Bayesian spatio-temporal modeling of hyperlipidemia risk in Iran; A repeated cross-sectional analysis

Background: The incidence of hyperlipidemia in Iran is on a consistent rise, potentially contributing significantly to increased susceptibility to cardiovascular diseases and other health complications linked to elevated blood lipid levels. This study employs hierarchical Bayesian model to assess the heightened lipid risk on a broader scale across Iran's provinces. Thise model play a pivotal role in spatial modeling, adeptly handling uncertainties arising from diverse spatial data sources. Methods: This study included individuals diagnosed with hyperlipidemia from all provinces of Iran in 2019. The primary focus of the investigation included essential variables such as the mean age, gender distribution, and the documented incidence of hyperlipidemia cases in each province. Population data, stratified by province, age group, and gender, were sourced from the Iranian Statistics Center database. Utilizing a direct approach, disease prevalence and expected case numbers were calculated. The analysis employed the Besag-York-Mollié (BYM) model, with parameter estimation executed through the Hamiltonian Monte Carlo method. Results: In this investigation, the prevalence and spatial distribution of hyperlipidemia were explored within a diverse population of 1,609,538 patients across various regions in Iran. The relative risk of hyperlipidemia surpassed 1 in 16% of Iranian provinces (posterior probability > 0.8), with a calculated 95% confidence interval of 0.304 to 0.879. The overall prevalence of hyperlipidemia was determined to be 0.815. Significant heterogeneity in hyperlipidemia was identified among different provinces, with Tehran exhibiting the highest relative risk (RR=1.701; 95% CrI: 1.69, 1.713). Notably, gender (RR=1.008; CI: 1.007, 1.009 for males and RR=1.005; CI: 1.003, 1.007 for females) and age were not found to have a statistically significant effect on the relative risk of the disease. Conclusions: In conclusion, this investigation employed hierarchical Bayesian models to evaluate the prevalence and spatial distribution of hyperlipidemia across the provinces of Iran. The analysis unveiled a significant escalation in the relative risk of hyperlipidemia in 16% of Iranian provinces, underscoring the spatial heterogeneity in disease prevalence. This study contributes invaluable insights into the spatial dynamics of hyperlipidemia in Iran, establishing a groundwork for the formulation of targeted public health strategies

Efficacy of nicorandil treatment for prevention of contrast-induced nephropathy in high-risk patients undergoing cardiac catheterization: A prospective randomized controlled trial

Background: Contrast-induced nephropathy (CIN) remains to be a potentially serious complication of radiographic procedures and is the third leading cause of the acute kidney injury (AKI) among hospitalized patients. This clinical trial was performed to assess the preventive effect of oral nicorandil on CIN in high-risk patients undergoing cardiac catheterization. Methods: In this prospective, randomized, controlled trial, 128 patients with at least two risk factors for CIN undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to either the nicorandil group or the control group. Patients in the nicorandil group (n = 64) received 10 mg nicorandil, daily from 30 min before and up to 3 days after procedure and intravenous hydration for 2 h before and 6 h after the procedure, whereas patients in the control group (n = 64) just received intravenous hydration. Serum creatinine (SCr) was measured before contrast exposure and at 72 h. CIN was defined as an increase of 25% in SCr or > 0.5 mg/dL 72 h after contrast administration. Results: Contrast-induced nephropathy occurred in 14 out of 64 (21.9%) patients in the control group and in 3 out of 64 (4.7%) patients in the nicorandil group. There was a significant difference in the incidence of CIN between the two groups at 72 h after administering the radiocontrast agent (p = 0.008). Moreover, there were significant differences between the two groups in SCr and estimated glomerular filtration rate 72 h after radiocontrast administration (p < 0.05). Conclusions: The findings revealed that oral nicorandil had substantial efficacy over hydration protocol for the development of CIN in high-risk patients undergoing cardiac catheterization.

VDR and CYP24A1 Expression Analysis in Iranian Relapsing-Remitting Multiple Sclerosis Patients

Objective: Multiple sclerosis (MS) is a common disease of the central nervous system. This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor. Materials and Methods: In this case-control study, the expression of genes encoding vitamin D receptor (VDR) and CYP24A1 in relapsing-remitting MS (RR-MS) patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients (HLA-DRB1*15-negative and responders to interferonbeta with a normal vitamin D level) and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction. Results: The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group (P=0.04). On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expanded disability status scale of Kurtzke (EDSS) and the expression level of either CYP24A1 or VDR. In addition, the expression level of CYP24A1 or VDR was not correlated with the duration of the disease. Conclusion: Up-regulation of VDR is likely to happen in RR-MS patients in the Iranian population. We did not observe a gene expression-phenotype correlation for CYP24A1 which may be due to limited statistical power as a result of the small sample size. Although the individuals taking part in this study had normal levels of vitamin D, the increase in VDR expression levels may perhaps be a response to a defect in vitamin D processing. Another possibility is that despite an increase in VDR expression level, factors such as micro-RNAs may result in their deactivation while an increase in VDR expression level can be seen as a compensatory response. Of course, further studies are required to identify the mechanism of action of vitamin D by analyzing genes involved in its signaling pathway, particularly VDR and CYP24A1

Dysregulation of NF-κB-Associated LncRNAs in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a long-standing neurodevelopmental condition with prominent effects on social behavior of affected children. This disorder has been linked with neuroinflammatory responses. NF-κB has been shown to affect these responses in the orbitofrontal cortex of patients with ASD, thus being implicated in the pathogenesis of ASD. We measured expression of some NF-κB-associated lncRNAs and mRNAs (DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, NKILA, ATG5 and CEBPA) in the peripheral blood of ASD kids vs. healthy children. Expression quantities of ADINR, ANRIL, DILC, NKILA and CHAST were meaningfully higher in ASD cases compared with healthy kids (Posterior Beta = 1.402, P value < 0.0001; Posterior Beta = 2.959, P value < 0.0001; Posterior Beta = 0.882, P value = 0.012; Posterior Beta = 1.461, P value < 0.0001; Posterior Beta = 0.541, P value = 0.043, respectively). The Bonferroni corrected P values for these lncRNAs remained significant except for CHAST and DILC. Expression levels of other genes were not considerably different between cases and controls. Expressions of ATG5, DICER-AS1 and DILC were correlated with age of ASD patients (P < 0.0001). Among ASD cases, the most robust correlation has been detected between ADINR and NKILA (r = 0.87, P < 0.0001). Expression of none of genes has been correlated with age of healthy children. Among this group of children, expression levels of ADINR and CHAST were robustly correlated (r = 0.83, P < 0.0001). ANRIL had the greatest AUC value (AUC = 0.857), thus the best diagnostic power among the assessed genes. NKILA ranked the second position in this regard (AUC = 0.757). Thus, NF-κB-associated lncRNAs might partake in the pathogenesis of ASD

Expression Analysis of Ermin and Listerin E3 Ubiquitin Protein Ligase 1 Genes in the Periphery of Patients with Schizophrenia

Schizophrenia (SCZ) is a severe mental disorder with an unknown etiology. Recent researches indicate that correct myelination and translational regulation play a role in the pathogeny of SCZ. This study evaluated the expression pattern of Ermin (ERMN) and Listerin E3 ubiquitin protein ligase 1 (LTN1) genes, which play a role in myelination and ribosome quality control, respectively. The expression of the ERMN and LTN1 genes in the peripheral blood (PB) of 50 SCZ patients (male/female: 22/28, age (mean ± standard deviation (SD)): 35.9 ± 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean ± SD): 34.7 ± 5.4) were assessed using quantitative polymerase chain reaction. Additionally, we used a bioinformatics approach based on microarray dataset analysis to examine the expression of these two genes in olfactory epithelium (OE) specimens. The expression of ERMN demonstrated no significant differences in PB samples among SCZ patients and healthy controls (adjusted P-value = 0.101). The expression of LTN1 was significantly higher in PB samples obtained from female patients compared with sex-matched controls (posterior beta = 1.734, adjusted P-value < 0.0001). Significant correlations were found between expression of the mentioned genes in PB samples both among SCZ patients and among healthy controls (r = 0.485, P < 0.001 and r = 0.516, P < 0.001, respectively). According to our in silico findings, the ERMN expression levels in OE samples of SCZ were statistically higher than those in controls (log2FC = 1.93, adj.P.Val = 9.66E-15). On the contrary, LTN1 expression levels in OE samples were statistically lower in SCZ cases versus controls (log2FC = − 0.77, adj.P.Val = 2.14E-06). Besides, a significant correlation was found between the expression of the mentioned genes in OE samples (r = − 0.60, P < 0.001). In conclusion, the present study is the first evidence to highlight the expression of the ERMN and LTN1 genes in the periphery of SCZ patients. Our findings may provide light on the SCZ’s pathogeny

Analysis of ROQUIN, Tristetraprolin (TTP), and BDNF/miR-16/TTP regulatory axis in late onset Alzheimer’s disease

Alzheimer’s disease (AD) is a heterogeneous degenerative disorder of the brain that is on the rise worldwide. One of the critical processes that might be disturbed in AD is gene expression regulation. Tristetraprolin (TTP) and RC3H1 gene (ROQUIN) are two RNA-binding proteins (RBPs) that target AU-rich elements (AREs) and constitutive decay elements (CDEs), respectively. TTP and ROQUIN, members of the CCCH zinc-finger protein family, have been demonstrated to fine-tune numerous inflammatory factors. In addition, miR-16 has distinct characteristics and may influence the target mRNA through the ARE site. Interestingly, BDNF mRNA has ARE sites in the 3’ untranslated region (UTR) and can be targeted by regulatory factors, such as TTP and miR-16 on MRE sequences, forming BDNF/miR-16/TTP regulatory axis. A number of two microarray datasets were downloaded, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD and corresponding controls. R software was used to identify BDNF, TTP, ROQUIN, and miR-16 expression levels in temporal cortex (TC) tissue datasets. Q-PCR was also used to evaluate the expression of these regulatory factors and the expression of BDNF in the blood of 50 patients with AD and 50 controls. Bioinformatic evaluation showed that TTP and miR-16 overexpression might act as post-transcriptional regulatory factors to control BDNF expression in AD in TC samples. Instead, this expression pattern was not found in peripheral blood samples from patients with AD compared to normal controls. ROQUIN expression was increased in the peripheral blood of patients with AD. Hsa-miR-16-5p levels did not show significant differences in peripheral blood samples. Finally, it was shown that TTP and BDNF, based on evaluating the receiver operating characteristic (ROC), effectively identify patients with AD from healthy controls. This study could provide a new perspective on the molecular regulatory processes associated with AD pathogenic mechanisms linked to the BDNF growth factor, although further research is needed on the possible roles of these factors in AD

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study

Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients \u3e 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P\u3c0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. Conclusion: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p &lt; 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS &lt; 5) ischemic stroke (p &lt; 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p &lt; 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic

Prevalence of Academic Burnout and Its Related Factors among Medical Student in Qom, Iran

Background and Objectives: Academic burnout negatively affects students and those around them in terms of subjective well-being, psychology, and physiology. This study aims to determine academic burnout and its related factors in students of Qom University of Medical Sciences. Methods: This cross-sectional study was conducted on 274 medical students studying in second and higher semesters in Qom University of Medical Sciences, 2015. The samples were selected using stratified sampling method. The Breso et al.'s Academic Burnout Inventory and demographic characteristics questionnaire were completed by students. Data were analyzed using Pearson correlation coefficient and multivariate analysis of variance at significance level of 0.05. Results: The mean age of the subjects was 21.9&plusmn;3.7 years and the mean score of academic burnout was 1.73&plusmn;0.64 (range:0-4). According to the results of multivariate analysis of variance, there were statically significant relationships between academic burnout and variables of residence status and interest in the academic discipline (p<0.05). In addition, the results of Pearson correlation coefficient were indicative of an inverse statistical correlation between academic burnout status and the variables of age (r=-166, p<0.0001) and educational status (r=-0.242, p<0.0001). Conclusion: Considering the significant relationship between grade point average and interest in academic discipline with all subscales, planning to create a positive attitude towards academic discipline in students can be a protective factor against academic burnout as well as improvement of educational status