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The current study concerns with studying some mechanical and physical properties of different samples taken from Unplasticized Polyvinyl Chloride (UPVC) pipes used in sewage purpose. Impact strength, compressive strength, shore-D hardness, and diffusion coefficient also were calculated for the samples immersed in different solutions (Wastewater, HCl-0.5N, and Tape water) for four months. Results showed that the mechanical properties of samples were affected by solutions and reduced by (3 – 5)% for impact strength and (10%) for compressive strength. Values for diffusion coefficient (D) were calculated, it was found that (HCl-0.5N) had a higher value, followed by wastewater then tape water. No cracks were observed, and there were no changes in sample’s dimensions after immersion in solutions.

This study investigates the activity concentration of natural radionuclides in a diverse range of food samples in the Koya district markets food baskets, including both domestic and imported products. The samples cover annual crops (e.g. coffee, tea, kidney beans), tree nuts (e.g. almonds, pistachios), and other items (e.g. beef, fish, milk) by using a high-purity germanium (HPGe) detector. This research addresses a notable gap by providing baseline data on radionuclide concentrations and assessing potential health risks. Average activity concentrations for ²²⁶Ra, ²³²Th, and ⁴⁰K were 0.943, 0.367, and 191.8 Bq kg -1 , respectively. Radium equivalent activity values ranged from 2.88-58.48 Bq kg -1 , all below the safety limit. The average excess lifetime cancer risk (ELCR) was 0.154 mSv a -1 , indicating safety for most samples, though coffee and tea showed higher levels. This study provides new data crucial for future research and regulatory monitoring, underscoring the need for further investigation into geological impacts on radionuclide levels.

Alcohol consumption and addiction remain global health concerns, with significant loss of productivity, morbidity, and mortality. Drosophila melanogaster , a widely used model organism, offers valuable insights into the genetic and neuronal mechanisms underlying ethanol-induced behaviors (EIBs) such as sedation, recovery, and tolerance. This narrative review focuses on studies in the Drosophila model system suggesting an association between circadian rhythm genes as modulators of ethanol tolerance. Mutations in these genes disrupt both the circadian cycle and tolerance, underscoring the interplay between circadian rhythm and ethanol processing although the exact mechanisms remain largely unknown. Additionally, genes involved in stress response, gene expression regulation, neurotransmission, and synaptic activity were implicated in ethanol tolerance modulation. At the neuronal level, recent studies have highlighted the involvement of corazonin (CRZ) and neuropeptide F (NPF) neurons in modulating EIBs. Understanding the temporal dynamics of tolerance development is crucial for describing the molecular basis of ethanol tolerance. Ultimately, insights gained from Drosophila studies hold promise for elucidating the neurobiological underpinnings of alcohol use disorders and addiction, contributing to more effective interventions and treatments.

Background and aim AI is revolutionizing medical education by offering innovative tools and simulations that augment traditional teaching methods. This study explored the perceptions and expectations of medical students in the Kurdistan region, Iraq, regarding AI integration in medical education. Methods A cross-sectional online survey collected data from 224 medical students over four months. A descriptive analysis was conducted to present the student's attitudes.  Results In total, 224 medical students responded to the online survey. The majority of them were female (n=129; 57.6%), while 95 were male (42.4%). Additionally, most of the participants were in stage 4 (54 (24.1%); stage 1, 48 (21.4%); and stage 2, 43 (19.2%). In terms of measuring students' perceptions of AI integration in medical education, 186 (83%) of the students wanted to use smartphones and tablets, and 38 (17%) of them reported wanting hard copies. In addition, 112 (50%) of the medical students considered themselves experts in using AI and 98 (43.8%) did not know exactly what AI was used; however, only a few of them (6.3%) did not use AI. Few patients reported using Manikins instead of real patients (42 (18.8%)), while 140 (62.5%) reported that they could be used but not an alternative. Conclusion While many agree that digital tools and simulations are useful teaching tools, they are frequently viewed as adjunctive approaches. Better integration and training are required for the infrequent use of AI tools in medical education., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethics Committee of Koya University issued approval 3/15/23-1-2024. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hawezy et al.)

Familial Dysautonomia (FD) is an autosomal recessive disorder caused by a splice site mutation in the gene ELP1, which disproportionally affects neurons. While classically characterized by deficits in sensory and autonomic neurons, neuronal defects in the central nervous system have also been described. Although ELP1 expression remains high in the normal developing and adult cerebellum, its role in cerebellar development is unknown. To explore the role of Elp1 in the cerebellum, we knocked out Elp1 in cerebellar granule cell progenitors (GCPs) and examined the outcome on animal behavior and cellular composition. We found that GCP-specific conditional knockout of Elp1 (Elp1 cKO ) resulted in ataxia by 8 weeks of age. Cellular characterization showed that the animals had smaller cerebella with fewer granule cells. This defect was already apparent as early as 7 days after birth, when Elp1 cKO animals also had fewer mitotic GCPs and shorter Purkinje dendrites. Through molecular characterization, we found that loss of Elp1 was associated with an increase in apoptotic cell death and cell stress pathways in GCPs. Our study demonstrates the importance of ELP1 in the developing cerebellum, and suggests that loss of Elp1 in the GC lineage may also play a role in the progressive ataxia phenotypes of FD patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: Falls are a common cause of fractures in older adults. This study aimed to investigate the factors associated with spontaneous falls among people aged ≥ 60 years in southern Iran., Methods: The baseline data of 2,426 samples from the second stage of the first phase of a prospective cohort, the Bushehr Elderly Health (BEH) program, were included in the analysis. A history of spontaneous falls in the year before recruitment was measured by self-report using a standardized questionnaire. Demographic characteristics, as well as a history of osteoarthritis, rheumatoid arthritis, low back pain, Alzheimer's disease, epilepsy, depression, and cancer, were measured using standardized questionnaires. A tandem gait (heel-to-toe) exam, as well as laboratory tests, were performed under standard conditions. A multiple logistic regression model was used in the analysis and fitted backwardly using the Hosmer and Lemeshow approach., Results: The mean (standard deviation) age of the participants was 69.34 (6.4) years, and 51.9% of the participants were women. A total of 260 (10.7%, 95% CI (9.5-12.0)%) participants reported a spontaneous fall in the year before recruitment. Adjusted for potential confounders, epilepsy (OR = 4.31), cancer (OR = 2.73), depression (OR = 1.81), low back pain (OR = 1.79), and osteoarthritis (OR = 1.49) increased the risk of falls in older adults, while the ability to stand ≥ 10 s in the tandem gait exam (OR = 0.49), being male (OR = 0.60), engaging in physical activity (OR = 0.69), and having high serum triglyceride levels (OR = 0.72) reduced the risk of falls., Conclusion: The presence of underlying diseases, combined with other risk factors, is significantly associated with an increased risk of falls among older adults. Given the relatively high prevalence of falls in this population, it is crucial to pay special attention to identifying and addressing these risk factors., (© 2024. The Author(s).)

