RORA and Autism in The Isfahan Population: Is There An Epigenetic Relationship.

OBJECTIVE Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptor- related orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region. This may thus explain a significant part of the molecular pathogenesis of autism. Therefore, we aimed to confirm this finding by implementing a case-control (experimental) study in the population of Isfahan. MATERIALS AND METHODS The methylation status of a 136 bp sequence of a GpG island (encompassing 13 CpG sites) in the RORA promoter region (positions -200 to -64) as an experimental study was examined in the lymphocyte cells of 30 autistic children after sodium bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay compared with normal children. Also, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to evaluate MCA-Meth analysis results. RESULTS This study revealed no methylation in the examined promoter regions in both autistic and normal children, with the melting curve of all studied samples being comparable to that of the non-methylated control. The results of MCA-Meth analysis were also consistent with qRT-PCR results. We therefore observed no significant difference in the levels of RORα transcripts in the blood lymphocytes between autistic and healthy children. CONCLUSION The methylation of the RORA promoter region may not be considered as a common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis of autism remains unclear in the population investigated

Decoding the genetics of speech and language: Genetic insight into the functional elements

زمینه و هدف: مدت زمان مدیدی است که تصور می‌شود توانایی انسان برای کسب قابلیت زبان توسط ساختار ژنتیکی او کد می‌شود. با این حال، تنها به تازگی شواهد ژنتیکی متعددی برای اثبات اساس ژنتیکی احتمالی ِزبان در دسترس است. در طول دهه گذشته، واریانت‌های ژنتیکی مختلفی شناسایی شده‌اند که ممکن است افراد را به جنبه‌های مختلف اختلالات زبان مستعد کنند. اختلالات زبان و گفتار طیف گسترده‌ای از شرایط با فنوتیپ‌های هتروژن و همپوشان را پوشش می‌دهند که می‌توانند علل پیچیده‌ی ژنتیکی و محیطی داشته باشند. ر‌وش بررسی: در این مطالعه مروری، جستجوی نظام ‌مندی در پایگاه‌های الکترونیکی معتبر (Googlescholar, Pubmed, Sciencedirect و Scopus) انجام شد و مقالات انگلیسی مرتبط با موضوع به وسیله‌ی انتخاب کلمات کلیدی زبان، ژنتیک، ژن FOXP2، ژن‌های کاندید و غیره مورد جستجو و استخراج قرار گرفتند. یافته ‌ها: در این مقاله‌ی مروری، بحث می‌کنیم که چگونه شناسایی و مطالعه‌ی ژن‌های خاص، از جمله: FOXP2، CNTNAP2، FOXP1، DCDC2، DYX1C1، ROBO1، KIAA0319، ATP2C2، CMIP، CYP19A1، SRPX2، MRPL19، C2ORF3 و DOCK4، می‌تواند درک ما از سبب‌شناسی اختلالات تکلم و اساس بیولوژیکی اکتساب زبان را افزایش دهد. نتیجه ‌گیری: شناسایی ژن‌های مرتبط با فنوتیپ‌های زبان و تکلم، و توصیف عملکردهای طبیعی و نابجای این ژن‌ها در سال‌های اخیر، جزئیات پیچیده‌ی مکانیسم‌های مولکولی و شناختی را مشخص کرده و دیدگاه ارزشمندی از اساس بیولوژیکی زبان ارائه کرده است

An overview on the evolution of language and genetics of speech disorders

Language, as an exclusive salient of human kind, is the requisite of development and formation of the human society; thus, it is at the topmost of human evolutionary features. Language and speech can be studied in various fields such as biology. Biolinguistics is an interdisciplinary field in which biological development of language is studied. It aims to find the functioning cycle in mind that enables humans to perceive the principles and bases of language. Language genetics, a subfield of biolinguistics, traces genetic factors in the formation and perception of language. Although a variety of theories have been introduced to explain the origins of language, considering recent studies, acquiring essential genetic abilities for speaking are undoubtedly of the most crucial necessities of this skill. Researchers have recently found defective genes in a wide spectrum of language disorders, through which they strongly confirm that speech systems rely on these genes to function properly. However, there is no report on a study which answers this question clearly: considering the origins of language and human evolution, is the proper function of genes, genetic structures, and general requirements necessary for speaking? The evolution of language and genetics of speech disorders along with the outstanding improvements and recent studies are discussed in this review article. © 2014, Isfahan University of Medical Sciences(IUMS). All rights reserved

RORA and Autism in Isfahan population: Is there an epigenetic relationship

Objective: Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptorrelated orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region. This may thus explain a significant part of the molecular pathogenesis of autism. Therefore, we aimed to confirm this finding by implementing a case-control (experimental) study in the population of Isfahan. Materials and Methods: The methylation status of a 136 bp sequence of a GpG island (encompassing 13 CpG sites) in the RORA promoter region (positions - 200 to - 64) as an experimental study was examined in the lymphocyte cells of 30 autistic children after sodium bisulfite treatment using the melting curve analysis-methylation (MCA-Meth) assay compared with normal children. Also, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was used to estimate the level of mRNA transcripts and to evaluate MCA-Meth analysis results. Results: This study revealed no methylation in the examined promoter regions in both autistic and normal children, with the melting curve of all studied samples being comparable to that of the non-methylated control. The results of MCA-Meth analysis were also consistent with qRT-PCR results. We therefore observed no significant difference in the levels of RORα transcripts in the blood lymphocytes between autistic and healthy children. Conclusion: The methylation of the RORA promoter region may not be considered as a common epigenetic risk factor for autism in all populations. Hence, the molecular pathogenesis of autism remains unclear in the population investigated

