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.

Neural stem cell therapies for spinal cord injury repair: an update on recent preclinical and clinical advances.

Traumatic spinal cord injury (SCI) is a leading cause of lifelong disabilities. Permanent sensory, motor and autonomic impairments after SCI are substantially attributed to degeneration of spinal cord neurons and axons, and disintegration of neural network. To date, minimal regenerative treatments are available for SCI with an unmet need for new therapies to reconstruct the damaged spinal cord neuron-glia network and restore connectivity with the supraspinal pathways. Multipotent neural precursor cells (NPCs) have a unique capacity to generate neurons, oligodendrocytes and astrocytes. Due to this capacity, NPCs have been an attractive cell source for cellular therapies for SCI. Transplantation of NPCs has been extensively tested in preclinical models of SCI in the past two decades. These studies have identified opportunities and challenges associated with NPC therapies. While NPCs have the potential to promote neuroregeneration through various mechanisms, their low long-term survival and integration within the host injured spinal cord limit the functional benefits of NPC-based therapies for SCI. To address this challenge, combinatorial strategies have been developed to optimize the outcomes of NPC therapies by enriching SCI microenvironment through biomaterials, genetic and pharmacological therapies. In this review, we will provide an in-depth discussion on recent advances in preclinical NPC-based therapies for SCI. We will discuss modes of actions and mechanism by which engrafted NPCs contribute to the repair process and functional recovery. We will also provide an update on current clinical trials and new technologies that have facilitated preparation of medical-grade human NPCs suitable for transplantation in clinical studies.

Kaempferol alleviates bisphenol A reproductive toxicity in rats in a dose-dependent manner.

BACKGROUND: Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are a major cause of male infertility by disrupting spermatogenesis. OBJECTIVE: Here, we examined the potential protective benefits of kaempferol (KMF), a flavonol known for its antioxidant properties, on BPA-induced reproductive toxicity in adult male rats. METHODS: Human skin fibroblast cells (HNFF-P18) underwent cell viability assays. Thirty-five male Wistar rats were assigned to four groups: 1) control, 2) BPA (10 mg/kg), 3,4) BPA, and different dosages of KMF (1 and 10 mg/kg). The study examined the rats' testosterone serum level, antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), oxidative markers malondialdehyde (MDA) and total antioxidant capacity (TAC), body weight, weight ratios of testis and prostate, and histopathological examinations. RESULTS: The study revealed that using KMF to treat rats exposed to BPA increased cell viability. Moreover, the rats' testosterone levels, which BPA reduced, showed a significant increase after KMF was included in the treatment regimen. Treatment with BPA led to oxidative stress and tissue damage, but simultaneous treatment with KMF restored the damaged tissue to its normal state. Histopathology studies on testis and prostate tissues showed that KMF had an ameliorative impact on BPA-induced tissue damage. CONCLUSIONS: The research suggests that KMF, a flavonol, could protect male rats from the harmful effects of BPA on reproductive health, highlighting its potential healing properties.

Molecular characterization and epidemiological investigation of colistin resistance in carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Tehran, Iran.

BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CRKP) presents a significant challenge to antimicrobial therapy, especially when compounded by resistance to colistin. The objective of this study was to explore molecular epidemiological insights into strains of clinical K. pneumoniae that produce carbapenemases and exhibit resistance to colistin. Eighty clinical isolates of CRKP were obtained from Milad Hospital in Tehran, Iran. Antimicrobial susceptibility and colistin broth disk elution were determined. PCR assays were conducted to examine the prevalence of resistance-associated genes, including blaKPC, blaIMP, blaVIM, blaOXA-48, blaNDM and mcr-1 to -10. Molecular typing (PFGE) was used to assess their spread. RESULTS: Colistin resistance was observed in 27 isolates (33.7%) using the Broth Disk Elution method. Among positive isolates for carbapenemase genes, the most frequent gene was blaOXA-48, identified in 36 strains (45%). The mcr-1 gene was detected in 3.7% of the obtained isolates, with none of the other of the other mcr genes detected in the studied isolates. CONCLUSION: To stop the spread of resistant K. pneumoniae and prevent the evolution of mcr genes, it is imperative to enhance surveillance, adhere rigorously to infection prevention protocols, and implement antibiotic stewardship practices.

Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.

Individuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms. This study aimed to comparatively investigate the relationship between lncRNAs (eosinophil granule ontogeny transcript (EGOT), negative regulator of antiviral response (NRAV), and negative regulator of interferon response (NRIR)), alongside interferon-stimulated genes (ISGs) like ISG-15 and interferon-induced transmembrane protein 3 (IFITM3) in COVID-19 patients with asymptomatic, moderate, and severe symptoms. Buffy coat samples were collected from 17 asymptomatic, 23 moderate, 22 severe patients, and 44 healthy controls. Quantitative real-time PCR was utilized to determine the expression levels. In a comparison between COVID-19 patients and healthy individuals, higher expression levels of EGOT and NRAV were observed in severe and moderate patients. NRIR expression was increased across all patient groups. Meanwhile, ISG15 expression decreased in all patient groups, and the moderate group showed a significant decrease in IFITM3 expression. Comparing COVID-19 patient groups, EGOT expression was significantly higher in moderate COVID-19 patients compared to asymptomatic patients. NRAV was higher in moderate and severe patients compared to asymptomatic. NRIR levels did not differ significantly between the COVID-19 patient groups. ISG15 was higher in moderate and severe patients compared to asymptomatic. IFITM3 expression was significantly higher in severe patients compared to the moderate group. In severe COVID-19 patients, EGOT expression was positively correlated with NRAV levels. EGOT and NRAV showed a significant positive correlation in asymptomatic patients, and both were positively correlated with IFITM3 expression. This study suggests that EGOT, NRAV, NRIR, ISG15, and IFITM3 may serve as diagnostic biomarkers for COVID-19. The lncRNA NRAV may be a good biomarker in a prognostic panel between asymptomatic and severe patients in combination with other high-sensitivity biomarkers. EGOT, NRAV, and ISG15 could also be considered as specific biomarkers in a prognostic panel comparing asymptomatic and moderate patients with other high-sensitivity biomarkers.

Microstates of Accelerating and Supersymmetric AdS_{4} Black Holes from the Spindle Index.

We provide a first principles derivation of the microscopic entropy of a very general class of supersymmetric, rotating, and accelerating black holes in AdS_{4}. This is achieved by analyzing the large-N limit of the spindle index and completes the construction of the first example of a holographic duality involving supersymmetric field theories defined on orbifolds with conical singularities.

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).

Liver injury in COVID-19: an insight into pathobiology and roles of risk factors.

COVID-19 is a complex disease that can lead to fatal respiratory failure with extrapulmonary complications, either as a direct result of viral invasion in multiple organs or secondary to oxygen supply shortage. Liver is susceptible to many viral pathogens, and due to its versatile functions in the body, it is of great interest to determine how hepatocytes may interact with SARS-CoV-2 in COVID-19 patients. Liver injury is a major cause of death, and SARS-CoV-2 is suspected to contribute significantly to hepatopathy. Owing to the lack of knowledge in this field, further research is required to address these ambiguities. Therefore, we aimed to provide a comprehensive insight into host-virus interactions, underlying mechanisms, and associated risk factors by collecting results from epidemiological analyses and relevant laboratory experiments. Backed by an avalanche of recent studies, our findings support that liver injury is a sequela of severe COVID-19, and certain pre-existing liver conditions can also intensify the morbidity of SARS-CoV-2 infection in synergy. Notably, age, sex, lifestyle, dietary habits, coinfection, and particular drug regimens play a decisive role in the final outcome and prognosis as well. Taken together, our goal was to unravel these complexities concerning the development of novel diagnostic, prophylactic, and therapeutic approaches with a focus on prioritizing high-risk groups.

Exploiting Apical Sodium-Dependent Bile Acid Transporter (ASBT)-Mediated Endocytosis with Multi-Functional Deoxycholic Acid Grafted Alginate Amide Nanoparticles as an Oral Insulin Delivery System.

OBJECTIVE: Oral administration of insulin is a potential candidate for managing diabetes. However, it is obstructed by the gastrointestinal tract barriers resulting in negligible oral bioavailability. METHODS: This investigation presents a novel nanocarrier platform designed to address these challenges. In this regard, the process involved amination of sodium alginate by ethylene diamine, followed by its conjugation with deoxycholic acid. RESULTS: The resulting DCA@Alg@INS nanocarrier revealed a significantly high insulin loading content of 63.6 ± 1.03% and encapsulation efficiency of 87.6 ± 3.84%, with a particle size of 206 nm and zeta potentials of -3 mV. In vitro studies showed sustained and pH-dependent release profiles of insulin from nanoparticles. In vitro cellular studies, confocal laser scanning microscopy and flow cytometry analysis confirmed the successful attachment and internalization of DCA@Alg@INS nanoparticles in Caco-2 cells. Furthermore, the DCA@Alg@INS demonstrated a superior capacity for cellular uptake and permeability coefficient relative to the insulin solution, exhibiting sixfold and 4.94-fold enhancement, respectively. According to the uptake mechanism studies, the results indicated that DCA@Alg@INS was mostly transported through an energy-dependent active pathway since the uptake of DCA@Alg@INS by cells was significantly reduced in the presence of NaN3 by ~ 92% and at a low temperature of 4°C by ~ 94%. CONCLUSIONS: Given the significance of administering insulin through oral route, deoxycholic acid-modified alginate nanoparticles present a viable option to surmount various obstacles presented by the gastrointestinal.

The role of specialized pro-resolving mediators (SPMs) in inflammatory arthritis: A therapeutic strategy.

Rheumatoid arthritis (RA) is classified as a persistent inflammatory autoimmune disorder leading to the subsequent erosion of articular cartilage and bone tissue originating from the synovium. The fundamental objective of therapeutic interventions in RA has been the suppression of inflammation. Nevertheless, conventional medicines that lack target specificity may exhibit unpredictable effects on cell metabolism. In recent times, there has been evidence suggesting that specialized pro-resolving mediators (SPMs), which are lipid metabolites, have a role in facilitating the resolution of inflammation and the reestablishment of tissue homeostasis. SPMs are synthesized by immune cells through the enzymatic conversion of omega-3 fatty acids. In the context of RA, there is a possibility of dysregulation in the production of these SPMs. In this review, we delve into the present comprehension of the endogenous functions of SPMs in RA as lipids that exhibit pro-resolutive, protective, and immunoresolvent properties.

The association between healthy eating index-2015 with anthropometric, cardiometabolic and hepatic indices among patients with non-alcoholic fatty liver disease.

BACKGROUND: Obesity, cardiovascular diseases, and metabolic disorders are common problems among participants with non-alcoholic fatty liver disease (NAFLD). However, the association between these problems and the healthy eating index-2015 (HEI-2015) remains unknown. Although the HEI-2015 originated from American dietary guidelines, its comprehensive evaluation of diet quality provides valuable insights for various populations, including Iranians. Therefore, the objective of this study was to investigate the association between anthropometric, hepatic, and cardio-metabolic indices with HEI-2015 scores in participants with NAFLD. METHODS: We conducted a cross-sectional analysis of data from the Hoveyzeh Cohort Study, which included adults aged 35 to 70 years between 2016 and 2018. A total of 664 participant with NAFLD (452 females and 212 males) were included in the analysis. The HEI-2015 was assessed using the Food Frequency Questionnaire (FFQ). Various indices, including the body shape index (ABSI), atherogenic index of plasma (AIP), visceral adiposity index (VAI), lipid accumulation product (LAP), cardiometabolic index (CMI), lipoprotein combine index (LCI), AST/ALT ratio, ALD/NAFLD index, and hepatic steatosis index (HSI), were calculated. RESULTS: No significant differences were observed in anthropometric, cardio-metabolic, and hepatic indices across the quartiles of HEI-2015. However, among participants with NAFLD, men had significantly higher AIP and LCI levels, while women had significantly higher BMI, ABSI, VAI, LAP, and CMI levels. Additionally, women with NAFLD exhibited higher AST/ALT and HSI levels but lower ALD/NAFLD levels compared to men with NAFLD. Linear regression analysis among men with NAFLD revealed a significant negative correlation between HEI-2015 score and HSI in both the unadjusted model (ß=-0.131, SE = 0.058, p = 0.024) and the adjusted model for energy intake (ß=-0.129, SE = 0.058, p = 0.028). CONCLUSION: The present study demonstrated a correlation between lower HEI-2015 scores and an increased risk of steatosis in men with NAFLD. Moreover, our findings highlighted gender-related differences in NAFLD and cardio-metabolic disorders.