Background: Low BMD is a common problem in major thalassaemia patient, but the use of DXA in chronic disease children with smaller bones, has some problems. Utilizing bone mineral apparent density (BMAD) helps in preventing this obstacle. Testing the usefulness of this method in resolving the effects of bone size on BMD by comparing the BMD and BMAD of our thalassemics with results of our healthy ones, is our goal., Methods: Sample size was 110 cases with mean age of 9.6 ± 4.3 y/o and contained 73 males. Gauge of BMDs done by dual x-ray absorptiometry. Then BMAD was calculated. We did comparison of BMDs and BMADs results of thalassemic children with results of healthy Iranian pediatrics., Results: Mean of femoral BMD and BMAD, spinal BMD and BMAD was 0.579±0.134 g/cm2, 0.162±0.096 g/cm3, 0.563±0.118 g/cm2 and 0.107±0.015, respectively. When results of 9-18 patients compared with BMDs and BMADs of normal children, BMD of femur and BMD and BMAD of spine of patients found significantly lower (P-values, 0.003, <0.001, <0.001, respectively). BMAD of femur of patients was not significantly different from normals., Conclusion: When bone mineral density of femur modifies by bone mineral apparent density formula, the remarkable difference between BMD of patients and normals; vanishes. Utilizing bone mineral apparent density helps in interpretation of femoral dual X-ray absorptiometry at least in thalassemic patients. As the results of vertebrae, after modification by calculating BMAD, remains significantly different, we cannot bring forward BMAD for mentioned aim in the spine of thalassemics., Competing Interests: All authors have no conflicts of interest., (© The Author(s).)

The levels of naturally occurring radionuclides in soil, grass, and milk were measured in this study in order to calculate the transfer factor of radionuclides from soil to grass and grass to milk obtained from Erbil governorate in Iraq. High efficiency gamma spectrometry used for the measurement. It has been determined that the mean activity concentrations of 232 Th, 226 Ra, and 40 K are 3.08, 8.37, and 253 BqKg -1 in soil, 0.5, 0.39, and 203.05 BqKg -1 , in grass, and 0.29, 0.084, and 29.69 BqL -1 , in milk, respectively. For soil to grass, the transfer factor values for 232 Th, 226 Ra, and 40 K were found to be 0.18, 0.052, and 0.84, respectively, for soil to grass. For grass to milk, the transfer factor values for 232 Th, 226 Ra, and 40 K were found to be 0.45, 0.166, and 0.11 dayL -1 , respectively. The average transfer factor for 232 Th, 226 Ra, and 40 K in all samples were lower than the world average value., 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.)

Kidney cancer (KC) is a prevalent cancer worldwide. The incidence and mortality rates of KC have risen in recent decades. The quality of care provided to KC patients is a concern for public health. Considering the importance of KC, in this study, we aim to assess the burden of the disease, gender and age disparities globally, regionally, and nationally to evaluate the quality and inequities of KC care. The 2019 Global Burden of Disease study provides data on the burden of the KC. The secondary indices, including mortality-to-incidence ratio, disability-adjusted life years -to-prevalence ratio, prevalence-to-incidence ratio, and years of life lost-to-years lived with disability ratio, were utilized. These four newly merged indices were converted to the quality-of-care index (QCI) as a summary measure using principal component analysis. QCI ranged between 0 and 100, and higher amounts of QCI indicate higher quality of care. Gender disparity ratio was calculated by dividing QCI for females by males to show gender inequity. The global age-standardized incidence and mortality rates of KC increased by 29.1% (95% uncertainty interval 18.7-40.7) and 11.6% (4.6-20.0) between 1990 and 2019, respectively. Globally, the QCI score for KC increased by 14.6% during 30 years, from 71.3 to 81.6. From 1990 to 2019, the QCI score has increased in all socio-demographic index (SDI) quintiles. By 2019, the highest QCI score was in regions with a high SDI (93.0), and the lowest was in low SDI quintiles (38.2). Based on the World Health Organization regions, the QCI score was highest in the region of America, with Canada having the highest score (99.6) and the lowest in the African Region, where the Central African Republic scored the lowest (17.2). In 1990, the gender disparity ratio was 0.98, and in 2019, it was 0.97 showing an almost similar QCI score for females and males. Although the quality of care for KC has improved from 1990 to 2019, there is a significant gap between nations and different socioeconomic levels. This study provides clinicians and health authorities with a global perspective on the quality of care for KC and identifies the existing disparities., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There has been an increase in the number of women using marijuana whilst pregnant. Previous studies have shown that children with prenatal marijuana exposure have developmental deficits in memory and decreased attentiveness. In this study, we assess whether prenatal marijuana exposure is associated with alterations in brain regional morphometry and functional and structural connectivity in adolescents. We downloaded behavioural scores and subject image files from the Adolescent Brain Cognitive Development SM Study. A total of 178 anatomical and diffusion magnetic resonance imaging files (88 prenatal marijuana exposure and 90 age- and gender-matched controls) and 152 resting-state functional magnetic resonance imaging files (76 prenatal marijuana exposure and 76 controls) were obtained. Behavioural metrics based on the parent-reported child behavioural checklist were also obtained for each subject. The associations of prenatal marijuana exposure with 17 subscales of the child behavioural checklist were calculated. We assessed differences in brain morphometry based on voxel-based and surface-based morphometry in adolescents with prenatal marijuana exposure versus controls. We also evaluated group differences in structural and functional connectivity in adolescents for region-to-region connectivity and graph theoretical metrics. Interactions of prenatal marijuana exposure and graph networks were assessed for impact on behavioural scores. Multiple comparison correction was performed as appropriate. Adolescents with prenatal marijuana exposure had greater abnormal or borderline child behavioural checklist scores in 9 out of 17 subscales. There were no significant differences in voxel- or surface-based morphometry, structural connectivity or functional connectivity between prenatal marijuana exposure and controls. However, there were significant differences in prenatal marijuana exposure-graph network interactions with respect to behavioural scores. There were three structural prenatal marijuana exposure-graph network interactions and seven functional prenatal marijuana exposure-graph network interactions that were significantly associated with behavioural scores. Whilst this study was not able to confirm anatomical or functional differences between prenatal marijuana exposure and unexposed pre-adolescent children, there were prenatal marijuana exposure-brain structural and functional graph network interactions that were significantly associated with behavioural scores. This suggests that altered brain networks may underlie behavioural outcomes in adolescents with prenatal marijuana exposure. More work needs to be conducted to better understand the prognostic value of brain structural and functional network measures in prenatal marijuana exposure., Competing Interests: The authors have conducted this research in the absence of any commercial, financial or personal relationships that would be considered a conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Osteoporotic fractures can result in significant health complications and an increased risk of death. Registry studies could provide better treatment options and improve patient outcomes by providing useful information about the disease. The present study describes the protocol for an osteoporosis registry in Iran., Materials and Methods: This registry is a prospective multicenter cohort study recruiting patients with osteoporosis from Iran. The inclusion criteria of the study are individuals diagnosed with primary or secondary osteoporosis according to the diagnostic criteria of the study; patients will be identified and recruited from outpatient clinics in this registry. All patients diagnosed with primary or secondary osteoporosis are the target population of the study. Our expected sample size is 1000 participants and the study will continue for at least 2 years. The measurements of the Iranian Osteoporosis Registry include four parts: (i) variables measured by the specific questionnaires package, (ii) bone mineral density (BMD, (iii) clinical examination, and (iv) lab data. The final questionnaire package includes "demographics information", "socioeconomic status", "lifestyle", "reproductive health", "medical history and medication", "Osteoporosis diagnosis gap", "Osteoporosis adherence and treatment gap", "fracture history and fall risk assessment", "FRAX ® tool ", "hospitalization and death outcomes", "low back pain", "hospitalization history", "attitude toward osteoporosis", "osteoporosis awareness", "osteoporosis related-performance", "quality of life (Iranian version of SF12 questionnaire )", and "food frequency questionnaire (FFQ)". Clinical examination of this registry includes anthropometric measurements (including height, weight, body mass index (BMI), waist circumference, hip circumference, and right wrist circumference), and blood pressure. The baseline questionnaires will be filled out right after patients are diagnosed with osteoporosis and then osteoporotic patients will be followed up regularly on a yearly basis. In the follow-up visit, variables that may have changed over time are updated. The main outcomes include registration of fall, fracture, hospitalization, medication adherence, and death. An online web-based user-friendly software is also developed for data collection. Data analysis will be conducted with the collaboration of data-mining experts and epidemiologists at the end of each follow-up., Conclusion: The Iran Osteoporosis Registry will be a valuable source of information regarding osteoporosis outcomes (i.e. fractures, hospitalizations, adherence, and death at the national level), and its results will be very beneficial and practical for policy makers in the field of musculoskeletal diseases., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. 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.)

In this study, the activity concentrations of 40 K, 232 Th, and 226 Ra radionuclides were estimated in imported milk powder samples from 40 brands available in local markets in Erbil Governorate, Iraq. The measurements were performed using High Purity Germanium (HPGe) detector. The results indicated that the average activity concentrations of 40 K, 232 Th, and 226 Ra were 241, 0.476, and 1.23 Bq kg -1 , respectively, and comparisons were made based on the typical consumption characteristics of powdered milk by Kurdistan residents. In all investigated age groups (2-17 years), the average annual effective doses were below the ICRP-recommended limit of 1 mSv y -1 for public exposure. Radiological hazard parameters were determined based on the measured radioactivity concentrations. The relation between all the determined activities of natural radionuclides and radiological parameters was examined using multivariate statistical analysis techniques such as histograms, descriptive statistics, and Pearson correlation analyses. The cancer risk in all samples was lower than the allowable value of (2.5 × 10 -3 ), while the ingestion dose in two samples was higher than the worldwide acceptable value of (0.29) mSv y -1 ., 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.)

CIC encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC's interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, as well as novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and an in vivo mouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines, predominantly at 3' and 5' untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CIC's functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CIC's potential roles in cancer. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts.

Purpose: There is plenty of evidence on the interventions that can improve outcomes of diabetes. Thus, there is an urgent need to innovate and provide cost-effective ways to optimize the best care for diabetes. The aim was to examine the components of diabetes courses to extract training virtual modules for training primary health care professionals (PHCPs) (i.e. general practitioners, nurses and nutritionists)., Methods: In this scoping review, a systematic approach based on the Arksey and O'Malley method was used. In order to develop the modules for diabetes courses, search strategy was developed using main keywords. Also, databases including PubMed, Web of Science, Scopus, CINAHL, ERIC and Embase, and Google search engine were searched up to April 10th 2021. Two researchers independently screened the retrieved courses. After removing duplicates, and according to the eligibility criteria, the components of each retrieved course were extracted., Results: Diabetes training courses have been selected to examine their components to extract training modules. Initially, we found 120 courses related to the training of PHCPs. All information about 44 courses were available online. The researchers reviewed the courses according to tool approved by panel of experts, inclusion criteria, and purpose of the study. Thus, we first extracted 23 eligible programs and 15 final programs were considered for extracting the modules. According to the tool developed by the panel of experts, we extracted 9 virtual modules for diabetes courses including principles, prevention or delay, management, complications, education, special conditions, information technology, referral system of diabetes for training PHCPs., Conclusion: Education is an important part of diabetes and needs of PHCPs should be addressed in educational programs in the future. The design of the diabetes training course based on extracted modules in this research for the training of PHCPs can help in this field., Competing Interests: Conflict of interestsThe Authors declare that there is no conflict of interests., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. 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.)

In this research, the radioactivity caused by natural radionuclides ( 40  K, 232 Th, and 226 Ra) was evaluated in infant milk consumed in Erbil, Iraq. The measurements were performed using an HPGe gamma-ray spectrometer. The variation of activity concentrations in milk samples was (99.56-256.9 Bq kg -1 ) for 40  K, (BDL-0.53 Bq kg -1 ) for 232 Th, and (0.27-5.59 Bq kg -1 ) for 226 Ra, as determined by the results. The radiological parameters of E ing , D org , and ELCR were calculated and compared to international standards. The correlation between computed radiological hazard parameters and natural radionuclides was analyzed statistically using Pearson's correlation. Overall, the results indicate that infant milk consumption in Erbil is radiologically safe and that consumers of these brands of milk are unlikely to be directly exposed to radiological health risks., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The current study assesses the collapse sensitivity classes of loess soils using gene expression programming (GEP) and ordinal logistic regression (OLR). The crucial variable to forecast the possible development of loess caves in the Golestan Province (northeast of Iran) is the collapse sensitivity factor (Is). A database of 62 records, including the mechanical and physical characteristics of soils, was used. Oedometer tests were used to estimate the parameters of the collapse coefficient, the time needed for 90% settlement (T90%), and collapse sensitivity. The database includes 10 inputs (grain size, porosity, initial water content, precipitation, climatic data, liquid limit, calcium carbonate content, vegetation, and degree of soil saturation) and one output (collapse sensitivity classes). This is a complicated approach due to the complexity of setting up and performing such kinds of tests in the laboratory. The likelihood of soil classification ranks as severe, moderately severe, moderate, and small sensitivity was inspected using OLR and GEP. This study demonstrated that the OLR approach could effectively differentiate among more than 70% of distinct groups. Furthermore, experimental data reported from Semnan, Sarakhs, and Mashhad also attests to the accuracy of the OLR model. The sensitivity analysis indicated that silt fraction imparts the maximum effect on the collapse sensitivity classes. The trial-and-error method was used to determine the configurations of the GEP model prior to developing an ideal model. The performance of the GEP model to estimate the collapse sensitivity categories in a trustworthy, strong, and useful way is well documented by comparison between the results of the GEP and the experimental findings, which are affordable., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Megacities recently are experiencing a shortage of green spaces basically due to the rapid growth of urbanization and increasing demand for different building types. Consideration of sustainable urban development is essential since the expansion of city facilities should be in line with social, economic, and environmental aspects. In this regard, green roof technology has been recommended as an effective solution for the growth of green spaces per capita and improving sustainability means of urban developments due to its diverse advantages. This study thus aimed at prioritizing sustainability indicators and relative sub-criteria of adopting green roof technology for residential and governmental buildings in the city of Mashhad, Iran, which has a dry climate. For this purpose, thirteen sub-criteria, which are extracted from the existing literature, are classified into three main sustainability indicators (environmental, economic, and social). Also, the best-worth method (BWM) as a multi-criteria decision-making technique was implemented to prioritize indicators and sub-criteria by analyzing the expert's opinion. The results indicated that respective economic and environmental indicators attract the highest priority in residential and governmental buildings. Additionally, the most important sub-criteria in environmental, economic, and social groups are air quality, roof longevity, and public health in both building types, respectively. However, when all criteria were considered, the respective highest priorities belong to roof longevity and air quality in residential and governmental buildings, while biodiversity conservation is the least important one in both building types. The results of this research can be beneficial in other cities with similar economic and climate conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Caffeine and ethanol are among the most widely available and commonly consumed psychoactive substances. Both interact with adenosine receptor-mediated signaling which regulates numerous neurological processes including sleep and waking behaviors. In mammals, caffeine is an adenosine receptor antagonist and thus acts as a stimulant. Conversely, ethanol is a sedative because it promotes GABAergic neurotransmission, inhibits glutamatergic neurotransmission, and increases the amount of adenosine in the brain. Despite seemingly overlapping interactions, not much is known about the effect of caffeine on ethanol-induced sedation in Drosophila . In this study, using Drosophila melanogaster as a model, we show that caffeine supplementation in food delays the onset of ethanol-induced sedation in males and females of different strains. The resistance to sedation reverses upon caffeine withdrawal. Heterozygous adenosine receptor mutant flies are resistant to sedation. These findings suggest that caffeine and adenosine receptors modulate the sedative effects of ethanol in Drosophila .

In a population of 1156 men aged ≥ 60 years, opioid drug use was reported by 4.1% (n = 47) of participants. Among opioids, opium was the most prevalent consuming drug (83%). Adjusting for potential confounders, opioid consumption showed a positive association with osteoporosis., Purpose: Limited evidence suggest a relationship between opioid consumption and osteoporosis. This study aims to investigate the possible association of osteoporosis and drug use among older adult men of Bushehr, Iran., Methods: In this study, 1156 men aged ≥ 60 years of Bushehr Elderly Health (BEH) were included. Bone density and trabecular bone score (TBS) were measured using dual-energy X-ray absorptiometry. Total osteoporosis was noted based on osteoporosis at either site of the lumbar spine, femoral neck, and total hip densitometry. Drug use was defined as a self-reported current use of opioid drugs, either regular (daily) use or irregular consumption. Multivariable modified Poisson regression analysis was used for investigating the association of opioids and osteoporosis, reporting the adjusted prevalence ratio (APR) with 95% confidence interval (CI). The association between drug use and TBS was evaluated using a linear regression model., Results: Opioid drug use was reported by 4.1% (n = 47) of participants. Among drug users, opium was the most prevalent consuming drug (83%). In all, 38.3% of drug users and 22.4% of non-users had osteoporosis (p-value = 0.011). Multivariable analysis showed that adjusting by age, education, smoking, alcohol consumption, body mass index, diabetes, and physical activity, a positive and significant association was detected between opioid drug use and the likelihood of osteoporosis (APR: 1.46, 95%CI: 1.02-2.10). Considering the potential confounders, the results also showed a negative association between drug consumption and TBS (β: - 0.027, 95%CI: - 0.053, - 0.001)., Conclusion: Opioid drug use has a positive association with osteoporosis in elderly men, independent of other conventional risk factors. Elderly drug users might be at a higher risk for osteoporotic fractures, given the effect of substance use on cognition. So, osteoporosis among drug users would be of importance, especially in countries where opium consumption is prevalent., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: Hypertension is one of the most important risk factors for premature mortality and morbidity in Iran. The objective of the Iranian blood pressure (BP) measurement campaign was to identify individuals with raised blood pressure and providing appropriate care and increase the awareness among the public and policymakers of the importance of tackling hypertension., Methods: The campaign was conducted in two phases. The first (communication) phase started on May 17th (International Hypertension Day). The second phase started on June 8th, 2019, and lasted up to July 7th during which, blood pressures were measured. The target population was Iranians aged ≥ 30 years. Participants voluntarily referred to health houses in rural and health posts and comprehensive health centers in urban areas in the setting of the Primary Health Care network. Additionally, over 13,700 temporary stations were set up in highly visited places in urban areas. Volunteer healthcare staff interviewed the participants, measured their BP, and provided them with lifestyle advice and knowledge of the risks and consequences of high blood pressure. They referred participants to physicians in case their BP was high. Participants immediately received a text message containing the relevant advice based on their measured BP and their past history., Results: Blood pressure was measured for a total of 26,678,394 participants in the campaign. A total of 13,722,148 participants (51.4%) were female. The mean age was 46 ± 14.1 years. Among total participants, 15,012,693 adults (56.3%) with no past history of hypertension had normal BP, 7,959,288 participants had BP in the prehypertension range (29.8%), and finally, 3,706,413 participants (13.9%) had either past medical history of hypertension, used medications, or had high BP measured in the campaign., Conclusion: The campaign was feasible with the objective to increase the awareness among the public and policymakers of the importance of tackling hypertension in Iran., Competing Interests: Competing interestsAll authors have organizational affiliation with the subdivisions of the Ministry of Health and Medical Education of Iran., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2022. Springer Nature or its licensor 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.)

Background: This paper presents the protocol of the 4 th round of Iranian Multi-center Osteoporosis Study (IMOS), a national survey with the primary objective of estimating the prevalence of osteoporosis and sarcopenia and their risk factors in a representative sample of urban and rural populations., Methods: The target population of the survey is all individuals ≥ 50 years in Iran. A multi-stage random sampling method has been used in the study. We stratified the 31 provinces of the country into 5 strata based on the distribution of their potential risk factors for osteoporosis and randomly selected one or two provinces from each stratum. Then, we invited 2530 people aged ≥ 50 years recruited in the 8 th National Survey of None Communicable Diseases (NCD) Risk Factors (STEPs-2021) in the selected provinces to participate in IMOS. Body composition measurements including bone mineral density, muscle mass, and fat mass are measured through Dual-energy X-ray Absorptiometry (DXA) method using HOLOGIC (Discovery and Horizon) devices; and Trabecular Bone Score (TBS) is measured on the DXA scans using iNsight software. Anthropometric measurement and physical examinations are made by a trained nurses and other required information are collected through face-to-face interviews made by trained nurses. Laboratory measurements are made in a central lab. The prevalence of osteoporosis and sarcopenia will be estimated after applying sampling design, non-response, and post-stratification weights to the data., Discussion: IMOS will provide valuable information on the prevalence and determinants of osteoporosis and sarcopenia at the national level, and the results can be used in evaluating health system interventions and policymaking in the field of musculoskeletal diseases., (© 2022. The Author(s).)

Background: Health status and perception can be assessed by general or disease-specific questionnaires, and disease specific questionnaires are more specific than general questionnaires. Considering the importance of breast health perception (BHP) in women's lives and the lack of any pertinent questionnaires, we performed this study to develop a valid and reliable short BHP questionnaire (BHPQ); and then used it to assess the participants' BHP., Methods: We first designed and developed the instrument and then measured its inter-rater agreement (IRA), content validity including content validity index (I-CVI) and scale content validity index (S-CVI), and reliability (through internal consistency and test-retest). We then evaluated the BHP of eligible women with normal breasts and benign breast disorders who attended our breast clinic., Results: The IRA index (78.6%) showed the optimal relevance and clarity of the questionnaire. The content validity was acceptable; with S-CVIs of 87.35 and 84.42 for clarity and relevance, respectively. The internal reliability was high (Cronbach's alpha = 0.93). Three questions were eliminated for internal consistency (intraclass correlation coefficient < 0.7) but the rest of the questions showed good and excellent reliability. In the next step, BHP in the 350 eligible participants showed an overall score of 43.89 ± 9.09., Conclusion: This study introduces a valid and reliable 11-item BHPQ. We propose its use in various circumstances throughout breast cancer screening, diagnosis, and treatment; and in the assessment of BHP in various physiologic and reproductive situations., (© 2022. The Author(s).)

Purpose: Our study examined whether T2DM and glucocorticoids treatment affect bone quality and quantity that are measured by Bone Mineral Density (BMD) and Trabecular Bone Score (TBS)., Materials & Methods: Participants in this study were 2294 women and men aged over 60 years who participated in stage II of the Bushehr Elderly Health (BEH) program. Patients with T2DM and those who received glucocorticoids were included. BMD was detected using the DXA method and the TBS of L1-L4 was evaluated by TBS iNsight® software. To evaluate the correlation between TBS and BMD levels with diabetes and taking corticosteroids sex-specific multivariable linear regression models were appplied., Results: TBS and BMD were not significantly different in those who had received glucocorticoids versus those who did not.T2DM revealed a significant association with both BMD and TBS in men (beta = 0.12, p < 0.001 and beta = 0.063, p = 0.03, respectively). BMD values were significantly higher in diabetic women (beta = 0.073, p < 0.01). BMI had a significant association with both TBS and BMD but in an opposite direction, in women and men (BMD: beta = -0.22, -0.24, and regarding TBS: beta = 0.37, 0.25, all p-values < 0.001)., Conclusion: Our findings showed that T2DM had major effects on BMD in both men and women. However, T2DM only affects TBS in men. Furthermore, neither BMD nor TBS were affected by GC intake in men or women.Based on the variable importance of covariates, BMI was the most influential factor on both BMD and TBS, although in opposite directions, in both sexes., Competing Interests: Conflict of InterestNone., (© Springer Nature Switzerland AG 2022.)

Quantum state tomography is a process for estimating an unknown quantum state; which is innately probabilistic. The exponential growth of unknown parameters to be estimated is a fundamental difficulty in realizing quantum state tomography for higher dimensions. Iterative optimization algorithms like self-guided quantum tomography have been effective in robust and accurate ascertaining a quantum state even with exponential growth in Hilbert space. We propose a faster convergent simultaneous perturbation stochastic approximation algorithm which is more practical in a resource-deprived situation for determining the underlying quantum states by incorporating the Barzilai-Borwein two-point step size gradient method with minimal loss of accuracy., (© 2022. The Author(s).)

Background: Discharge education practices vary among institutions and lack a standardized approach for newly diagnosed pediatric oncology patients and their parents., Objective: The purpose of this American Nurses Credentialing Center-supported pediatric multisite trial was to determine the feasibility and effectiveness of 2 nurse-led Parent Education Discharge Support Strategies (PEDSS) for families with a child who is newly diagnosed with cancer., Interventions/methods: A cluster randomized clinical trial design assigned 16 Magnet-designated sites to a symptom management PEDSS intervention or parent support and coping PEDSS intervention. Outcome measures evaluated at baseline, 1, and 2 months after diagnosis include symptom experiences, parent perceptions of care, unplanned service utilization, and parent evaluation of the PEDSS interventions., Results: There were 283 newly diagnosed children and their parent participating in this study. Linear mixed models revealed pain differed over time by the intervention; children in the symptom management group had a greater decrease in pain. Greater nausea and appetite disturbances were experienced by older children in both groups. Fatigue and sleep disturbance showed a significant decrease over time in both groups. The symptom management group reported significantly greater satisfaction with the PEDSS intervention., Conclusions: This study is among the first to examine the effects of 2 different early-discharge planning strategies for families of a newly diagnosed child with cancer. The evidence supports a standardized discharge education strategy that can be successfully implemented across institutions., Implications for Practice: Nurses play a major role in the educational preparation and discharge of newly diagnosed pediatric cancer patients and their families., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Introduction: Obesity and osteoporosis are health problems with high impact on the morbidity and mortality rate. While the association between BMI and bone density is known, the combined effects of obesity and metabolic components on bone health have not yet been revealed. The objectives of this study were to determine the association between bone health and different phenotypes of obesity in an elderly population., Methods: This cross-sectional study was conducted on the data collected in the Bushehr Elderly Health Program (BEHP). The participants were classified in four groups based on the metabolic phenotypes of obesity (metabolic healthy obese (MHO), metabolic non-healthy non-obese (MNHNO), metabolic non-healthy obese (MNHO), and metabolic healthy non-obese (MHNO)). The association between osteoporosis and TBS and the metabolic phenotypes of obesity were assessed using multiple variable logistic regression models., Results: Totally, 2378 people (1227 women) were considered for analyses. The prevalence of MHNO, MHO, MNHNO, and MNHO were 902 (39.9%), 138 (6.1%), 758 (33.5%), and 464 (20.5%), respectively. In the multivariate logistic regression models, those with MHO (OR 0.22; 95% CI 0.12-0.36), MNHNO (OR 0.52; 95% CI 0.4-0.66), and MNHO phenotypes (OR 0.22; 95% CI 0.16-0.3) had a significantly lower risk of osteoporosis. Likewise, those having MHO (OR 2.38; 95% CI 1.51-3.76), MNHNO (OR 1.49; 95% CI 1.11-2), and MNHO (OR 2.50; 95% CI 1.82-3.42) phenotypes were found to had higher risk of low bone quality as confirmed by TBS., Conclusions: The obese subjects have lower bone quality, regardless of their obesity phenotype.

In a large population-based study of Iran, the age-standardized prevalence of osteoporosis was 24.6% in men and 62.7% in women aged ≥ 60 years. Osteoporosis was negatively associated with body mass index in both sexes, and with diabetes in men and hypertriglyceridemia in women., Purpose: Population aging has made osteoporosis and osteoporotic fractures an important health problem, especially in developing countries. This study aimed to explore the prevalence of osteoporosis and associated factors among the elderly population of the south-west of Iran., Methods: Baseline data of the second stage of the Bushehr Elderly Health program was used. Spinal, total hip, or femoral neck osteoporosis was described as a BMD that lies 2.5 standard deviations or more, below the average values of a young healthy adult in the lumbar spine, total hip, or femoral neck, respectively. Osteoporosis at either site was defined as total osteoporosis. Age-standardized prevalence of osteoporosis was estimated. We used the modified Poisson regression with a robust variance estimator to identify the factors related to osteoporosis, adjusting for potential confounders., Results: Overall, 2425 individuals (1166 men) aged over 60 years were included. In all, total osteoporosis was detected in 1006 (41.5%) of the participants. Using the reference value derived from Caucasian women aged 20-29 years, the age-standardized prevalence of total osteoporosis was 24.6 (95% CI: 21.9-27.3) in men, and 62.7 (95% CI: 60.0-65.4) in women. In men, osteoporosis was positively associated with age, smoking, history of fracture, and history of renal/liver diseases and negatively associated with body mass index (BMI) and diabetes. BMI, hypertriglyceridemia, and education were negatively correlated with osteoporosis in women, while years after menopause and history of fracture increased the likelihood of osteoporosis, significantly., Conclusion: Results support the high prevalence of osteoporosis and osteopenia in the elderly population. Considering the importance of severe complications, especially fractures, comprehensive interventions should be expanded.

