men. A derived dietary pattern characterized by high intakes of fruits, sugar, sweet deserts, Whole Grains, and dairy was associated with an increased risk of MetS in adjusted model2 among women (OR: 1.41; 95% CI 1.13; 1.75) and men in the same model (OR: 2.09; 95% CI 1.35; 3.21).However, the final model was significant just for men (OR: 2.08; 95% CI 1.35; 3.21) and not for women (OR: 1.24; 95% CI 0.96; 1.60). Our findings showed that adherence to a diet with a high insulin load can increase the risk of MetS in women. In addition, a derived dietary pattern by RRR indicated that a diet rich in fruits, sugar, sweet deserts, whole Grains, and dairy is related to increased risk of MetS in both men and women.

Tumor Necrosis Factor Alpha (TNFα) Gene Promoter Polymorphisms and Haplotypes are Associated with the Febrile Seizure (FS) and TNFα Serum Levels.

Objectives: Febrile seizure (FS) is a neuroinflammatory disease involving fever-induced seizures affecting children in the early stages of life. TNFα is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNFα could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNFα variants, including TNFα -238 G/A (rs361525), TNFα -308 G/A (rs1800629), and TNFα -376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNFα serum levels in an Iranian population. Materials & Methods: Sixty-eight FS patients and 136 controls were enrolled. The SSP-PCR method was utilized to analyze TNFα promoter genotypes. This research also confirmed the genotyping results by sequencing samples of ten patients and normal controls. Results: The GG genotype of -238 SNP was associated with the increased risk of FS [OR = 12.65, 95% CI (2.83-56.60), P-value = 0.0012]. The AA genotype in the-308 region was increased in patients with FS and associated with the disease [OR = 4.62, 95% CI (1.46-14.56), P-value = 0.028]. The increased occurrence of heterozygous AG in the -376 SNP among control groups has been linked to a decreased risk of FS [OR = 0.22, 95% CI (0.11-0.43), P-value = 0.0001]. This study revealed that AGA (-238/ -308/ -376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (-238/ -308/ -376) carriers were more susceptible to FS. Conclusion: The current study suggested that TNFα gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNFα.

Melatonin versus chloral hydrate on sleep induction for recording electroencephalography in children: a randomized clinical trial.

Background: Electroencephalography (EEG) plays an essential role in the diagnosis of seizures. EEG recording in children is done with partial sleep deprivation and sedative drugs. To compare the effectiveness of melatonin and chloral hydrate on sleep induction and EEG recording in children. Materials and methods: In a parallel blinded randomized clinical trial study, 78 patients (6 months-5 years) were included to record EEG. Patients were randomly divided into two groups to receive melatonin (0.4 mg/kg) or chloral hydrate (0.5 ml/kg). After receiving the sedative drug, the start and duration of sedation, recovery time, side effects, and epileptiform waves in the EEG were recorded. The data was analyzed using SPSS version 16, and the significance level was determined to be less than 0.05. Results: A total of 78 children, including 34 girls (43.6%) and 44 boys (56.4%) (average age of 27.15±17.15 months), were examined. Success in the induction of sedation was reported by melatonin in 36 patients (92%) and chloral hydrate in 37 patients (95%), which was similar between the two drugs (P=0.5). The start time (P=0.134) and the duration of sedation (P=0.408) were alike between the two drugs. However, compared to the chloral hydrate, the recovery time in the melatonin group was significantly shorter (P<0.001). Side effects were not seen in melatonin, while six children (15%) using chloral hydrate had mild side effects (P=0.013). Epileptiform waves in EEGs were reported to be similar and positive for melatonin in 18 children (50%) and chloral hydrate in 16 children (43%) (P=0.410). Conclusion: The findings show that using melatonin in the dose prescribed in this study had similar effects to success in inducing sedation with the minimum quantity of chloral hydrate. Regardless of the start time and duration of sedation, the shorter recovery time and the absence of side effects are the advantages of using melatonin.

Effect of vitamin D supplementation on inflammatory markers and total antioxidant capacity in breast cancer women using a machine learning technique.

Aim: This study aimed to establish a learning system using an artificial neural network (ANN) to predict the effects of vitamin D supplementation on the serum levels of vitamin D, inflammatory factors, and total antioxidant capacity (TAC) in women with breast cancer. Methods: The data set of the current project was created from women with breast cancer who were referred to the Shafa State Hospital of Patients with Cancers in Ahvaz city, Iran. Modeling was implemented using the data set at the serum levels of vitamin D, tumor necrosis factor-α (TNF-α), transforming growth factor ß (TGF-ß), and TAC, before and after vitamin D3 supplement therapy. A prediction ANN model was designed to detect the effects of vitamin D3 supplementation on the serum level changes of vitamin D, inflammatory factors and TAC. Results: The results showed that the ANN model could predict the effect of vitamin D3 supplementation on the serum level changes of vitamin D, TNF-α, TGF-ß1, and TAC with an accuracy average of 85%, 40%, 89.5%, and 88.1%, respectively. Conclusions: According to the findings of the study, the ANN method could accurately predict the effect of vitamin D3 supplementation on the serum levels of vitamin D, TNF-α, TGF-ß1, and TAC. The results showed that the proposed ANN method can help specialists to improve the treatment process more confidently in terms of time and accuracy of predicting the influence of vitamin D supplementation on the factors affecting the progression of breast cancer (https://www.irct.ir/ identifier: IRCT2015090623924N1).

Association between oral contraceptives with lipid profile: results from Hoveyzeh cohort study (HCS).

BACKGROUND: Oral contraceptives (OCs) affect lipid metabolism, which can cause hyperlipidemia, a risk factor for cardiovascular diseases. The study was designed to evaluate the possible changes in lipid profile due to using OCs. METHODS: A cross-sectional study was conducted from April 2016 to August 2018 among women from the baseline phase Hoveyzeh cohort study (HCS). Sociodemographic data, anthropometric measurements, physical activity, and biochemical blood tests were measured for every participant. Multiple logistic regression was used to adjust the potential confounders. RESULTS: Among 2272 participants, 1549 women were OC users, and 723 women were non-user OCs. The mean lipid profile levels were higher in OC users than in non-user OCs. Odds of abnormal Total cholesterol (TC) in OC users were significantly higher than those of non-users OCs [OR = 1.29 (95% CI;1.05 to 1.58)]. Also, the Odds of abnormal low-density lipoprotein (LDL) in OC users was 12% higher than in non-user OCs. However, no significant relationship between abnormal LDL with Oral Contraceptive Pills (OCPs) was observed. CONCLUSIONS: The mean lipid profile was higher in OC users compared to non-user OCs. This finding highlights the need for public health strategies to prevent and detect hyperlipidemia in user OCs.

The Effect of Memantine Versus Folic Acid on Cognitive Impairment in Patients with Schizophrenia: A Randomized Clinical Trial.

Objective: Schizophrenia, as one of the most severe psychiatric diseases, has a chronic and debilitating process. The majority of patients with schizophrenia do not respond adequately to treatment with common antipsychotic drugs. Therapeutic problems induced by drug side effects as well as undesired results are major challenging issues regarding this disease. This study aimed at evaluating the effect of memantine supplementation on the improvement of cognitive symptoms in patients with schizophrenia. Method : The present clinical trial was performed on 50 patients with acute schizophrenia who were admitted to Kargarnejad Psychiatric Hospital in Kashan in 2022 and who were diagnosed as schizophrenia cases at least three months ago. Patients were randomly divided into either the intervention group (n = 25) or the placebo group (n = 25). The intervention group received 5 mg of memantine per day for three months. The dose of memantine in this group was increased to the maximum of 20 mg per day. The placebo group received 1 mg of folic acid per day for three months. Moreover, an identical routine schizophrenia therapeutic regimen was administered to all patients. The effectiveness of memantine was evaluated using the Wechsler Adult Intelligence Scale (WAIS-III), which assessed cognitive ability in older adults over a 12-week follow-up period. Results: The WAIS-III score in the 12th week of the study was significantly different between the placebo and intervention groups (P = 0.004), such that the score of the memantine group was higher than that of the placebo group. No significant difference was observed between the two groups in terms of drug side effects. Conclusion: Memantine can be supplemented in the treatment of schizophrenia so as to improve the cognitive symptoms of this disorder. However, subsequent studies involving larger sample sizes and different doses seem to be necessary to provide more accurate results in this respect.

The effects of rutin supplement on blood pressure markers, some serum antioxidant enzymes, and quality of life in patients with type 2 diabetes mellitus compared with placebo.

Background: This trial aimed to investigate the effects of rutin supplement in type 2 diabetes mellitus (T2DM) patients. Methods: In this trial with a double-blind and controlled design, fifty patients were randomly divided into intervention (n = 25) and control groups (n = 25) and were treated with 1 g of rutin or placebo for three months, respectively. At the baseline and end of the intervention, mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), systolic and diastolic blood pressure (SBP and DBP), serum levels of antioxidant enzymes, such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) and quality of life (QOL) parameters, were evaluated. Results: Rutin consumption caused a significant reduction in SBP, DBP, PP, MAP, and HR, with a significant increase in SOD, CAT, and GPx and some QOL parameters (emotional limitations, energy and freshness, mental health, social performance, and general health) compared with baseline (p for all <0.05). Also, the mean changes of emotional limitations, energy and freshness, mental health, and general health (unadjusted p for all <0.05) and GPX and SOD (adjusted p for all <0.05) were significantly higher in the rutin group compared with the placebo group. Although, in the supplement group compared with the placebo group, the mean changes of SBP, DBP, MAP, PP, and HR were significantly lower (adjusted p for all <0.05). Conclusion: Rutin consumption improved blood pressure, the levels of antioxidant enzymes, and QOL in patients with T2DM.

High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Obesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet. METHODS: This triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit. DISCUSSION: New evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20190303042905N2 . Registered on 31 January 2021.

An Investigation on Cognitive and Behavioral Effects of Donepezil on Autistic Children in Winter 2020 in Gorgan's Taleghani Pediatric Hospital.

Objectives: The present investigation has been done to study the behavioral effects of donepezil in autistic children, given that not much research has been carried out concerning using this drug for treating autism. Materials & Methods: A cross-sectional and analytic-descriptive study was done on twenty patients with autism, aged 4-17, who visited the neurology clinic of Gorgan's Taleghani Pediatric Hospital and Yasha Pediatric Autism Clinic, Iran from 2019 to 2020. Demographic information, including sex, age, father's education, mother's education ,patient's education, family status, other problems, and ethnicity, were documented using a checklist, having been filled in during interviews with the parents. Before the trial, ABC cognitive and behavioral tests were taken to determine the children's current status. After the tests, these children received a daily dose of donepezil (10mg) before sleep for three months. At the end of the three months, the cognitive and behavioral tests were taken from the children once again. In order to analyze the effects of different factors on the studied variables, including irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech before and after the administration of donepezil in patients, a generalized linear model and to test the effects of donepezil on the studied variables, paired t-test was used. Results: In this study, twenty patients were registered for the investigation, 12 (60%) male and eight (40%) female. Age groups 5-6 had the highest frequency, and age group 17 had the lowest. Regardingthe parents' education, the highest frequency was for bachelor's degrees, and the lowest was for less-than-high school education and master's degree. The highest frequency for the patients' education was kindergarten (60%), and then groups without education (20%) and elementary school-level education (15%). Most of the studied patients (80%) did not have other problems besides autism, and only 20% had other problems besides autism. The family status of 15% of the families was 'separated,' and ethnically, most patients (80%) were Fars, while the rest (20%) were Turkmen. None of the analyzed factors (age, sex, father's education, mother's education, patient's education, other problems, family status, and ethnicity) had a significant effect on the studied variables after the administration of donepezil. Among the studied variables prior to the administration of donepezil and among the analyzed factors, the father's education, the patient's education, other problems, and family status had only a significant effect on stereotypic behavior. The present research findings of the present research indicated that all the studied variables, including irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech, were significantly decreased toward the desired goal. The decreased amounts in irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech after the administration of donepezil were, respectively, 38%, 44%, 54%, 41%, and 54% and on average, these behaviors were reduced by 46%. Conclusion: The present investigation has shown that all the studied variables, including irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech, were significantly decreased towards the desired goal by 46%. This significant decrease is indicative of the effectiveness of the treatment of autism patients with donepezil, and therefore, this drug can be placed as a prominent and essential part of the medical therapy of autism.