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The present study was conducted to investigate the differences in cadmium (Cd) and mercury (Hg) concentrations between children with autism spectrum disorder (ASD) and controls. In this systematic review and meta-analysis study, three thousand one hundred forty-five studies were collected from scientific databases including Web of Science, Scopus, PubMed, and Google Scholar from January 2000 to October 2022 and were investigated for eligibility. As a result, 37 studies published in the period from 2003 to 2022 met our inclusion criteria and were considered in the meta-analysis. The heterogeneity assumption was evaluated using the Chi-squared-based Q-test and I-squared (I 2 ) statistics. The pooled estimates were shown in the forest plots with Hedges' g (95% confidence interval) values. The random effects model demonstrated that there is no significant difference in the blood (Hedges' g: 0.14, 95% CI: 0.45, 0.72, p  > 0.05), hair (Hedges' g: 0.12, 95% CI: 0.26, 0.50, p  > 0.05), and urinary (Hedges' g: 0.05, 95% CI: 0.86, 0.76, p  > 0.05) Cd levels of the case group versus control subjects. Moreover, the pooled findings of studies showed no significant difference in the blood (Hedges' g: 1.69, 95% CI: 0.09, 3.48, p  > 0.05), hair (Hedges' g: 3.42, 95% CI: 1.96, 8.80, p  > 0.05), and urinary (Hedges' g: 0.49, 95% CI: 1.29 - 0.30, p  > 0.05) Hg concentrations. The results demonstrated no significant differences in Hg and Cd concentrations in different biological samples of children with ASD compared to control subjects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC 50  = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC 50  = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with K i  = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Since launching health health-promoting settings approach to health by WHO, valuable progress has happened in implementing its holistic concepts in settings such as cities, schools, workplaces, hospitals and healthcare services. However, significant knowledge-intention-success gaps still exist in creating sustainable health-promoting changes in settings. The complexity of the task of bridging this gap has contributed to the call for a complexity-informed paradigm shift to health as well as settings, followed by increasing consultation of relevant complexity theories, frameworks and tools in health research. This paper provides a critical scoping review of the application of complex adaptive system (CAS) theory in settings-based health promotion research. We included 14 papers, mostly qualitative studies, reporting on planning or implementation of change initiatives, less on its evaluation. CAS theory application was often incomplete thereby reducing the potential benefit of using this lens to understand change management. We suggest some recommendations how to comprehensively apply the CAS theory in setting-based health research and to report on all CAS characteristics to enhance the understanding of settings as adaptive health-promoting settings., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: TPP1 variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of TPP1 variants is presented in an Iranian cohort and a novel pathogenic variant is described., Methods: This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children's Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing., Results: Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the TPP1 gene was identified., Discussion: The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Background: There is an increasing need for sexual well-being and health promotion strategies that effectively engage men. Researchers have evaluated the efficacy of sexual and reproductive health-related and marital enhancement interventions in male-dominated societies. However, few have focused on culturally appropriate and gender-specific program effects., Objective: This review aims to evaluate evidence of existing interventions aimed at enriching marital relationships and sexual well-being in adult men., Materials and Methods: This scoping review was conducted by searching various databases (CINAHL, PsycINFO, EMBASE, Google Scholar, PubMed, Scopus, SID, and Noormags), and other available resources in both English and Persian languages. We located all publications up to January 2023 with no time restriction. Inclusion criteria were studies targeting men in the enrichment of marital and sexual relationships, which focus on marital/sexual enrichment, sexual and reproductive health (SRH) program, passionate relationship, or sexual satisfaction as the main outcomes. PRISMA guidelines were utilized in this review., Results: Of records 34,405 retrieved by searching, after removing duplicate articles, 8 articles were included based on the inclusion criteria. SRH program was the main focus of 6 articles. Marital and sexual enhancement were common areas of focus in 2 studies. Research methods included 2 semi-experimental, 3 clinical trials, 1 systematic review, 1 content analysis, and a mixed method. According to the assessment result, 4 articles were moderate and 4 were of high quality., Conclusion: Our findings reveal that a small number of interventions specifically offering SRH or marital and sexual enhancement programs to men should be conducted. As the majority were heterosexual couples, we recommend male-focused programs recognizing men's sexuality., Competing Interests: The authors do not mention any conflict of interest in this article., (Copyright © 2023 Abdollahzadeh Sardehaei et al.)

Background: Leishmaniasis is a parasitic disease caused by the Leishmania protozoan affecting millions of people worldwide, especially in tropical and subtropical regions. The immune response involves the activation of various cells to eliminate the infection. Understanding the complex interplay between Leishmania and the host immune system is crucial for developing effective treatments against this disease., Methods: This study collected extensive transcriptomic data from macrophages, dendritic, and NK cells exposed to Leishmania spp. Our objective was to determine the Leishmania-responsive genes in immune system cells by applying meta-analysis and feature selection algorithms, followed by co-expression analysis., Results: As a result of meta-analysis, we discovered 703 differentially expressed genes (DEGs), primarily associated with the immune system and cellular metabolic processes. In addition, we have substantiated the significance of transcription factor families, such as bZIP and C2H2 ZF, in response to Leishmania infection. Furthermore, the feature selection techniques revealed the potential of two genes, namely G0S2 and CXCL8, as biomarkers and therapeutic targets for Leishmania infection. Lastly, our co-expression analysis has unveiled seven hub genes, including PFKFB3, DIAPH1, BSG, BIRC3, GOT2, EIF3H, and ATF3, chiefly related to signaling pathways., Conclusions: These findings provide valuable insights into the molecular mechanisms underlying the response of immune system cells to Leishmania infection and offer novel potential targets for the therapeutic goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rezaei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil-azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC 50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure-activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil-azole hybrids can be considered as potential cytotoxic agents., (© 2023. The Author(s).)

Background: Cinnamic acid, an active compound in cinnamon spp., has anti-inflammatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases., Objectives: Evaluate cinnamic acid's effects on colitis in rats., Methods: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon., Results: Effective reduction of inflammation in acetic acid-induced colitis was achieved through Cinnamic acid administration at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation., Conclusion: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Since the (Covid-19) pandemic outbreak, questioning regarding climate and incident of Covid-19 infection rates has been debated, while there is no clear research evidence until now in Iran. This study has focused on investigating the association between Covid-19 cases and demographic -meteorological factors in arid and semi-arid zones of Iran (from March 1, 2020, to January 31, 2022) by analyzing with Via Poisson and negative binomial regression. As a result, the incidence rate of both Covid-19 hospitalization and mortality cases reached peaks in the summer followed by the autumn. Interestingly, Covid-19 hospitalization cases are associated with humidity, temperature, and wind factors seasonally and monthly, but mortality cases are just associated with wind. In conclusion, the result demonstrated that demographicand meteorological factorsare positively and negatively associated with Covid-19 cases. Therefore, identifying the environmental factors contributing to the excess Covid-19 can help to prevent future pandemic waves in Iranian arid and semi-arid zone.

Oxidative stress plays an important role in the pathology of thyroid disorders. This study examined the effect of gallic acid (GA) on the oxidative status and expression of liver antioxidant genes including thioredoxin (TXN1 & TXN2) and thioredoxin reductase1 (TXNRd1) in hypo- and hyperthyroid rat models. Forty-nine male Wistar rats were randomly assigned into seven groups as follows: control group, hypothyroid and hyperthyroid groups respectively induced by propylthiouracil and levothyroxine, hypo- and hyper thyroid-treated groups (where the groups were separately treated with 50 and 100 mg/kg of GA daily, orally). The levels of thyroid hormones and serum oxidative stress markers were evaluated after 5 weeks. The relative expression of TXN1,2 and TXNRd1 genes was measured via real-time qRT-PCR. The mean level of total antioxidant capacity (TAC), malondialdehyde, and uric acid index diminished in the hypothyroid group. Increased TAC reached almost the level of control in hypothyroid groups treated with GA. Elevation of thiol index in the hypothyroid group was observed ( p  < 0.01), which diminished to the control level after GA treatment. The relative expression of TXN1, TXNRd1, and TXN2 genes in the hypothyroid and hyperthyroid groups significantly increased compared to the control group ( p  ≥ 0.05), but in the groups treated with GA, the expression of these genes declined significantly ( p  ≥ 0.05). Our results indicated GA can affect the expression of TXN system genes in the rat liver. Also, the results suggest GA has a more positive effect on modulating serum oxidative parameters in hypothyroid rat models than in hyperthyroid.

Introduction: Successful frozen-thawed embryo transfer (FTET) depends on multiple factors among which the woman's vaginal microbiota has recently been considered important. Using probiotic products, such as Lactovag in infertile women, the vaginal microbiome can become close to the healthy status., Objectives: The aim of this study was to evaluate the effect of Lactovag on normalizing vaginal microbiome, as well as its role in improving pregnancy outcomes in FTET cycles., Patients and Methods: This randomized blinded clinical trial was conducted on 103 patients undergoing Assisted Reproductive Technology (ART) treatment at a tertiary university-based hospital between January and August of 2019. In the experiment group, the vaginal suppository Lactavag was prescribed, whereas in the control group, patients did not receive any microbiome supplements. Then, the pregnancy rate was compared in the two groups., Results: There were no significant differences in baseline characteristics between the two study groups (p > 0.05). Positive B hCG was present in 28% (n = 26) of women, clinical pregnancy was achieved in 23.4% (n = 22) of them and fetal heart rate was detected in 21.3% (n = 20). These proportions were higher in the Lactovag group, although these differences were not significant (p > 0.05). Results showed that although transferring fetuses with grade A increased the odds of pregnancy with 1.53 (p = 0.001) folds, this ratio would be improved using Lactovag;1.68 (P value = 0.008)., Conclusions: It seems that the vaginal microbiota critically interplays with women's health and reproduction. A probiotic agent such as Lactovag can be useful in normalizing this environment and improving pregnancy outcomes in infertile women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Essential oils (EOs) are natural products called volatile oils or aromatic and ethereal oils derived from various parts of plants. They possess antioxidant and antimicrobial properties, which offer natural protection against a variety of pathogens and spoilage microorganisms. Studies conducted in the last decade have demonstrated the unique applications of these compounds in the fields of the food industry, agriculture, and skin health. This systematic article provides a summary of recent data pertaining to the effectiveness of EOs and their constituents in combating fungal pathogens through diverse mechanisms. Antifungal investigations involving EOs were conducted on multiple academic platforms, including Google Scholar, Science Direct, Elsevier, Springer, Scopus, and PubMed, spanning from April 2000 to October 2023. Various combinations of keywords, such as "essential oil," "volatile oils," "antifungal," and " Aspergillus species," were used in the search. Numerous essential oils have demonstrated both in vitro and in vivo antifungal activity against different species of Aspergillus , including A. niger , A. flavus , A. parasiticus , A. fumigatus , and A. ochraceus. They have also exhibited efficacy against other fungal species, such as Penicillium species, Cladosporium , and Alternaria. The findings of this study offer novel insights into inhibitory pathways and suggest the potential of essential oils as promising agents with antifungal and anti-mycotoxigenic properties. These properties could make them viable alternatives to conventional preservatives, thereby enhancing the shelf life of various food products., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The food industry has always sought to produce products enriched with vitamins, probiotics, polyphenols, and other bioactive compounds to improve physiological function, enhance nutritional value, and provide health. These compounds are essential for human health, and their deficiency can lead to adverse effects. Therefore, food enrichment is an important strategy to improve the nutritional value and, in some cases, improve the quality of food. Recently, functional foods have been very popular around the world. Among food products, dairy products constitute a major part of people's diet, and due to the high consumption of dairy products, including yogurt, the enrichment of this product effectively reduces or prevents diseases associated with nutritional deficiencies. Most consumers generally accept yogurt due to its high nutritional value and low price. So, it can be considered a good candidate for enrichment with micronutrients and probiotics. In recent years, using functional foods to prevent various diseases has become a popular topic for research. In this study, the effect of fortified yogurt in preventing diseases and improving deficiencies has been investigated, and it has been proven that super healthy yogurt has a positive effect on human health., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

In this study, we aimed to investigate the effect of the co-treatment with apigenin and doxorubicin (DOX) on K562 cells. Our results show that apigenin (0, 40, 60, 80 ,100 µM) and DOX (0-10 µM) as single therapy, could decrease K562 cell viability (after 24 h of treatment) in a dose-dependent manner. Additionally, the co-treatment with apigenin (60, 80 µM) and 10 µM of DOX led to a greater reduction in cell growth (CI: 0.92 and 0.97) after 24 h of treatment compared to the single DOX treatment ( p  < 0.05). Consequently, apigenin and DOX, either as single or as co-treatment (24 h of treatment), were indicated to induce apoptosis in K562 cells through morphological studies, RT-qPCR, and western-blot analysis. Eventually, the expressions of Caspase 3, 6, 7, and 9 genes in the single treatment with DOX had higher alteration compared to the co-treatment with DOX and apigenin ( p  < 0.05).

