Molecular evaluation of Ex3 VNTR polymorphism of the DRD4 gene in patients with autism spectrum disorder

Abstract Objective Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders that affect social and communication skills. They are characterized by severe communication and social skills disabilities and limited and repetitive activities and their prevalence appear to be steadily increasing. Genes involved in the dopamine pathway may play an important role in the development of autism and this study we evaluated the possible association between Ex3 VNTR polymorphism of the DRD4 gene and autism spectrum disorder in the Iranian population. Materials & Methods In this case-control study,97 children with autism and 103 healthy individuals were selected from the northwestern area of Iran as the case group and the control group, respectively. After genomic extraction from peripheral blood samples by the proteinase K method, the polymerase chain reaction (PCR) technique was used to determine the genotypes of polymorphism. The data then were coded and analyzed using SPSS22 software. Result The results of the study showed that the allele frequencies were different in the two groups and some of these differences were statistically significant. The most common allele in both the ASD and the control group was the 700 bp allele and its frequency was significantly different in the two groups, being more common in the ASD group. (p-value=0.0018). The other allele with a statistically different frequency was the 800 bp allele which was less frequent in the ASD group (p-value=0.0017). Conclusion These results suggest a potential association between Ex3 VNTR polymorphism of the DRD4 gene and autism spectrum disorder in the Iranian population and necessitate further studies evaluating the DRD4 gene

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors for heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials.

AIMS: We sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF). METHODS: We searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% confidence intervals (95% CIs) were pooled using a random-effects model. RESULTS: We included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%). CONCLUSION: The use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42022364223)

Assessment of prevalence and risk factors of isolated coronary artery ectasia: A 5-year double-center retrospective study in Yazd, Iran

Background: The prevalence of Coronary artery ectasia (CAE) varies from 0.‌3 to 5% in different countries. The prevalence of CAE has varied in different parts of the world and the study of risk factors can be effective in the process of diagnosis and treatment of patients, we reviewed patients who underwent coronary angiography for 5 years to determine the prevalence of isolated CAE and its associated risk factors. Methods: A retrospective analysis was conducted on 16600 patients who underwent coronary angiography at Shahid Sadoughi and Afshar hospitals between March 2015 to April 2020. Diagnosis and confirmation of CAE was defined as a vessel diameter greater than 1.5 times the normal diameter of the vessel, which must be confirmed by at least two cardiologists. Demographic variables, angiography and echocardiography reports were included in our final analysis. Results: Isolated CAE was diagnosed in 287 (1.7%) patients. After triple-vessel disease (53%), the left anterior descending artery (LAD) was the commonest affected vessel by ectasia 16% (46 cases). Diffuse isolated CAE was diagnosed in 52% of LAD, 76.6% of Right coronary artery (RCA), and 74.1% of left circumflex artery. A significant association was seen between the vessel involved and the nature of ectasia (p<0.001). Conclusion: In our study, the occurrence of isolated CAE was similar to other studies. This condition often affects all three major vessels of the coronary arteries, and is commonly categorized as type 1, which involves diffuse involvement of the arteries based on the Markis and Harikrishnan Classification

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Brain‐derived neurotrophic factor (BDNF) levels in panic disorder: A systematic review and meta‐analysis

Abstract Background The existing literature on the association between brain‐derived neurotrophic factor (BDNF) protein levels and panic disorder presents inconsistent findings. This systematic review and meta‐analysis aim to synthesize the available evidence and determine the overall effect of BDNF protein levels in individuals diagnosed with panic disorder. Methods A comprehensive literature search was conducted using electronic databases (PubMed, Embase, Scopus, PsycINFO, and Web of Science) from inception to April 21, 2023. The search strategy included relevant keywords and medical subject headings terms related to BDNF, panic disorder, and protein levels. A random‐effects model was used for the meta‐analysis, and subgroup analyses were performed to explore heterogeneity. Publication bias was assessed using funnel plots and statistical tests. Results A total of 12 studies met the inclusion criteria. The meta‐analysis demonstrated a significant decrease in BDNF protein levels in individuals with panic disorder (SMD = −.53, 95% CI: −1.02 to −.04, p < .001; I2: 92%). The results of subgroup and meta‐regression analyses were not statistically significant. No significant publication bias was observed based on the results of Egger's regression test (p‐value = .3550). Conclusion This systematic review and meta‐analysis provide evidence of lower BDNF protein levels in individuals diagnosed with panic disorder compared to healthy controls. The findings suggest a potential role for BDNF dysregulation in the pathophysiology of panic disorder. Further research is warranted to elucidate the underlying mechanisms and potential therapeutic implications

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar‐I disorder: A double‐blind, randomized, placebo‐controlled clinical trial

Abstract Introduction Treatment of mood and cognitive symptoms of patients with bipolar disorder is associated with many complications and is generally not associated with therapeutic satisfaction. In this clinical trial, we evaluated the effectiveness of spironolactone in controlling mood and cognitive symptoms, sleep quality, appetite, and body mass index in patients with bipolar disorder in manic episodes. Methods Sixty inpatients with bipolar disorder in manic episodes were treated with spironolactone/placebo in an 8‐week randomized, double‐blind, placebo‐controlled clinical trial. They were evaluated using the Young Mania Rating Scale (YMRS), mini‐mental state examination (MMSE), Pittsburgh sleep quality index, Simplified Nutritional Appetite Questionnaire, and body mass index in weeks 1, 4, and 8. Results For cognitive impairment (MMSE), there were significant interaction effects of group and time at week 8 (B = −1.60, SE = 0.69, t = −2.33, p = .021) such that individuals in the spironolactone group experienced more improvement in their cognitive performance. For manic symptoms (YMRS), there were no significant interaction effects of group and time at week 8 (B = −2.53, SE = 1.46, t = −1.73, p = .085). Conclusions Considering the promising findings in this clinical trial, further study of spironolactone as adjunctive therapy in bipolar disorder in manic episodes with larger sample sizes, multicenter settings, and longer follow‐ups are recommended

Ultrasound versus fluoroscopy as imaging guidance for percutaneous nephrolithotomy: A systematic review and meta-analysis.

ObjectivesTo determine whether the outcomes of ultrasound-guided percutaneous nephrolithotomy (UG-PCNL), an alternative to traditional fluoroscopy-guided percutaneous nephrolithotomy (FG-PCNL), are comparable.MethodsA systematic search of PubMed, Embase, and the Cochrane Library was carried out to discover investigations comparing UG-PCNL to FG-PCNL, and accordingly, a meta-analysis of those studies was performed. The primary outcomes included the stone-free rate (SFR), overall complications based on Clavien-Dindo classification, duration of surgery, duration of patients' hospitalization, and hemoglobin (Hb) drop during the surgery. All statistical analyses and visualizations were implemented utilizing R software.ResultsNineteen studies, including eight randomized clinical trials (RCTs) and eleven observational cohorts, comprising 3016 patients (1521 UG-PCNL patients) and comparing UG-PCNL with FG-PCNL met the inclusion criteria of the current study. Considering SFR, overall complications, duration of surgery, duration of hospitalization, and Hb drop, our meta-analysis revealed no statistically significant difference between UG-PCNL and FG-PCNL patients, with p-values of 0.29, 0.47, 0.98, 0.28, and 0.42, respectively. Significant differences were discovered between UG-PCNL and FG-PCNL patients in terms of the length of time they were exposed to radiation (p-valueConclusionUG-PCNL provides the advantage of requiring less radiation exposure while being just as efficient as FG-PCNL; thus, this study suggests prioritizing the use of UG-PCNL

Providing a Framework for Reforming Premium Rates of Vehicle Collision Coverage with Using Neural Networks Model (A Case Study of Asia Insurance Company)

Since vehicle collision coverage, unlike what it seems, is not very profitable for insurance companies and is moving towards making losses, this paper considered the adequacy of measures and rates used by insurance companies, and intended to optimize the methods by employing more scientific approaches. In order to do so, first, the factors affecting the risk of policy holders were identified and after comparing these factors with existing data in the database of surveyed company, the final factors were selected. Then, after preprocessing these data, prediction of the damage class and the quantity of policyholders’ potential damages were accomplished using neural networks model. So that, with using these results and considering their damage ratio, insurance companies could define optimized premium rates for their policies. The results showed that the offered model was able to predict the damage class and potential damages of policy holders respectively with 91 and 87 percent accuracy

Human T-cell lymphotropic virus type 1 (HTLV-1) proposed vaccines: a systematic review of preclinical and clinical studies

Abstract Background Numerous vaccination research experiments have been conducted on non-primate hosts to prevent or control HTLV-1 infection. Therefore, reviewing recent advancements for status assessment and strategic planning of future preventative actions to reduce HTLV-1 infection and its consequences would be essential. Methods MEDLINE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through March 27, 2022. All original articles focusing on developing an HTLV-1 vaccine candidate were included. Results A total of 47 studies were included. They used a variety of approaches to develop the HTLV-1 vaccine, including DNA-based, dendritic-cell-based, peptide/protein-based, and recombinant vaccinia virus approaches. The majority of the research that was included utilized Tax, Glycoprotein (GP), GAG, POL, REX, and HBZ as their main peptides in order to develop the vaccine. The immunization used in dendritic cell-based investigations, which were more recently published, was accomplished by an activated CD-8 T-cell response. Although there hasn't been much attention lately on this form of the vaccine, the initial attempts to develop an HTLV-1 immunization depended on recombinant vaccinia virus, and the majority of results seem positive and effective for this type of vaccine. Few studies were conducted on humans. Most of the studies were experimental studies using animal models. Adenovirus, Cytomegalovirus (CMV), vaccinia, baculovirus, hepatitis B, measles, and pox were the most commonly used vectors. Conclusions This systematic review reported recent progression in the development of HTLV-1 vaccines to identify candidates with the most promising preventive and therapeutic effects

The prevalence of sleep disturbance and its possible associated factors among iranian medical students: A cross-sectional study with a national meta-analysis

Background: The aim of this cross-sectional study was to investigate the prevalence of sleep disturbance and its possible associated factors among Iranian medical students. Additionally, a national meta-analysis was conducted to provide a comprehensive overview of sleep disturbance in this population. Methods: A sample of medical students from Guilan University of Medical Sciences, Iran was included in the study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep disturbance. Demographic and lifestyle factors, as well as academic performance, were collected through a self-administered questionnaire. The data collected from this study were combined with existing studies through a meta-analysis to estimate the overall prevalence of sleep disturbance among Iranian medical students using the random effects model. Results: A total of 249 medical students participated in the study. The prevalence of sleep disturbance among Guilan University of Medical Sciences medical students was found to be 71.1%. A significant difference was observed in total PSQI means regarding medical students’ residency (p < 0.001) and their duration of sleep in the last 24 h (p = 0.006). The national prevalence of sleep disturbances was 59% (95% CI: [51%–66%], I2 = 97%). Conclusion: Sleep disturbance is highly prevalent among Iranian medical students, with various factors contributing to its occurrence. The findings of this study highlight the need for interventions and strategies to improve sleep quality and overall well-being among this population. The national meta-analysis provides valuable insights into the overall burden of sleep disturbance among Iranian medical students and can serve as a reference for future studies and public health initiatives targeting this issue