Historical roots of the stigma of epilepsy: A review of the classic Iranian literature.

BACKGROUND: The stigma toward epilepsy is a daily challenge for people with epilepsy (PWE) and can influence the well-being and prognosis of these individuals. However, the cultural origins of such stigma have sparsely been examined. In this study, we aimed to investigate the classic Persian literature to gain insight into the historical and cultural beliefs and opinions regarding epilepsy as a determinant in developing stigma towards PWE. METHODS: In this narrative review of the classic Persian literature, we investigated the opinions and beliefs regarding epilepsy and PWE. In February 2023, we searched https://ganjoor.net (an open-access database of Iranian literature) for the relevant literary materials (poem and prose) using the Persian translation of the terms epilepsy (Sar'e) and epileptic (Masroo'e). Two clinical researchers went through the results and extracted the related materials under the supervision of two experts in Persian literature. A bilingual academic translated the included literary materials from Persian to English. RESULTS: Our search yielded 57 literature materials by 31 poets and writers from the 4th to 14th Hijri centuries, roughly coinciding with the past Gregorian millennium (1000-2000 AC). We classified the literary concepts related to epilepsy stigma into five subgroups: (i) a simile for pain and suffering; (ii) an atonement for blasphemous beliefs or a disease caused by supernatural power; (iii) a sign of madness, insanity, and lack of wisdom; (iv) a celestial observation; and (v) a subject for jokes. CONCLUSIONS: Classic Persian literature considered epilepsy as a simile for suffering and a sign of insanity that is caused by blasphemous beliefs or celestial objects, with PWE classified as insane and unwise. While such depictions became less prevalent after the 14th century CE, they can give rise to misconceptions and negative stigma toward PWE and should be addressed in modern culture. Each society should critically investigate its socio-cultural origins of stigma and rectify such misbeliefs.

Assessment of the appropriate cutoff points for anthropometric indices and their relationship with cardio-metabolic indices to predict the risk of metabolic associated fatty liver disease.

BACKGROUND: Research on Metabolic Associated Fatty Liver Disease (MAFLD) is still in its early stages, with few studies available to identify and predict effective indicators of this disease. On the other hand, early diagnosis and intervention are crucial to reduce the burden of MAFLD. Therefore, the aim of this research was to investigate the effectiveness of eleven anthropometric indices and their appropriate cut-off values as a non-invasive method to predict and diagnose MAFLD in the Iranian population. METHODS: In this cross-sectional study, we analyzed baseline data from the Hoveyzeh Cohort Study, a prospective population-based study conducted in Iran that enrolled a total of 7836 subjects aged 35 to 70 years from May 2016 through August 2018. RESULTS: The optimal cut-off values of anthropometric indices for predicting MAFLD risk were determined for waist circumference(WC) (102.25 cm for males and 101.45 cm for females), body mass index (BMI) (27.80 kg/m2 for males and 28.75 kg/m2 for females), waist-to-hip ratio (WHR) (0.96 for both males and females), waist-to-height ratio (WHtR) (0.56 for males and 0.63 for females), body adiposity index (BAI) (23.24 for males and 32.97 for females), visceral adiposity index (VAI) (1.64 for males and 1.88 for females), weight-adjusted waist index (WWI) (10.63 for males and 11.71 for females), conicity index (CI) (1.29 for males and 1.36 for females), body roundness index (BRI) (4.52 for males and 6.45 for females), relative fat mass (RFM) (28.18 for males and 44.91 for females) and abdominal volume index (AVI) (18.85 for males and for 21.37 females). VAI in males (sensitivity: 77%, specificity: 60%, Youden's Index: 0.37) and RFM in females (sensitivity: 76%, specificity: 59%, Youden's Index: 0.35) were found to have higher sensitivity and specificity compared to other anthropometric indices. Furthermore, anthropometric indices demonstrated statistically significant correlations with various hepatic and cardiometabolic indices. Among these, the strongest positive correlations were observed between WC, BMI, BAI, BRI, and AVI with the Hepatic Steatosis Index (HSI), TyG-BMI, and TyG-WC, as well as between VAI and the Atherogenic Index of Plasma (AIP), Lipid Accumulation Product (LAP), Cardiometabolic Index (CMI), and the Triglyceride and Glucose (TyG) Index. CONCLUSION: Anthropometric indices are effective in predicting MAFLD risk among Iranian adults, with WWI, VAI, and RFM identified as the strongest predictors. The proposed cutoff values could serve as a straightforward and non-invasive methods for the early diagnosis of MAFLD.

The association between dietary inflammatory index with some cardio-metabolic risk indices among the patients with type 2 diabetes from Hoveyzeh cohort study: a cross-sectional study.

BACKGROUND: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. METHODS: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. RESULTS: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). CONCLUSION: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications.

Evaluation of blood pressure variation in recovered COVID-19 patients at one-year follow-up: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has various sequelae, one of which might be hypertension. We aimed to evaluate COVID-19's impact on blood pressure (BP) in non-hospitalized patients at one-year follow-up. METHOD: A total of 7,950 consecutive COVID-19 patients regularly visiting our cardiology clinic were retrospectively screened. Patients' electronic medical records including demographics, comorbidities, vital signs, treatments, and outcomes, were reviewed by two physicians. Individuals with at least one BP measurement in the three months preceding COVID-19 and one measurement in 12 months or more following recovery were included. BP levels before and after COVID-19 were compared using the paired t-test. RESULTS: 5,355 confirmed COVID-19 patients (mean age 55.51 ± 15.38 years) were included. Hypertension (56.9%) and diabetes mellitus (34%) were the predominant comorbidities, and 44.3% had prior major adverse cardiovascular events. Both systolic (126.90 ± 20.91 vs. 139.99 ± 23.94 mmHg, P < 0.001) and diastolic BP (80.54 ± 13.94 vs. 86.49 ± 14.40 mmHg, P < 0.001) were significantly higher post-COVID-19 vs. pre-COVID-19. Notably, 456 (14%) hypertensive patients experienced exacerbated hypertension, while 408 (17%) patients developed new-onset hypertension, overall 864 (16%) of patients had exacerbation or new hypertension. Linear regression analysis revealed that advanced age, smoking, previous cardiovascular events, hypertension, and diabetes mellitus predict increased BP following COVID-19 (P < 0.001). CONCLUSION: COVID-19 raised systolic and diastolic BP in the long term in non-hospitalized patients, with over one-sixth developing new-onset or exacerbated hypertension. All patients should be evaluated regarding BP, following COVID-19 recovery, particularly those with the mentioned predictive factors. (clinicaltrial.gov: NCT05798208).

X marks the spot: Accurate energies from intersecting extrapolations of continuum quantum Monte Carlo data.

We explore the application of an extrapolative method that yields very accurate total and relative energies from variational and diffusion quantum Monte Carlo (VMC and DMC) results. For a trial wave function consisting of a small configuration interaction (CI) wave function obtained from full CI quantum Monte Carlo and reoptimized in the presence of a Jastrow factor and an optional backflow transformation, we find that the VMC and DMC energies are smooth functions of the sum of the squared coefficients of the initial CI wave function and that quadratic extrapolations of the non-backflow VMC and backflow DMC energies intersect within uncertainty of the exact total energy. With adequate statistical treatment of quasi-random fluctuations, the extrapolate and intersect with polynomials of order two method is shown to yield results in agreement with benchmark-quality total and relative energies for the C2, N2, CO2, and H2O molecules, as well as for the C2 molecule in its first electronic singlet excited state, using only small CI expansion sizes.

Mini review: human clinical studies of stem cell therapy in keratoconus.

Treatment of keratoconus is one of the most interesting research fields for researchers in the world. Regenerative medicine based on human stem cells in the treatment of keratoconus has recently received attention. Despite extensive laboratory and animal studies in regenerative medicine of cornea, there are limited clinical studies in keratoconus. These studies showed promising results of stem cell therapy. In initial studies, the transplantation of these cells into stroma was associated with increased vision and improved corneal parameters without side effects. In this article, we tried to review different aspects of keratoconus stem cell therapy, including cell extraction and culture, surgical procedure, effectiveness and safety of this method in human clinical studies.

Molecular typing of a collection of Iranian clinical Trichophyton tonsurans isolates based on the non-transcribed spacer region of rDNA and antifungal susceptibility testing of the species.

INTRODUCTION: Wrestling, considered the national sport of Iran, has gained immense popularity among Iranians. Wrestlers frequently encounter skin conditions, with dermatophyte fungal infections, particularly tinea gladiatorum (TG), being a common issue. TG, caused by the Trichophyton genus, has emerged as a major health concern for wrestlers and other contact sport athletes worldwide. This study aimed to assess the genotypic diversity and antifungal susceptibility of Trichophyton tonsurans isolates responsible for TG in Iranian wrestlers from Mazandaran province, northern Iran. MATERIALS AND METHODS: A total of 60 clinical T. tonsurans isolates collected from various cities in Mazandaran, were included in the study. The isolates were identified through PCR-restriction fragment length polymorphism and sequencing methods. Genomic DNA was extracted from these isolates, and the non-transcribed spacer (NTS) region of ribosomal RNA (rRNA) was targeted for genotyping using newly designed primers. Haplotype analysis was performed to explore genetic diversity, and antifungal susceptibility to terbinafine (TRB) and itraconazole (ITC) was assessed. RESULTS: The results revealed five distinct NTS types: NTS-I, NTS-II, NTS-III, NTS-IV and NTS-V, with NTS-IV being the most prevalent. The distribution of NTS types varied across different cities, suggesting potential transmission patterns among wrestlers. Antifungal susceptibility testing showed that all isolates were susceptible to TRB, while one isolate demonstrated resistance to ITC. Genotypic diversity was not correlated with antifungal susceptibility, emphasising the importance of monitoring susceptibility to ensure effective treatment. Haplotype analysis highlighted significant genetic diversity among the T. tonsurans isolates. This diversity may be attributed to factors such as human-to-human transmission, geographic location and lifestyle changes. The study's findings underscore the need for comprehensive genotypic analysis to understand the epidemiology and evolution of T. tonsurans infections in athletes. CONCLUSION: In conclusion, this study provides valuable insights into the genotypic diversity and antifungal susceptibility of T. tonsurans isolates causing TG in Iranian wrestlers. The presence of multiple NTS types and varying susceptibility patterns highlights the complexity of T. tonsurans infections in this population. Further research is warranted to track the transmission routes and genetic evolution of T. tonsurans strains among wrestlers and develop effective control measures.

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.

The effect of soy isoflavones supplementation on metabolic status in patients with non-alcoholic fatty liver disease: a randomized placebo controlled clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) accounts as a crucial health concern with a huge burden on health and economic systems. The aim of this study is to evaluate the effect of soy isoflavones supplementation on metabolic status in patients with NAFLD. METHODS: In this randomized clinical trial, 50 patients with NAFLD were randomly allocated to either soy isoflavone or placebo groups for 12 weeks. The soy isoflavone group took 100 mg/d soy isoflavone and the placebo group took the similar tablets containing starch. Anthropometric indices, blood lipids, glycemic parameters and blood pressure were measured at the beginning and at the end of the study. RESULTS: At the end of week 12 the level of serum triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TC) was significantly decreased only in soy isoflavone group compared to baseline (P < 0.05). Although waist circumference (WC) decreased significantly in both groups after 12 weeks of intervention (P < 0.05), hip circumference (HC) decreased significantly only in soy isoflavone group (P = 0.001). No significant changes observed regarding high density lipoprotein (HDL) and blood pressure in both groups. At the end of the study, serum glucose level was significantly decreased in the placebo group compared to baseline (P = 0.047). No significant changes demonstrated in the soy isoflavone group in regard to glycemic parameters (P > 0.05). CONCLUSIONS: This study revealed that soy isoflavones could significantly reduce TG, LDL TC, WC and HC in NAFLD patients. TRIAL REGISTRATION: The Ethics committee of Ahvaz Jundishapur University of Medical Sciences approved the protocol of the present clinical research (IR.AJUMS.REC.1401.155). The study was in accordance with the Declaration of Helsinki. This study's registered number and date are IRCT20220801055597N1 and 20.09.2022, respectively at https://fa.irct.ir .