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recently, miRNAs have been regarded as potential candidates for mediating therapeutic functions by targeting genes related to drug response. In this study, we suggested that plasma miRNAs may be correlated with response to trastuzumab in HER2-positive breast cancer patients. To determine whether miR-195, miR-23b-3p, miR-1246, and miR-34c-3p are involved in trastuzumab resistance, we screened their expressions in the BT-474 cell line, which was followed by plasma analysis from 20 trastuzumab-resistant HER2-positive breast cancer patients and 20 nonresistance subjects. Then, TargetScan, Pictar, and miRDB were applied to find the possible targets of the selected miRNAs. In addition, the expression status of admitted targets was evaluated. Our results showed that in resistant BT-474 cells, miR-1246, and miR-23b-3p were significantly upregulated, and miR-195-5p and miR-34c-3p were downregulated. In plasma analysis, we found miR-195-5p, miR-34c-3p, and miR-1246 meaningfully diminished in the resistant group, while the expression of miR-23b-3p was not statistically different. The expression levels of confirmed targets by qRT-PCR showed that the expression of RAF1, AKT3, c-MET, CCND1, PHLPP2, MYB, MAP2K1, and PTEN was significantly upregulated, while the expression of CCNG2 was significantly downregulated. The networks of miRNAs with their confirmed targets improved comprehension of miRNA-mediated therapeutic responses to trastuzumab and might be proposed for more characterization of miRNA functions. Moreover, these data indicated that miR-195-5p, miR-34c-3p, and miR-1246 could be possible biomarkers for prognosis and early detection of the trastuzumab-resistant group from the sensitive group of HER2-positive breast cancer patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Metabolic by-products are part of the so-called postbiotics of probiotics and other beneficial microorganisms, particularly lactic acid bacteria, which have gained popularity as a feasible alternative to improving food quality and safety. Postbiotics in dry and liquid forms can be easily integrated into food formulations and packaging materials, exhibiting antimicrobial and antioxidant effects owing to the presence of multiple antimicrobials, such as organic acids, bacteriocins, exopolysaccharides and bioactive peptides. Postbiotics can thus control the growth of pathogens and spoilage microorganisms, thereby extending the shelf life of food products. Because of their ability to be easily manufactured without requiring extensive processing, postbiotics are regarded as a safer and more sustainable alternative to synthetic preservatives, which can have negative environmental consequences. Additionally, food manufacturers can readily adopt postbiotics in food formulations without significant modifications. This systematic review provides an in-depth analysis of studies on the use of postbiotics in the biopreservation and packaging of a wide range of food products. The review evaluates and discusses the types of microorganisms, postbiotics preparation and modification techniques, methods of usage in dairy products, meat, poultry, seafood, fruits, vegetables, bread, and egg, and their effects on food quality and safety.

Background: Nurses working in neonatal intensive care units play a crucial role in providing care to critically ill or premature neonates. However, is not without its challenges, particularly when it comes to making difficult ethical decisions about end-of-life care. In some cases, neonates do not survive despite the best efforts of medical professionals. The present study aimed to investigate the relationship between moral distress, ethical climate, and attitudes towards end-of-life care among nurses working in neonatal intensive care units., Methods: This is a descriptive-analytical cross-sectional study (May 21, 2021).The research population included 126 nurses working in neonatal intensive care units in Kerman province (Kerman, Jiroft, Bam, and Rafsanjan). Data collection tools included four questionnaires: demographic information, the Frommelt Attitudes towards Care of the Dying (FATCOD), the Hospital Ethical Climate Survey, and the Moral Distress Scale. SPSS22 was used to analyze the data., Results: The results revealed that the mean frequency and intensity of moral distress were 44.42 ± 17.67 and 49.45 ± 17.11, respectively. The mean ethical climate was 92.21 ± 17.52 and the FATCOD was 89.75 ± 9.08, indicating NICU nurses' positive perceptions of ethical climate and their favorable attitudes towards EOL care, respectively. The results showed a direct and significant relationship between ethical climate and the FATCOD (P = 0.003, r = 0.26)., Discussion: We suggest policymakers and managers design strategies for better ethical climate in hospitals and reduction of moral distress among nurses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Suicide is a major issue of concern for public health. It is estimated that suicide accounts for 700,000 deaths every year. A personal history of one or more suicide attempts is the most important determinant of suicide among the general population. This study aimed to assess the major risk factors associated with suicidal behaviors among Iranian employees in a medical setting., Methods: In this study, 3,913 employees of Tehran University of Medical Sciences who participated in the employees' cohort study conducted by the university were recruited. Suicidal behaviors (SBs) and their associated risk factors were evaluated using the World Mental Health Composite International Diagnostic Interview (CIDI) Version 3.0. Univariate and multivariate logistic regressions were performed to identify the determinants of SBs among the participants, and crude and adjusted odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated., Results: Overall, 49.6% of respondents ( n = 1,939) reported that they were tired of life and thinking about death. The lifetime prevalence rate of suicidal ideation (SI) was 8.1% ( n = 317), that of suicide planning (SP) was 7.3% ( n = 287), and that of suicide attempts (SA) was 3.1% ( n = 122). Being female (OR: 1.87, CI: 1.64-2.12), being divorced (OR: 3.13, CI: 1.88-5.22), having a low level of education (OR: 1.57, CI: 1.15-2.14), and working in clinical and medical services (OR: 1.25, CI: 1.09-1.43) were associated with being tired of life and thinking about death. These factors were also associated with SI, SP, and SA., Discussion: These findings highlight the need to prioritize mental health for suicide prevention, especially for high-risk groups, in workplace mental health promotion programs and policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rezaei, Mohammadi, Aghaei, Pouragha, Latifi and Keshavarz-Mohammadi.)

Background: Scant information exists on Iranian women's protective behaviors mainly constant condom use. Inconsistent condom use seems prevalent among women with substance use problems. We aimed to investigate risky sexual behaviors (RSBs) and condom use barriers in Iranian women with substance use disorders (SUDs)., Methods: In our cross-sectional study, we recruited 300 women who sought treatments for their SUDs from the active outpatient drug free (ODF) and Methadone Maintenance Therapy (MMT) centers in Tehran, Iran during 2017-2021. We used three batteries including demographic questionnaire, the Risky Sexual Behavior Questionnaire (RSBQ); and the Condom Barriers Scale (CBS). The statistical software R, analysis of variance post hoc and multivariate analysis of variance (MANOVA) logistic regression tests were used in data analysis., Results: The majority reported at least one lifetime experience of RSBs. Our results show that only 22% of the participants 'always' use condom in their sexual encounters. The lowest and highest subscale scores of the CBS were related to Sexual Experience (SE) (2.47 ± 0.86) and access/availability structure (3.52 ± 0.7), respectively. RSBs had negative significant association with Partner Barrier (PB) subscale scores (OR = 0.4; 95% CI: 0.22 to 0.73) and effect on SE subscale scores (OR= 0.54; 95% CI: 0.31 to 0.94)., Conclusion: RSBs was prevalent among our study population. RSBs and condom use barriers are significantly interwoven. The condom use barriers were highly associated with the types of sexual encounters such as group sex or casual sexual relations than specific mean of sexual performance (i.e. anal sex). Gender-specific RSBs, STIs/HIV/AIDS prevention program is recommended for women with SUDs., (Copyright © 2023 Mergati Khoei et al. Published by Tehran University of Medical Sciences.)

Background: While self-rated health (SRH) and quality of life (QoL) has been associated with substance use disorders (SUDs) in sex-working populations, little is known about this association in Iran. This study aimed to assess QoL and SRH in Iranian female sex workers (FSWs) in Tehran., Method: FSWs were recruited using convenience sampling methods from substance abuse treatment centers in Tehran that exclusively provided services for women. Participants completed an interviewer-administered demographic questionnaire in Persian and the Iranian version of the Short Form Health Survey (SF-36). Descriptive analyses, means and standard deviations; frequency and percentages, t-test and one-way ANOVA, and Chi-square tests were utilized to analyze the data., Results: The mean age among 161 participants clinically diagnosed with SUD was 34.09 years (SD 7.97; range: 18-57). The total mean QoL score was 41.03 (SD: 12.92). The highest and lowest mean scores were observed in the physical functioning (52.23) and role emotional (26.64) dimensions, respectively. Significant differences (p < 0.05) in QoL were observed according to education and marital status, and the average QoL score was lower in women who reported permanent marriages and women who were illiterate. The average score of QoL was significantly higher in employed women. Overall, 51.6% of the women rated their health as sub-optimal, with divorced participants and women who were illiterate more likely to rate their health as sub-optimal (p < 0.05)., Conclusion: Results emphasize the need for mental, physical, and sexual health screening and gender-specific interventions to improve QoL in this population. Further investigation may elucidate the consequences of poor SRH and QoL on SUD treatment adherence, sexual risk behavior, and morbidity and mortality in FSWs., (© 2023. The Author(s).)

Background: The outbreak of Coronavirus in late 2019 and its continuation in the following years has affected all human societies, government organizations, and health systems. Access to health services is an important issue during crises. The present study aimed to investigate the effect of the Covid-19 pandemic on the consumption of health services in the public sector compared to the private sector in Iran., Methods: The research population consisted of all insured individuals covered by Iran Health Insurance Organization in Fars province, which amounts to approximately 2,700,000 people. The required information including the utilization of laboratory, radiology, medicine, and hospitalization services was extracted on a monthly basis from February 2019 to February 2021. The Multiple Group Interrupted Time Series Analysis (MGITSA) was used for data analysis along with STATA.15 software., Results: According to the findings of MGITSA, in the short-term, the utilization of private laboratory, radiology, medication, and hospital admissions had decreased by approximately 18,066, 8210, 135,445, and 1086 times, respectively (P < 0.05). In the long-run, the use of laboratory and radiology services had increased by about 2312 and 514 times (P < 0.05), respectively. The comparison between the public and private sectors showed that in the short-term, the use of radiology services decreased by about 12,525, while the use of medication increased by about 91,471 times (P < 0.05). In the long-run, the use of laboratory services decreased by about 1514 times (P = 0.076) and no change was observed in the other services utilization (in public relative to private centers)., Conclusions: Utilization of health services in the public versus private centers, except for medication and hospitalization, significantly decreased in the short-term. However the utilization of most services returned to the usual trend in the long-term. The reduction in access to health services could impose a significant burden of various diseases, at least in the short-term, and increase health costs in the coming years., (© 2023. The Author(s).)

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6., Methods: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach., Results: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6., Conclusion: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype., (© 2023. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Background and Aims: The COVID-19 pandemic has provided preliminary evidence of the existence of health, social, and environmental inequalities. This inequality encompasses inadequate access to safe water, clean air, and wastewater management, as well as limited socioeconomic and educational opportunities. These issues have not received sufficient attention during the pandemic. The purpose of this narrative review is to provide a comprehensive summary and analysis of the existing literature on a specific topic, ultimately leading to a conclusion based on the evidence presented., Methods: The search methodology for this study involved conducting comprehensive searches of scientific databases, including PubMed, ScienceDirect, LILACS, and Google Scholar, from 2019 to 2023. The study focused on a specific theme and its relevant aspects related to global environmental health and society. Keywords such as COVID-19, inequities, and environmental health were used for searching. Additionally, the Boolean operator "AND" was used to combine these descriptors., Results: Unequal exposure to air pollution has been reported in Africa, as well as in large parts of Asia and Latin America, according to the data that has been obtained. The pandemic has also resulted in a surge in healthcare waste generation, exacerbating the environmental impact of solid waste. Furthermore, there is evidence indicating significant disparities in the severe lack of access to sanitation services between developing nations and low-income regions. The issues related to water availability, accessibility, and quality are subject to debate. It has been reported that SARS-CoV-2 is present not only in untreated/raw water, but also in water bodies that act as reservoirs. Moreover, insufficient education, poverty, and low household income have been identified as the most significant risk factors for COVID-19 infection and mortality., Conclusion: It is evident that addressing socio-environmental inequality and striving to narrow the gap by prioritizing vulnerable populations are imperative., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

TbMex67 is the major mRNA export factor known to date in trypanosomes, forming part of the docking platform within the nuclear pore. To explore its role in co-transcriptional mRNA export, recently reported in Trypanosoma brucei, pulse labelling of nascent RNAs with 5-ethynyl uridine (5-EU) was performed with cells depleted of TbMex67 and complemented with a dominant-negative mutant (TbMex67-DN). RNA polymerase (Pol) II transcription was unaffected, but the procyclin loci, which encode mRNAs transcribed by Pol I from internal sites on chromosomes 6 and 10, showed increased levels of 5-EU incorporation. This was due to Pol I readthrough transcription, which proceeded beyond the procyclin and procyclin-associated genes up to the Pol II transcription start site on the opposite strand. Complementation by TbMex67-DN also increased Pol I-dependent formation of R-loops and γ-histone 2A foci. The DN mutant exhibited reduced nuclear localisation and binding to chromatin compared to wild-type TbMex67. Together with its interaction with chromatin remodelling factor TbRRM1 and Pol II, and transcription-dependent association of Pol II with nucleoporins, our findings support a role for TbMex67 in connecting transcription and export in T. brucei. In addition, TbMex67 stalls readthrough by Pol I in specific contexts, thereby limiting R-loop formation and replication stress., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

In this study, two series of novel 1,4-benzothiazine-3-one derivatives with alkyl substitution (series 1: 4a-4f) and aryl substitution (series 2: 4g-4l) were designed and synthesized based on the chemical scaffolds of perampanel, hydantoins, progabide and etifoxine as anti-convulsant agents. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1 H NMR and 13 C NMR spectroscopy. Anti-convulsant effect of the compounds was examined through intraperitoneal pentylenetetrazol (i.p. PTZ) induced epilepsy mouse models. Compound 4h (4-(4-bromo-benzyl)- 4 H-benzo[b] [1,4] thiazin-3(4 H)-one) demonstrated a promising activity toward chemically-induced seizure experiment. Molecular dynamics simulation on GABA-Aergic receptors as a plausible mechanism were also done to achieve the binding and orientation of compounds in the active site of the target to evaluate the results of docking and experimental studies. The computational results were confirmed the biological activity. DFT study of 4c and 4h was performed on B3LYP/6-311 G ** level of theory. Reactivity descriptors such as HOMO, LUMO, electron affinity, ionization potential, chemical potential, hardness and softness were studied in detail and show that 4h has higher activity than 4c. Also, the frequency calculations were performed on the same level of theory and the results are in line with experimental data. Moreover, in silico ADMET properties were done to establish a relationship between the physiochemical data of the designed compounds and their in-vivo activity. Appropriate plasma protein binding and high blood-brain barrier penetration are the main features of desired in-vivo performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease-causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families., Methods: Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole-exome sequencing (WES) was undertaken in order to detect disease-causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013-2020., Results: Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM&#95;022041.3:c.1162del (p.Leu388Ter)], in a 7-year-old boy of family 1, and a likely pathogenic missense variant [NM&#95;022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN-1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory-motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features., Conclusions: One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

MicroRNA production in tumorigenesis is dysregulated by a variety of processes, such as proliferation and removal of microRNA genes, aberrant transcriptional regulation of microRNAs, disrupted epigenetic alterations, and failures in the miRNA biogenesis machinery. Under some circumstances, miRNAs may act as tumorigenic and maybe anti-oncogenes. Tumor aspects such as maintaining proliferating signals, bypassing development suppressors, delaying apoptosis, stimulating metastasis and invasion, and promoting angiogenesis have been linked to dysfunctional and dysregulated miRNAs. MiRNAs have been found as possible biomarkers for human cancer in a great deal of research, which requires additional evaluation and confirmation. It is known that hsa-miR-28 can function as an oncogene or tumor suppressor in many malignancies, and it does this by modulating the expression of several genes and the downstream signaling network. MiR-28-5p and miR-28-3p, which originate from the same RNA hairpin precursor miR-28, have essential roles in a variety of cancers. This review outlines the function and mechanisms of miR-28-3p and miR-28-5p in human cancers and illustrates the miR-28 family's potential utility as a diagnostic biomarker for prognosis and early detection of cancers., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Toxoplasma gondii (T. gondii) is one of the most successful parasites in the world, because about a third of the world's population is seropositive for toxoplasmosis. Treatment regimens for toxoplasmosis have remained unchanged for the past 20 years, and no new drugs have been introduced to the market recently. This study, performed molecular docking to identify interactions of FDA-approved drugs with essential residues in the active site of proteins of T. gondii Dihydrofolate Reductase (TgDHFR), Prolyl-tRNA Synthetase (TgPRS), and Calcium-Dependent Protein Kinase 1 (TgCDPK1). Each protein was docked with 2100 FDA-approved drugs using AutoDock Vina. Also, the Pharmit software was used to generate pharmacophore models based on the TgDHFR complexed with TRC-2533, TgPRS in complex with halofuginone, and TgCDPK1 in complex with a bumped kinase inhibitor, RM-1-132. Molecular dynamics (MD) simulation was also performed for 100 ns to verify the stability of interaction in drug-protein complexes. Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis evaluated the binding energy of selected complexes. Ezetimibe, Raloxifene, Sulfasalazine, Triamterene, and Zafirlukast drugs against the TgDHFR protein, Cromolyn, Cefexim, and Lactulose drugs against the TgPRS protein, and Pentaprazole, Betamethasone, and Bromocriptine drugs against TgCDPK1 protein showed the best results. These drugs had the lowest energy-based docking scores and also stable interactions based on MD analyses with TgDHFR, TgPRS, and TgCDPK1 drug targets that can be introduced as possible drugs for laboratory investigations to treat T. gondii parasite infection., (© 2023. The Author(s).)

Breast cancer is a molecularly heterogeneous disease and the most common female malignancy. In recent years, therapy approaches have evolved to accommodate molecular diversity, with a focus on more biologically based therapies to minimize negative consequences. To regulate cell fate in human breast cells, the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors. This pathway regulates tissue size, regeneration, and healing, as well as the survival of tissue-specific stem cells, proliferation, and apoptosis in a variety of organs, allowing for cell differentiation. Hippo signaling is mediated by the kinases MST1, MST2, LATS1, and LATS2, as well as the adaptor proteins SAV1 and MOB. These kinases phosphorylate the downstream effectors of the Hippo pathway, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ), suppressing the expression of their downstream target genes. The Hippo signaling pathway kinase cascade plays a significant role in all cancers. Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer. In recent years, small noncoding RNAs, or microRNAs, have been implicated in the development of several malignancies, including breast cancer. The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast, on the other hand, remain poorly understood. In this review, we focused on highlighting the Hippo signaling system, its key parts, its importance in breast cancer, and its regulation by miRNAs and other related pathways., Competing Interests: The authors declare no potential conflict of interests., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background and Methods: Colorectal cancer (CRC) is considered one of the most common malignancies worldwide. The diagnosis and prognosis of the patients are very poor. In this study, we used in-silico analysis and experimental techniques to investigate novel co-expression genes and their associated miRNA networks in CRC. For this purpose, we conducted a comprehensive transcriptome analysis using online bulk and single-cell RNA-seq datasets. We then validated the results on tissue samples from cancerous and adjacent normal tissues from CRC patients by RT-qPCR., Results: Using a weighted gene co-expression network algorithm, we identified SLC4A4 as a significantly downregulated hub gene in the CRC. The single-cell analysis indicated that the expression level of SLC4A4 in Paneth cells is higher than in other cell populations. Further computational analysis suggested hsa-miR-223-3p and hsa-miR-106a-5p as two specific hub-miRNAs for the SLC4A4 gene. RT-qPCR analysis showed a 2.60-fold downregulation of SLC4A4. Moreover, hsa-miR-223-3p and hsa-miR-106a-5p showed an increased expression level of 5.58-fold and 9.66-fold in CRC samples, respectively. Based on the marginal model analysis, by increasing the expression of hsa-miR-106a-5p, the average expression of the SLC4A4 gene significantly decreased by 103 units. Furthermore, ROC curves analysis indicated statistically significant for diagnostic ability of SLC4A4 (AUC: 0.94, Sensitivity: 95.5%, Specificity: 95.5%) and hsa-miR-106a-5p (AUC: 0.72, Sensitivity: 72.7%, Specificity: 100%)., Conclusion: This study provides a framework of co-expression gene modules and miRNAs of CRC, which identifies some important biomarkers for CRC pathogenicity and diagnosis. Further experimental evidence will be required to support this study and validate the precise molecular pathways., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Biofilm is considered as a community of microorganisms in which cells adhere to each other on surfaces in a self-produced matrix of extracellular polymer compounds. In recent years, efforts to use the beneficial aspects of biofilm in probiotic research have intensified. In this study, probiotic biofilms of Lactiplantibacillus plantarum and Lacticaseibacillus rhamnosus were manufactured using milk and transferred to yogurt in whole and pulverized forms to test in real food conditions. Survival was assessed during 21 days of storage time as well as gastrointestinal conditions. The results indicated that Lp. plantarum and Lc. rhamnosus can form a very desirable and strong biofilm that can have a good protective effect on the survival of these bacteria in probiotic yogurt during processing, storage, and gastrointestinal conditions, in a way that, after 120 min of treatment in high acidic gastrointestinal conditions (pH 2.0), the survival rate decreased by only 0.5 and 1.1 log CFU/ml. Probiotic biofilm can be used as a natural way of utilizing bacteria in biotechnology and fermentation, which is an excellent way to increase the utility of probiotics., Competing Interests: The authors declare no conflict of interests., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples., Competing Interests: JK, ZR, TK, BM, MM No competing interests declared, (© 2023, Karimi Abadchi et al.)

Heart disease is the leading cause of death worldwide and imposes a significant burden on healthcare systems globally. A major hurdle to the development of more effective therapeutics is the reliance on animal models that fail to faithfully recapitulate human pathophysiology. The predictivity of in vitro models that lack the complexity of in vivo tissue remain poor as well. To combat these issues, researchers are developing organ-on-a-chip models of the heart that leverage the use of human induced pluripotent stem cell-derived cardiomyocytes in combination with novel platforms engineered to better recapitulate tissue- and organ-level physiology. The integration of novel biosensors into these platforms is also a critical step in the development of these models, as they allow for increased throughput, real-time and longitudinal phenotypic assessment, and improved efficiency during preclinical disease modeling and drug screening studies. These platforms hold great promise for both improving our understanding of heart disease as well as for screening potential therapeutics based on clinically relevant endpoints with better predictivity of clinical outcomes. In this review, we describe state-of-the-art heart-on-a-chip platforms, the integration of novel biosensors into these models for real-time and continual monitoring of tissue-level physiology, as well as their use for modeling heart disease and drug screening applications. We also discuss future perspectives and further advances required to enable clinical trials-on-a-chip and next-generation precision medicine platforms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Deok-Ho Kim is a scientific founder and equity holder of Curi Bio. Deok-Ho Kim reports a relationship with Curi Bio that includes: board membership, consulting or advisory, equity or stocks, funding grants, and travel reimbursement., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Azoles are the famous and widespread scaffold in the pharmaceutical industry due to their wide range of activities, high efficacy, good tolerability, and oral availability. Furthermore, azole derivatives have attracted attention as potent antimicrobial agents., Introduction: The purpose of this review is to provide an overview of pharmacological aspects of the main scaffolds of azoles, including imidazole, benzimidazole, triazole, and tetrazole, which possess antimicrobial activity, reported from 2016 to 2020, as well as all of our publication in this field. In addition, we discuss the relationship between structure and activity and molecular docking studies of the azole derivatives to provide critical features and valuable information for the synthesis of novel azole compounds with desirable biological activities. The presented structures in this review have been tested against several bacteria and fungi, such as E. coli and C. albicans, which have been common in all of these studies., Results: A comparison of the reported MIC for tested compounds showed fluconazole base structures as the most active antifungal agents, and triazole derivatives bearing nitrophenyl and coumarin moieties to have the most dominant antibacterial activity., Conclusion: Triazole and imidazole scaffolds are more important for designing antimicrobial compounds than other azole derivatives, like benzimidazole or tetrazole. All the most active compounds were observed to fulfill the Lipinski rule., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined., Objective: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA)., Methods: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project., Results: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease., Conclusions: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

The global spread of the coronavirus has generated one of the most critical circumstances forcing healthcare systems to deal with it everywhere in the world. The complexity of crisis management, particularly in Iran, the unfamiliarity of the disease, and a lack of expertise, provided the foundation for researchers and implementers to propose innovative solutions. One of the most important obstacles in COVID-19 crisis management is the lack of information and the need for immediate and real-time data on the situation and appropriate solutions. Such complex problems fall into the category of semi-structured problems. In this respect, decision support systems use people's mental resources with computer capabilities to improve the quality of decisions. In synergetic situations, for instance, healthcare domains cooperating with spatial solutions, coming to a decision needs logical reasoning and high-level analysis. Therefore, it is necessary to add rich semantics to different classes of involved data, find their relationships, and conceptualize the knowledge domain. For the COVID-19 case in this study, ontologies allow for querying over such established relationships to find related medical solutions based on description logic. Bringing such capabilities to a spatial decision support system (SDSS) can help with better control of the COVID-19 pandemic. Ontology-based SDSS solution has been developed in this study due to the complexity of information related to coronavirus and its geospatial aspect in the city of Tehran. According to the results, ontology can rationalize different classes and properties about the user's clinical information, various medical centers, and users' priority. Then, based on the user's requests in a web-based SDSS, the system focuses on the inference made, advises the users on choosing the most related medical center, and navigates the user on a map. The ontology's capacity for reasoning, overcoming knowledge gaps, and combining geographic and descriptive criteria to choose a medical center all contributed to promising outcomes and the satisfaction of the sample community of evaluators., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Monkeypox is a zoonotic virus that has recently affected different countries worldwide. On July 23, 2022, the WHO declared the outbreak of monkeypox as a public health emergency of international concern. Surveillance studies conducted in Central Africa in the 1980s and later during outbreaks in the same region showed smallpox vaccines to be clinically somewhat effective against Monkeypox virus. However, there is no specific vaccine against this virus. This research used bioinformatics techniques to establish a novel multi-epitope vaccine candidate against Monkeypox that can induce a strong immune response. Five well-known antigenic proteins (E8L, A30L, A35R, A29L, and B21R) of the virus were picked and assessed as possible immunogenic peptides. Two suitable peptide candidates were selected according to bio-informatics analysis. Based upon in silico evaluation, two multi-epitope vaccine candidates (ALALAR and ALAL) were built with rich-epitope domains consisting of high-ranking T and B-cell epitopes. After predicting and evaluating the 3D structure of the protein candidates, the most efficient 3D models were considered for docking studies with Toll-like receptor 4 (TLR4) and the HLA-A * 11:01, HLA-A*01:01, HLA-A*02:01, HLA-A*03:01, HLA-A*07:02, HLA-A*15:01, HLA-A*30:01 receptors. Subsequently, molecular dynamics (MD) simulation of up to 150 nanoseconds was employed to assess the durability of the interaction of the vaccine candidates with immune receptors. MD studies showed that M5-HLA-A*11:01, ALAL-TLR4, and ALALAR-TLR4 complexes were stable during simulation. Analysis of the in silico outcomes indicates that the M5 peptide and ALAL and ALALAR proteins may be suitable vaccine candidates against the Monkeypox virus.Communicated by Ramaswamy H. Sarma.

In the current study, twenty-five indole-carbohydrazide derivatives linked to different aryl substitutions were rationally designed and synthesized. The structures of all derivatives were confirmed using different spectroscopic techniques including 1 H NMR, 13 C NMR, Mass spectrometry, and elemental analysis. The tyrosinase inhibitory activities of all synthetic compounds exhibited IC 50 values in the range of 0.070 to > 100 μM. Structure-activity relationships showed that compounds 4f (R = 4-OH, IC 50  = 0.070 μM), 8f (R = 4-OH, IC 50  = 0.072 μM), and 19e (IC 50  = 0.19 μM) with para-OH substituent at the R position was found to be the most active members of all three tested series. Kinetic studies exhibited that compounds 4f, 8f, and 19e are mixed-type inhibitors. Furthermore, toxicity and cell-based anti-melanogenesis assessments were performed on the most potent derivatives and it was shown that 4f, 8f, and 19e had no toxicity at 8 µM and reduced the percent of melanin content to 68.43, 72.61, 73.47 at 8 μM, respectively. In silico analyses of absorption, distribution, metabolism, and excretion (ADME) profile of synthesized compounds showed that these molecules followed drug-likeness rules and acceptable predictive ADMET features. Results of the docking study were almost in line with biological results with ChemPLP values of 53.56 to 79.33. Also, the docking study showed the critical interactions of potent inhibitors with the active site of the enzyme which affects the potency of the synthesized hybrids. Based on molecular dynamic simulations, compound 4f exhibited pronounced interaction with the critical residues of the tyrosinase active site so that the indole ring participated in H-bond interaction with Gly281 and 4-hydroxy benzylidene recorded another H-bond interaction with Asp289 plus hydrophobic interactions with Phe292. Hydrazide linker also exhibited three H-bond interactions with His263 and Gly281., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Herein, we reported the synthesis of nineteen novel 1,2,4-triazole derivatives including 1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl) propan-1-ones (7a-e), 1-(1,3-diphenylpropan-2-yl)-1H-1,2,4-triazole (8a-c) and 1,4-diphenyl-2-(1H-1,2,4-triazol-1-yl) butane-1,4-diones (10a-k). The structures of these derivatives were confirmed by spectroscopic techniques like IR, 1 H-NMR, Mass spectroscopy and Elemental analysis. The cytotoxic activities of the synthesized compounds were evaluated against three human cancer cell lines including MCF-7, Hela and A549 using MTT assay. Compounds 7d, 7e, 10a and 10d showed a promising cytotoxic activity lower than 12 μM against Hela cell line. The safety of these compounds was also, evaluated on MRC-5 as a normal cell line and relieved that most of the synthesized compounds have proper selectivity against normal and cytotoxic cancerous cell lines. Finally, molecular docking studies were also, done to understand the mechanism and binding modes of these derivatives in the binding pocket of aromatase enzyme as a possible target., (© 2022. The Author(s).)

Introduction: Gestational diabetes mellitus (GDM) is an important condition during pregnancy. The aim of the current study was to evaluate the effects of self-management education based on 5A model on the quality of life and blood glucose level of women with GDM., Methods: This quasi-experimental study was conducted on 54 pregnant women referred to the urban health care centers affiliated to the Gonabad University of Medical Sciences from March 2019 to March 2020 based on purposive sampling method. Participants were randomly allocated into intervention and control groups based on stratified random sampling using permuted block randomization method. The intervention group received self-management education program based on 5A model in five sessions during two months. Demographic data, blood glucose level, and diabetes quality of life (DQOL) questionnaire were collected for each participant. Data analysis was performed using the SPSS software version 16 and the level of statistical significance was set at 0.05., Results: Mean age of the participants was 33.11 ± 5.35 years old. At the end of the intervention, the mean blood glucose level of the participants in the intervention group was significantly lower compared to the control group (p < 0.001). The quality of life in the intervention group was significantly improved at the end of the intervention compared to the control group (p < 0.001)., Conclusions: Self-management education based on 5A model can effectively improve quality of life and blood glucose levels in women with GDM., (©2022 Pacini Editore SRL, Pisa, Italy.)

Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on different immunomodulation strategies for various delivery options and deliberate upon the outlook of such drug delivery platforms are conducted.

Background: The current study aimed to determine the seroprevalence of Toxoplasma gondii infection among HIV-positive patients and healthy subjects., Methods: This study was carried out on HIV-positive patients and healthy individuals in Southwest Iran. Five millilitres of venous blood samples were collected aseptically from each individual. Sera and buffy coats were isolated from each sample and evaluated for anti-Toxoplasma antibodies and T. gondii DNA using ELISA kit and real-time PCR, respectively. Statistical analysis was performed using SPSS 18 software., Results: Of 64 AIDS/HIV-positive patients, six (9.3%, 95% CI 7.2 to 11.3%) were seropositive for only IgG and five (7.8%, 95% CI 6.0 to 9.5%) were seropositive for both IgG and IgM. Moreover, among 64 healthy controls, 10 (15.6%, 95% CI 12.1 to 19.0%) were seropositive for only IgG and 2 (3.1%, 95% CI 2.4 to 3.7%) were seropositive for both IgG and IgM. Toxoplasma gondii DNA was detected in six samples (9.3%, 95% CI 7.2 to 11.3%) in the AIDS/HIV-positive patients group and eight samples (5.95%, 95% CI 4.6 to 7.2%) in the control group using real-time PCR. Consumption of undercooked meat was documented as an associated risk factor for T. gondii seropositivity in AIDS patients (OR 4.06, 95% CI 0.966 to 17.09; p=0.045)., Conclusions: Our findings showed a lower prevalence of Toxoplasma infection in AIDS/HIV-positive patients vs healthy controls; however, a considerable number of AIDS/HIV-positive patients were also seen to be at risk of toxoplasmosis. Based on the findings, screening and prophylaxis for toxoplasmosis should be implemented for all AIDS/HIV-positive patients in Southwest Iran., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background and Objectives: Phage therapy has gained interest as an alternative treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections. The purpose of this study was to isolate and characterize an effective bacteriophage against isolates of MRSA., Materials and Methods: Bacteriophage was isolated from hospital sewage. Lytic activity and the titers of phage lysates were measured using spot test and double-layer plaque assay. The phage characterization was determined through transmission electron microscopy. Adsorption rate, host range and stability tests were investigated. The latent period and burst size were estimated from a one-step growth curve. The effect of bacteriophage against MRSA biofilms was determined and Real-time PCR was used to assess the effects of the bacteriophage on the expression of the biofilm-associated genes., Results: TEM results showed that the phage resembled the Cystoviridae family. Its latent period was 30 min, corresponding to about 71/43 phage particles per infected cell. The phage had a broad host range and it was most stable at 37°C and pH 7. It was sensitive to NaCl concentrations. The expressions of the biofilm-associated genes were significantly reduced in the presence of the phage., Conclusion: The isolated phage was effective against MRSA strains and it can be an optional strategy of controlling biofilm development., (Copyright © 2022 The Authors. Published by Tehran University of Medical Sciences.)

Background: Self-rated health (SRH) indicator is widely used and recommended in health research as a standard indicator for measuring health in different populations. This paper reports SRH of employees at Tehran University of Medical Sciences (TUMS), Tehran, Iran; and its related factors., Methods: We used the TUMS Employee's Cohort Study (TEC) data, collected from September 2017 to August 2019. SRH of 2158 employees were assessed using a single question. Univariate and multivariate logistic regression were performed to determine factors associated with sub-optimal SRH., Results: Overall, 14.9% (n = 321) of respondents rated their health as sub-optimal. Differences were observed with subgroups. Women, lower socioeconomic status (SES), experiences of more economic fluctuation conditions and lower reading scores could predict sub-optimal SRH variations in crude and adjusted regression analyses. The age, social capital, work experience and employment status could predict sub-optimal SRH variations only in crude regression analyses ( P <0.05)., Conclusion: Differences in SRH report reflected differences in socioeconomic conditions. The biggest gap was observed between people of different SES (five times). Considering that SRH reflected socioeconomic characteristics of individuals, it may be considered as a quick, non-expensive, and simple way of identifying groups in need of addressing their social determinants of health., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Rezaei et al. Published by Tehran University of Medical Sciences.)