In this Letter, we experimentally demonstrate an unamplified analog RoF distribution of 60 GHz 5G signals. The system entails the heterodyning of two optical tones from an externally injected gain switched laser (EI-GSL) based optical frequency comb to generate a millimeter wave (mmW) signal. A fixed frequency separation and a high level of phase correlation, between the EI-GSL comb lines, results in the generation of a high-quality signal. An active demultiplexer is used to filter and amplify two comb tones, thus alleviating the need for an external optical amplifier to boost the low power comb tones. Furthermore, the same demultiplexer is also used to modulate one of the tones with a 64-QAM UF-OFDM signal. Such an approach enables the remote generation of a mmW downlink data signal as well as an unmodulated RF carrier that could be used to downconvert the mmW signals to an intermediate frequency. Using the abovementioned scheme, we demonstrate the distribution of the downlink signal over 25 km of fiber, achieving a BER of 2.4 e -3 (below the HD-FEC limit of 3.8 e -3) and only a 0.5 dB penalty at the FEC limit in comparison to the BtB case.

Competing Interests: Conflict of interestThere is no conflict of interest.

Context: Road traffic injuries is estimated to be the ninth leading cause of death across all age groups globally. People in need of trauma care, after a road crash, are most likely to survive if they receive definitive care within the first hour (Golden hour) after the crash. Essential prehospital care includes prompt communication, treatment, and transport of injured people to formal healthcare facilities., Aims: To assess the availability and utilization pattern of existing facilities for post-crash emergency care in Aligarh., Settings and Design: The present study was undertaken on two National highways- NH-91 and NH-93 and the connecting bypass roads of Aligarh district of Uttar Pradesh., Subjects and Methods: All the individuals who met road traffic accident (RTA) between the earmarked areas from 1 st October, 2018 to 30 th September, 2019 and reported for treatment (either on their own or brought by relatives, passersby, ambulance or police) to the selected hospitals were included in the study., Statistical Analysis Used: Data presented in the form of frequency tables and percentages., Results: Out of 665 patients interviewed during the study period, 556 (83.61%) patients were males and 109 (16.39%) were females with M: F ratio been 5.10:1. Among the first responders, 448 (67.36%) were lay persons and 42 (6.31%) were police personnel. 261 (39.25%) of patients received help within 10-30 min of RTA. Use of toll-free no. was limited to 265 (39.84%) patients. Ambulance was the mode of transport in 155 (23.30%) of RTA cases. 589 (88.58%) of patients reported to Government hospitals., Conclusions: Post-crash emergency care is in nascent stage in Aligarh district of Uttar Pradesh. Toll free numbers and ambulances are available but proper utilization and quality of care is lacking. Lay person is the most important personnel in improving the post-crash care., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Purpose: Smoking has been linked with osteoporosis, but further evidence is required, especially concerning the effects of different types of tobacco smoking. We sought to examine the association between smoking and bone health in a large cohort of elderly Iranians., Methods: The data from 2377 participants aged >60 years of Bushehr Elderly Health (BEH) program were used. Regardless of the type of smoking, participants were initially classified as non-smokers, ex-smokers and current smokers. Current smokers were also categorized based on the smoking type (pure cigarette, pure hookah and both). Dual-energy X-ray absorptiometry was used to evaluate bone density as well as Trabecular Bone Score (TBS). T-score ≤ -2.5 in either of the femoral neck, total hip or spinal sites was applied to determine the osteoporosis. The association of smoking and osteoporosis was assessed using multivariable modified Poisson regression model and reported as adjusted prevalence ratios (APR). The linear regression model was used to assess the association between smoking and TBS, adjusting for potential factors., Results: A total of 2377 (1225 women) were enrolled [mean age: 69.3 (±6.4) years], among which 1054 (44.3%) participants were nonsmokers. In all, 496 (20.9%) participants were current smokers. Multivariable regression analysis revealed no significant association between smoking (either current or past) and osteoporosis in women. In men, current smoking was negatively associated with osteoporosis (APR: 1.51, 95%CI: 1.16-1.96). Among current users, cigarette smoking was associated with osteoporosis (APR: 1.57, 95%CI: 1.20-2.03); however, we could not detect a significant association between current smoking of hookah and osteoporosis. In men, a significant association was also detected between current cigarette smoking and TBS (coefficient: -0.03, 95%CI: -0.01, -0.04)., Conclusion: Current cigarette smoking is associated with both the quantity and quality of bone mass in elderly men. Although we could not detect a significant association between hookah and osteoporosis in men, considering the prevalence of hookah smoking in the middle eastern countries, further studies are needed to determine the effect of hookah smoking on bone health., Competing Interests: Conflict of interestThere is no conflict of interest., (© Springer Nature Switzerland AG 2020.)

Proper function of cell signaling pathways is dependent upon regulated membrane trafficking events that lead to the endocytosis, recycling, and degradation of cell surface receptors. The endosomal complexes required for transport (ESCRT) genes play a critical role in the sorting of ubiquitinated cell surface proteins. CHMP2B Intron5 , a truncated form of a human ESCRT-III protein, was discovered in a Danish family afflicted by a hereditary form of frontotemporal dementia (FTD). Although the mechanism by which the CHMP2B mutation in this family causes FTD is unknown, the resulting protein has been shown to disrupt normal endosomal-lysosomal pathway function and leads to aberrant regulation of signaling pathways. Here we have misexpressed CHMP2B Intron5 in the developing Drosophila external sensory (ES) organ lineage and demonstrate that it is capable of altering cell fates. Each of the cell fate transformations seen is compatible with an increase in Notch signaling. Furthermore, this interpretation is supported by evidence that expression of CHMP2B Intron5 in the notum environment is capable of raising the levels of Notch signaling. As such, these results add to a growing body of evidence that CHMP2B Intron5 can act rapidly to disrupt normal cellular function via the misregulation of critical cell surface receptor function., (© 2019 Wiley Periodicals, Inc.)

Mutations in CHMP2B, an ESCRT-III (endosomal sorting complexes required for transport) component, are associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Neurodegenerative disorders including FTD are also associated with a disruption in circadian rhythms, but the mechanism underlying this defect is not well understood. Here, we ectopically expressed the human CHMP2B variant associated with FTD (CHMP2B Intron5 ) in flies using the GMR -GAL4 driver ( GMR >CHMP2B Intron5 ) and analyzed their circadian rhythms at behavioral, cellular, and biochemical level. In GMR >CHMP2B Intron5 flies, we observed disrupted eclosion rhythms, shortened free-running circadian locomotor period, and reduced levels of timeless ( tim ) mRNA-a circadian pacemaker gene. We also observed that the GMR -GAL4 driver, primarily known for its expression in the retina, drives expression in a subset of tim expressing neurons in the optic lobe of the brain. The patterning of these GMR - and tim -positive neurons in the optic lobe, which appears distinct from the putative clusters of circadian pacemaker neurons in the fly brain, was disrupted in GMR >CHMP2B Intron5 flies. These results demonstrate that CHMP2B Intron5 can disrupt the normal function of the circadian clock in Drosophila ., Competing Interests: The authors declare no conflict of interest., (© 2019 The Authors.)

Microglia and macrophages are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are differences in their representation and activity in the prognostically-favorable isocitrate dehydrogenase (IDH)-mutated compared to -wild type GBMs is unknown. Studies on human specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often present at lower grades, receiving treatments prior to dedifferentiation that can drastically alter microglia and macrophage phenotypes. We were able to obtain large samples of four previously untreated IDH-mutant GBM. Using flow cytometry, immunofluorescence techniques with automated segmentation protocols that quantify at the individual-cell level, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated microglia and macrophages (GAMMs) in IDH-mutant and -wild type GBMs. We found there are significantly fewer GAMM in IDH-mutant GBMs, but they are more pro-inflammatory, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates that more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. Interrogation of scRNA-seq databases demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wild type GBM. Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wild type GBMs. Our findings highlight biological disparities in the innate immune microenvironment related to IDH prognosis that can be exploited for therapeutic purposes., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

In this study, we determined the activity concentrations of naturally occurring radioactive nuclides in plant crops and the corresponding soil collected from greenhouses and agricultural fields in Erbil city in the Iraqi Kurdistan Region by using a high purity germanium detector. The soil-to-plant crops transfer factors were determined for radioactive nuclides. The results showed that the activity concentration ranges for 226 Ra, 232 Th, and 40 K in agricultural soils were (11.94-18.24) Bq/kg, (8.80-12.36) Bq/kg and (247.65-338.26) Bq/kg, respectively. The activity concentrations ranges for 226 Ra, 232 Th, and 40 K in plant crops were (0.20-1.45) Bq/kg, (0.11-0.48) Bq/kg, and (68.07-1355.36) Bq/kg, respectively. The transfer factors from soil to plant crops for 226 Ra, 232 Th and 40 K were in the ranges of (0.011-0.087), (0.011-0.046), and (0.201-5.130), respectively. The annual effective doses from consuming plant crops were also estimated. The values obtained were comparable to the internationally recommended values., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Capicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic's function in the brain. We show that nuclear Cic expression is strongest in astrocytes and neurons but weaker in stem cells and oligodendroglial lineage cells. Using a new conditional Cic knockout mouse, we demonstrate that forebrain-specific Cic deletion increases proliferation and self-renewal of neural stem cells. Furthermore, Cic loss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage effects are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal, and tumorigenicity. Our results identify Cic as an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.

Aims: Death-associated protein kinase-1 (DAPK1) is a pro-apoptotic Ser/Thr kinase that participates in cell apoptosis and tumor suppression. DAPK1 is frequently lost in many different tumor types including breast cancer. The aim of this study was to evaluate the promoter methylation status of DAPK1 and a possible correlation with the expression of DAPK1 and standard clinicopathological features in invasive ductal breast carcinoma patients (IDC). Methods: Methylation Specific PCR (MSP) was carried out to investigate the promoter methylation status of DAPK1 from 128 breast cancer patients. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry (n=128) and western blotting (n=56). Results: We found significant difference in DAPK1 promoter methylation frequency among breast tumors when compared with the corresponding normal tissues. Hypermethylation of DAPK1 is significantly correlated with the loss of DAPK1 protein expression (P < .001, rs= -0.361). The loss of DAPK1 protein was significantly associated with estrogen receptor (ER) negativity (p= 0.003), triple negative breast cancer (TNB) (p= 0.024) and advanced tumor stages (P = 0.001). Moreover, age at diagnosis (p= 0.041), tumor stage (p= 0.034), ER negativity (p= 0.004) and TNB cancers (p=0.003) correlated significantly with the hypermethylation of the DAPK1 promoter. Coclusion: This study indicates that DAPK1 is methylated in IDC and promoter hypermethylation could be attributed to silencing of DAPK1 gene expression in breast cancer. Thus, we consider DAPK1 inactivation by promoter hypermethylation likely plays a role in the development and progression of breast cancer., (Creative Commons Attribution License)

We investigated effects of apterous mutation ap 56f on circadian locomotor activity, eclosion rhythms, and transcript levels of period and timeless in Drosophila . We investigated circadian locomotor activity and eclosion rhythms in ap 56f and wild-type flies, their F1 and F2 offspring, and wingless vestigial mutants and show that ap 56f disrupts circadian locomotor rhythms in a genetically recessive manner, that is not caused by the absence of wings. The ap blt strain also showed impaired circadian activity rhythms, providing independent evidence for a significant role of apterous in circadian locomotor rhythm expression. The ap 56f mutation did not disrupt a circadian eclosion rhythm or rhythmic expression of the period and timeless clock genes, indicating that apterous is not essential for circadian clock function, but is necessary for coupling locomotor activity to a circadian clock. Timeless transcription was reduced in ap 56f flies in 12:12 LD, suggesting that apterous may modulate core clock gene expression.

Microsporidia are eukaryotic, intracellular obligate parasites that widely involve many organisms including insects, fish, birds, and mammals. One of the genera of Microsporidia is Encephalitozoon , which contains several opportunistic pathogens. Since Encephalitozoon spp. are zoonotic and opportunistic pathogens, it is important to find their reservoir hosts; hence, the current study aimed at isolating and identifying Encephalitozoon spp. in the crows by the light microscopy observations and molecular methods. For this purpose, 36 samples were collected by the dropping method; however, due to the low volume of samples, the total samples were collected in a sterile stool container and the polymerase chain reaction (PCR) was performed to detect Encephalitozoon spp. Accordingly, 300-bp bands, specific to Encephalitozoon spp., were observed and by sequencing E. intestinalis was identified. Crows can be considered as the hosts of E. intestinalis ., Competing Interests: The authors declare that they have no competing interests.The sampling was done in the form of dropping out and there was no ethical issue.

DNA methylation catalyzed by DNA methyl transferase (MTase) is a significant epigenetic process for modulating gene expression. Abnormal levels of DNA MTase enzyme have been regarded as a cancer biomarker or a sign of bacterial diseases. We developed a novel colorimetric method to assay M.SssI MTase activity employing peroxidase-like activity of DNA template Ag/Pt NCs without using restriction enzymes. Based on inhibiting the peroxidase reaction that occurred in the TMB-H 2 O 2 system, in the presence of MTase, a highly sensitive and selective colorimetric biosensor was fabricated with a detection limit (LOD) of 0.05 U/mL and a linear range from 0.5 to 10 U/mL. The changes in absorption intensity were monitored to quantify the M.SssI activity. This strategy had a high selectivity over other proteins. Furthermore, it is also demonstrated that this method can be used for the evaluation and screening of inhibitors for DNA MTase.

Frontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in CHMP2B locus ( CHMP2B intron5 ), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-III), is associated with a rare hereditary subtype of FTD linked to chromosome 3 (FTD-3). ESCRT is involved in critical cellular processes such as multivesicular body (MVB) formation during endosomal⁻lysosomal pathway and autophagy. ESCRT mutants causes diverse physiological defects primarily due to accumulation of endosomes and defective MVBs resulting in misregulation of signaling pathways. Charged multivesicular body protein 2B (CHMP2B) is important for neuronal physiology which especially rely on precise regulation of protein homeostasis due to their post-mitotic status. Drosophila has proven to be an excellent model for charaterization of mechanistic underpinning of neurodegenerative disorders including FTD. In this review, current understanding of various FTD-related mutations is discussed with a focus on Drosophila models of CHMP2B intron5 -associated FTD., Competing Interests: The authors declare no conflict of interest.

DNA repair machinery preserves genomic integrity, which is frequently challenged through endogenous and exogenous toxic insults, and any sort of repair machinery malfunctioning ultimately manifests in the form of several types of terrible human diseases such as cancers (Hoeijmakers, Nature 411(6835): 366-374, 2001). Noncoding RNAs (ncRNAs) are crucial players of DNA repair machinery in a cell and play a vital role in maintaining genomic stability, which is essential for its survival and normal functioning thus preventing tumorigenesis. To preserve the integrity of the genome, cells initiate a specific cellular response, recognized as DNA damage response (DDR), which includes several distinct DNA repair pathways. These repair pathways permit normal cells to repair DNA damage or induce apoptosis and cell cycle arrest in case the damage is irreparable. Disruption of these pathways in cancer leads to an increase in genomic instability and mutagenesis. Recently, emerging evidence suggests that ncRNAs play a critical role in the regulation of DDR. There is an extensive crosstalk between ncRNAs and the canonical DDR signaling pathway. DDR-induced expression of ncRNAs can provide a regulatory mechanism to accurately control the expression of DNA damage responsive genes in a spatio-temporal manner. DNA damage alters expression of a variety of ncRNAs at multiple levels including transcriptional regulation, post-transcriptional regulation, and RNA degradation and vice versa, wherein ncRNAs can directly regulate cellular processes involved in DDR by altering expression of their targeting genes, with a particular emphasis on microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Relationship between the defects in the DDR and deregulation of related ncRNAs in human cancers is one of the established, which is growing stronger with the advent of high-throughput sequencing techniques such as next-generation sequencing. Understanding of the mechanisms that explain the association between ncRNAs and DDR/DNA repair pathways will definitely increase our understanding on human tumor biology and on different responses to diverse drugs. Different ncRNAs interact with distinct DDR components and are promising targets for improving the effects to overcome the resistance to conventional chemotherapeutic agents. In this chapter, we will focus the role of ncRNAs in the DNA damage, repair, and cancer.

MicroRNAs (miRNAs) are a large family of small, approximately 20-22 nucleotide, noncoding RNAs that regulate the expression of target genes, at the post-transcriptional level. miRNAs are involved in virtually diverse biological processes and play crucial roles in cellular processes, such as cell differentiation, proliferation, and apoptosis. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. It is possible that the diverse roles that miRNAs play, have potential to provide valuable information in a clinical setting, demonstrating the potential to act as both screening tools for the stratification of high-risk patients, while informing the treatment decision-making process. Increasing evidence suggests that some miRNAs may even provide assistance in the diagnosis of patients with breast cancer. In addition, miRNAs may themselves be considered therapeutic targets, with inhibition or reintroduction of a particular miRNA capable of inducing a response in-vivo. This chapter discusses the role of miRNAs as oncogenes and tumor suppressors in breast cancer development and metastasis . It focuses on miRNAs that have prognostic, diagnostic, or predictive potential in breast cancer as well as the possible challenges in the translation of such observations to the clinic.

There is increasing evidence in support of multidisciplinary approaches for management of chronic neck pain. Although presence of different team members is one of the strengths of these approaches, it can limit the access to these treatments. The main objective of this study is designing and investigating the efficacy of a concise rehabilitation program. Thirty-nine patients with sub-acute and chronic non-specific neck pain underwent an 8-week rehabilitation program. Baseline and 8 weeks' follow-up data regarding neck pain (visual analog scale, neck disability index and quality of life) were compared using paired T test. After eight weeks of study, pain and disability significantly decreased: -3.8 of 10 (95% CI: -4.6 to -3.0) (p-value < 0.001) for pain and -18.4 of 100 (95% CI: -23.7 to -13.2) (p-value < 0.001) for disability. Also, all SF-36 domain scales improved significantly. By using this concise rehabilitation approach, pain, disability, and quality of life improved significantly in patients with sub-acute and chronic non-specific neck pain., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Previous studies have shown atrophy of paravertebral lumbar muscles in patients with lumbar radicular pain and have proposed rehabilitative approaches based on these findings. However, changes in cervical paravertebral muscles in patients with cervical radicular pain are still unknown., Objective: The aim of this study was to compare the cross-sectional area (CSA) of the longus colli muscle (LCM) in patients with cervical radicular pain and healthy controls via ultrasound measurement., Study Design: Case-control study., Setting: Outpatients who came for treatment to the neurosurgery clinic., Participants: A total of 20 patients with more than 4 weeks of cervical radicular pain and 20 healthy matched (for body mass index, age, and gender) control subjects., Interventions: Ultrasound measurements., Main Outcome Measures: The CSA of the LCM at the level of C5-C6 was measured by ultrasound with the subject in supine position. Also, Neck Disability Index (NDI), and visual analogue scale (VAS) scores were reported by patients. An independent-sample t test was used for investigation of differences in CSA and other variables in both groups., Results: A total of 20 patients with cervical radicular pain with a mean age of 42.4 years (standard deviation [SD] = 7 years) and 20 healthy matched controls with mean age of 40.7 years (SD = 7 years) participated in the study. Patients with cervical radicular pain showed smaller CSA of the LCM bilaterally compared with controls (mean difference: 0.37 [SD = 0.15]; P < .001). In the patient group, there were no significant differences between the CSA of the LCM in the involved and noninvolved sides. No correlations between the CSA of the LCM and VAS, Neck Disability Index, symptom duration, gender, BMI, and age of the patients were found., Conclusions: This is the first study to show via ultrasound assessment that patients with cervical radicular pain had smaller bilateral CSA of the LCM in comparison with healthy controls. It is also not clear whether atrophy of the LCM in patients with cervical radicular pain is a consequence or a cause of the pain. Reduction in the stability of the neck due to atrophy of the LCM could make the cervical spine region susceptible to more injuries, which might be prevented by functional and strengthening exercises., Level of Evidence: III., (Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Charged multivesicular body protein 2B (CHMP2B) - a component of the endosomal complex required for transport-III (ESCRT-III) - is responsible for the vital membrane deformation functions in autophagy and endolysosomal trafficking. A dominant mutation in CHMP2B (CHMP2B Intron5 ) is associated with a subset of heritable frontotemporal dementia - frontotemporal dementia linked to chromosome 3 (FTD-3). ESCRT-III recruits Vps4, an AAA-ATPase that abscises the membrane during various cellular processes including autophagy and intraluminal vesicle formation. CHMP2B Intron5 results in a C-terminus truncation removing an important Vps4 binding site as well as eliminating the normal autoinhibitory resting state of CHMP2B. CHMP2B is expressed in most cell types but seems to be especially vital for proper neuronal function. CHMP2B Intron5 -mediated phenotypes include misregulation of transmembrane receptors, accumulation of multilamellar structures, abnormal lysosomal morphology, down regulation of a brain-specific micro RNA (miRNA-124), abnormal dendritic spine morphology, decrease in dendritic arborization, and cell death. Currently, transgenic-fly,-mouse, and -human cell lines are being used to better understand the diverse phenotypes and develop therapeutic approaches for the CHMP2B Intron5 -induced FTD-3. This article is part of a Special Issue entitled SI:Autophagy., (Copyright © 2016 Elsevier B.V. All rights reserved.)