The Effect of Music Therapy on Anxiety and Vital Signs of Patients with Acute Coronary Syndrome: A Study in the Cardiac Care Unit of Vali-Asr Hospital, Eghlid, Iran

Background: Acute coronary syndrome is an emergency situation, characterized by a sudden decrease of blood flow to the heart and chest pain during a heart attack or unstable angina. High levels of anxiety increases mortality risk up to three times. The aim of this study was to determine the effect of music therapy on anxiety level and vital signs of patients with acute coronary syndrome admitted in the coronary care unit of Vali- Asr hospital, in Eghlid city. Methods: This clinical trial was conducted on 70 acute coronary syndrome patients who were eligible for the study during 2011-2012. Anxiety level was measured by the standard Spielberger Questionnaire and vital signs of patients were recorded before and after the intervention. Data were analyzed through SPSS18 and using mean, percentage, standard deviation, independent and paired t- test. Results: Music had no effect on vital signs but significantly reduced anxiety level (P=0.049). Anxiety was significantly higher in females, but showed no significant relationship with age and education. There was no significant relationship between age, sex and education with respiratory rate, heart rate and systolic or diastolic blood pressure. Conclusions: Music as an easy and low cost intervention without any complication can be used to reduce anxiety in patients in Coronary Care Units

Estudio experimental y numérico de la estabilidad de la pendiente aguas arriba en un embalse de presas de tierra en condiciones de extracción rápida

The rapid ‎drawdown of the dam reservoir is one of the most common situations occurring in the lifetime of a dam. For this reason, one of the main factors in the design of the upstream slope is the rapid drainage of the reservoir. In this case, the upstream slope is in a critical condition and the slope may be unstable. When the water surface in the reservoir is drawdown suddenly, the water level in the dam body does not decrease at the same time as the reservoir water level. The analysis of seepage from the earth dam body and calculation of the water loss play an important role in calculating the amount of pore water pressure, and, consequently, the stability analysis of the dam body. In addition, any seepage analysis is dependent on the hydraulic properties of the dam materials. In order to investigate the effect of hydraulic conductivity on the rapid drawdown of water level and the seepage, an experimental model was constructed of an earth dam. By accurate measurement of hydraulic parameters of the materials in saturated and unsaturated media, the flow through this model was modeled using a disk penetrometer by seep/w software. The results were then compared with the observed data.The rapid ‎drawdown of the dam reservoir is one of the most common situations occurring in the lifetime of a dam. For this reason, one of the main factors in the design of the upstream slope is the rapid drainage of the reservoir. In this case, the upstream slope is in a critical condition and the slope may be unstable. When the water surface in the reservoir is drawdown suddenly, the water level in the dam body does not decrease at the same time as the reservoir water level. The analysis of seepage from the earth dam body and calculation of the water loss play an important role in calculating the amount of pore water pressure, and, consequently, the stability analysis of the dam body. In addition, any seepage analysis is dependent on the hydraulic properties of the dam materials. In order to investigate the effect of hydraulic conductivity on the rapid drawdown of water level and the seepage, an experimental model was constructed of an earth dam. By accurate measurement of hydraulic parameters of the materials in saturated and unsaturated media, the flow through this model was modeled using a disk penetrometer by seep/w software. The results were then compared with the observed data

Analysis of the Effects of Economic Variables on the Price of Cement and Forecasting its Price Trend

The present study aims to identify the variables affecting the price of cement and provide in- and out-of-sample forecasts using monthly data from 2019:03 to 2023:02 and a vector autoregression (VAR) model. In this regard, according to the results of the Johansen-Juselius cointegration test, the long-term relationship between the variables was confirmed. Then, the long-term and short-term models were estimated, and the error correction coefficient was -0.0858. In the next stage, based on the results of impulse response functions, exchange rate and construction input price index shocks (respectively with a positive effect of 8 and 6.8 percent in the standard form) have been more effective than other model variables on the fluctuations of cement price. The results of variance decomposition also showed that the construction input price index, energy cost, and exchange rate are important in explaining the price of cement. Finally, we estimated in-sample and out-of-sample forecasts. Based on the forecast evaluation criteria, our founding research model can accurately predict the price trend of cement

A Post-Marketing Surveillance Study to Evaluate the Safety Profile of AlvotereⓇ (Docetaxel) in Iranian Patients Diagnosed with Different Types of Cancers Receiving Chemotherapy

Background Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non–small cell lung cancer, and prostate cancer. Objective This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel. Methods Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets. Findings A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants’ mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher (P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens. Conclusions The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX) © 2022 Elsevier HS Journals, Inc

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18 : a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe