Search

Abstract Background Diabetes is a strong risk factor for cardiovascular disease (CVD).The relative role of various lipid measures in determining CVD risk in diabetic patients is still a subject of debate. We aimed to compare performance of different lipid measures as predictors of CVD using discrimination and fitting characteristics in individuals with and without diabetes mellitus from a Middle East Caucasian population. Methods The study population consisted of 1021 diabetic (men = 413, women = 608) and 5310 non-diabetic (men = 2317, women = 2993) subjects, aged ≥ 30 years, free of CVD at baseline. The adjusted hazard ratios (HRs) for CVD were calculated for a 1 standard deviation (SD) change in total cholesterol (TC), log-transformed triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using Cox proportional regression analysis. Incident CVD was ascertained over a median of 8.6 years of follow-up. Results A total of 189 (men = 91, women = 98) and 263(men = 169, women = 94) CVD events occurred, in diabetic and non-diabetic population, respectively. The risk factor adjusted HRs to predict CVD, except for HDL-C, TG and TG/HDL-C, were significant for all lipid measures in diabetic males and were 1.39, 1.45, 1.36 and 1.16 for TC, LDL-C, non- HDL-C and TC/HDL-C respectively. In diabetic women, using multivariate analysis, only TC/HDL-C had significant risk [adjusted HR1.31(1.10-1.57)].Among non-diabetic men, all lipid measures, except for TG, were independent predictors for CVD however; a 1 SD increase in HDL-C significantly decreased the risk of CVD [adjusted HR 0.83(0.70-0.97)].In non-diabetic women, TC, LDL-C, non-HDL-C and TG were independent predictors. There was no difference in the discriminatory power of different lipid measures to predict incident CVD in the risk factor adjusted models, in either sex of diabetic and non-diabetic population. Conclusion Our data according to important test performance characteristics provided evidence based support for WHO recommendation that along with other CVD risk factors serum TC vs. LDL-C, non-HDL-C and TC/HDL-C is a reasonable lipid measure to predict incident CVD among diabetic men. Importantly, HDL-C did not have a protective effect for incident CVD among diabetic population; given that the HDL-C had a protective effect only among non- diabetic men.

Abstract Background The Middle East is estimated to have the largest increase in prevalence of diabetes by 2030; yet there is lack of published data on the incidence of Type 2 diabetes in this region. This study aimed to estimate Type 2 diabetes incidence and its associated risk factors in an Iranian urban population. Methods Among 3307 non-diabetics ≥ 20 years (mean age 42 ± 13 years, 42% males), glucose tolerance test was performed at baseline in 1999–2001 and at two consecutive phases in 2001–2005 and 2005–2008. Diabetes and glucose tolerance status were defined according to the ADA 1997 criteria. Logistic regression was used to determine the independent variables associated with incident diabetes and their odds ratios (OR). Results After median follow-up of 6 years, 237 new cases of diabetes were ascertained corresponding to an age and sex standardized cumulative incidence of 6.4% (95%CI: 5.6–7.2) and incidence rate of 10.6 (9.2–12.1) per 1000 person years. Besides classical diabetes risk factors, female sex and low education level significantly increased risk of diabetes in age adjusted models. In full model, the independent predictors were age [OR, 95%CI: 1.2 (1.1–1.3)], family history of diabetes [1.8 (1.3–2.5)], body mass index ≥ 30 kg/m2 [2.3 (1.5–3.6)], abdominal obesity [1.9 (1.4–2.6)], high triglyceride [1.4 (1.1–1.9)], Isolated impaired fasting glucose (IFG) [7.4 (3.6–15.0)], Isolated impaired glucose tolerance (IGT) [5.9 (4.2–8.4)] and combined IFG and IGT [42.2 (23.8–74.9)]. Conclusion More than 1% of the Iranian urban population older than 20 years develops Type 2 diabetes each year. Combination of IFG and IGT was the strongest predictor of incident diabetes among the modifiable risk factors.

Abstract Background To investigate the association of Aspartate aminotransferase (AST), Alanin aminotranferase (ALT) and Gamma glutamyl transferase (GGT) with incident type 2 diabetes. Methods In a nested case-control study, AST, ALT, GGT as well as classic diabetes risk factors, insulin and C-reactive protein (CRP) were measured in 133 non-diabetic subjects at baseline of which 68 were cases and 65 were controls. Incident diabetes was defined by the WHO 1999 criteria. Conditional logistic regression was used to calculate the odds ratio (OR) of incident diabetes associated with different hepatic markers. We used factor analysis for clustering of classic diabetes risk factors. Results In Univariate analysis both ALT and GGT were associated with diabetes with ORs of 3.07(1.21–7.79) and 2.91(1.29–6.53) respectively. After adjustment for CRP and insulin, ALT and GGT were still predictive of incident diabetes. When the model was further adjusted for anthropometric, blood pressure and metabolic factors, only ALT was independently associated with diabetes [OR = 3.18 (1.02–9.86)]. No difference was found between the area under the receiver operating characteristic curves of the models with and without ALT (0.820 and 0.802 respectively, P = 0.4) Conclusion ALT is associated with incident type 2 diabetes independent of classic risk factors. However, its addition to the classic risk factors does not improve the prediction of diabetes.

Abstract Background To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years. Methods The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes. Results The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values 2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4). Conclusion In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.

Ever since the discovery of the brain's orexin/hypocretin system, most research was directed toward unveiling its contribution to the normal functioning of individuals. The investigation of reward-seeking behaviors then gained a lot of attention once the distribution of orexinergic neurons was revealed. Here, we discuss findings on the involvement of orexins in social interaction, a natural reward type. While some studies have succeeded in defining the relationship between orexin and social interaction, the controversy regarding its nature (direct or inverse relation) raises questions about what aspects have been overlooked until now. Upon examining the literature, we identified a research gap concerning conditions influencing the impact of orexins on social behavior expression. In this review, we introduce a number of factors (e.g., stress, orexin's source) that must be considered while studying the role of orexins in social interaction. Furthermore, we refer to published research to investigate the stage at which orexins affect social interaction and we highlight the nucleus accumbens (NAc) shell's role in social interaction and other rewarding behaviors. Finally, the underlying orexin molecular pathway influencing social motivation in particular illnesses is proposed. We conclude that orexin's impact on social interaction is multifactorial and depends on specific conditions available at a time.

Noscapine, a phthalide isoquinoline alkaloid isolated from the opium poppy, alongside cotarnine, a tetrahydroisoquinoline (THIQ) scaffold produced by the oxidative degradation of noscapine, has exhibited antitumor activities against several types of cancer. Although derivatization with amino acids is regarded as a promising strategy to improve chemotherapeutics' anticancer properties, amino acid conjugates of noscapine and cotarnine have been the least investigated. In the present study, 20 amino acid conjugated derivatives of noscapine and cotarnine at the 6-position were synthesized and evaluated for anticancer activity in both in vitro and in vivo conditions. Analysis of the antiproliferative activity against 4T1 mammary carcinoma tumor cells showed that compounds 6h (noscapine-phenylalanine), 6i (noscapine-tryptophan), and 10i (cotarnine-tryptophan) with IC 50 values of 11.2, 16.3, and 54.5 μM, respectively, were found to be far more potent than noscapine (IC 50 = 215.5 μM) and cotarnine (IC 50 = 575.3 μM) and were consequently opted for further characterization. Annexin V and propidium iodide staining followed by flow cytometry demonstrated improved apoptotic activity of compounds 6h , 6i , and 10i compared to those of noscapine and cotarnine. In a murine model of 4T1 mammary carcinoma, noscapine-tryptophan inhibited tumor growth more effectively than noscapine and the other amino acid conjugates without adverse effects. Moreover, molecular docking studies conducted on tubulin as the intracellular target of noscapine suggested a good correlation with experimental observations. Based on these results, noscapine-tryptophan could be a promising candidate for further preclinical investigations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Because of the association of lumbar lordosis with some clinical conditions such as low back pain, the chiropractic field has emphasized the significance of evaluating the lumbar lordotic status, by measuring Cobb's angle, regarded as the radiological gold standard, for the assessment of lumbar lordosis, on lateral radiographs. However, research has shown that this technique has some considerable drawbacks, mostly in terms of low accuracy and high variability between clinicians when compared with other radiological modalities. The main objective was to compare the diagnostic accuracy of newly established radiological measurements with one of Cobb's angle methods, for the characterization of lumbar lordosis status in a sample of Lebanese patients aged 15 and above., Material and Methods: This retrospective single-center study consisted of measuring Cobb's L1-S1 and Cobb's L1-L5 angles, along with the novel established measurements which are the derivative and the normalized surface area, on 134 lateral radiographs of the lumbar spine of Lebanese patients aged fifteen years old and above, gotten from the Radiology department at Zahra'a's Hospital in Beirut, performed by two observers using MATLAB. Inter-rater agreement was assessed by calculating the Intra-class correlation coefficients. Spearman correlation was analyzed between both Cobb's angle methods and with the derivative and normalized area respectively. 54 patients of the sample were diagnosed by two radiologists, according to their LL status. ROC curve analysis was performed to compare the diagnostic accuracy of the four techniques used. Data were analyzed with IBM SPSS Statistics 23.0 (NY, USA); P  < 0.05 was considered statistically significant., Results: According to the ROC curve analysis the new methods, which are the derivative and the normalized surface area, displayed lower diagnostic accuracy (AUC derivative  = 0.818 and 0.677, AUC surface area  = 0.796 and 0.828) than Cobb's L1-L5 (AUC L1-L5  = 0.924 and 0.929 values) and L1-S1 (AUC L1-S1  = 0.971 and 0.955) angles, in the characterization of hypo and hyperlordotic patients, respectively, in our Lebanese sample consisting of patients aged 15 and above, because of their lower area under the curve's values compared to the traditional Cobb's techniques. The Cobb's L1-S1 has shown to have the highest diagnostic accuracy among the four methods to characterize normal patients from hypo and hyperlordotic ones, by referring to its highest area under the curve's values. However, the sensitivity of Cobb's L1-L5 angle in characterizing hyperlordotic patients was similar to the one of the normalized surface area with a value of 100%.Conclusion: among the four modalities, the new methods didn't show a better diagnostic accuracy compared to the traditional modalities. Cobb's L1-S1 displayed the highest diagnostic accuracy despite its drawbacks. Further prospective studies are needed to validate the cut-offs obtained for Cobb's L1-S1 angle in our sample., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Background/objective: Multiple Sclerosis is a common demyelinating disease of the central nervous system. Several studies suggested a link between vitamin D deficiency and multiple sclerosis disease activity, which can be evaluated by magnetic resonance imaging. Thereby, the main objective of the following scoping review is to summarize the magnetic resonance imaging findings assessing the probable effects of vitamin D on MS disease activity., Methodology: PRISMA checklist for systematic reviews and meta-analyses was employed to structure this review. Literature was searched for observational and clinical studies tackling the given matter using several search engines including PubMed, CORE, and Embase. Data was extracted in a systematic manner, and the articles meeting the inclusion criteria were quality-assessed by Jadad scale for randomized clinical trials (RCTs) and Newcastle-Ottawa scale for observational studies., Results: A total of 35 articles were included. Twenty-one (60%) studies noted a statistically significant association between vitamin D and Multiple Sclerosis MRI-detected disease activity. MRI-detected features involved lower contrast-enhancing T1 lesions, lower hyperintense T2 lesions, and a decrease in lesions volume. On the other hand, 40% (14 articles) of the articles did not detect any significant effect of vitamin D on Multiple Sclerosis disease activity. Due to the heterogeneity of the studies involved, meta-analysis was not employed in the given review., Discussion/conclusion: There was an abundance in the number of research studies investigating the relationship between vitamin D and Multiple Sclerosis while highlighting the significant role of MRI in assessing the activity of the disease. Numerous studies found that higher serum vitamin D levels are associated with decreased new active cortical and subcortical lesions and lower lesions volume. These findings highlight the importance of imaging modalities in the various aspects of neurological diseases and encourage further research to focus on the preventive effects of vitamin D on MS patients., (© 2023 The Authors.)

Background: Aggression towards nurses in the workplace arises from various reasons, reportedly increasing during the COVID-19 pandemic. Where aggression can be maintained by spiritual well-being, as it is said that spirituality is a coping skill and psychological well-being maintainer-but there is little known, especially during the pandemic. Thus, this study explored the effect of spirituality on aggression among the nurses working in the COVID-19 wards., Methods: This cross-sectional data from 200 nurses involved in the COVID-19 patient treatment were collected using a random sampling method from four hospitals in East Mazandaran province, Iran. Responses were collected based on socio-demographics, Buss-Perry Aggression Questionnaire, and Paloutzian & Ellison Spiritual Well-being Scale. T-test, ANOVA, Pearson correlation coefficient, and multiple linear regression were applied for data analysis., Results: The mean age of nurses was 31.49±6.88 (range: 21-48) years. Nurses working in the COVID-19 wards have a mean score of spiritual health of 67.21±12.84 (out of 120), whereas 51.77±10.96 (out of 116) was for aggression. The results showed a significant negative weak correlation between aggression and spiritual health (r = -.285, p<0.01). As per regression analysis, spiritual health [β = -.264], age [β = -.374], and working experience [β = 4.156] were the significant factors associated with aggression (p<0.05)., Conclusions: It is evident that nurses who consider spirituality in their life actions are in a state of reduced negative emotions, such as aggression. Thus, policymakers and managers of the healthcare settings are suggested to promote spirituality among the nurses through spiritual care education, providing the ground for promoting spirituality and a positive attitude towards it., Competing Interests: The authors of the research work do not have any conflict of interest., (Copyright: © 2022 Harati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dysarthria is a common and persisting sequela to stroke. It can have a negative influence on psychological wellbeing, and quality of life. This systematic review aimed to describe and identify the neuroanatomical regions associated with non-progressive dysarthria following stroke., Methods: A systematic search of PubMed, Ovid Medline, CINAHL, Cochrane, Scopus, and ScienceDirect was conducted to identify all relevant articles published in peer-reviewed journals up to December 2021. Following data extraction, the National Institutes of Health (NIH) quality assessment tools were used to evaluate the methodological quality of the included studies., Results: Out of 2186 papers found in the literature related to dysarthria post-stroke, 24 met the inclusion criteria. Eligible articles assessed 1150 post-stroke subjects. Out of them, 420 subjects had dysarthria from isolated lesions. Regarding dysarthric subjects with ischemic strokes, 153 sustained supratentorial infarctions, while 267 had infratentorial infarctions. The majority had pontine infarctions (n = 142), followed by infarctions in the corona radiata (n = 104), and the cerebellum (n = 64)., Conclusion: This systematic review is the first step toward establishing a neuroanatomical model of dysarthria throughout the whole brain. Our findings have many implications for clinical practice and provide a framework for implementing guidelines for early detection and management of dysarthria post-stroke., (© 2022. The Author(s).)

Background: Data on the efficacy and safety of COVID-19 vaccines in patients with malignancy are immature. In this paper, we assessed the literature involving the use of COVID-19 vaccines in cancer patients and reported the seroconversion rates as the main outcome and severity of COVID-19 infection and side effects following COVID-19 vaccination as the secondary outcomes., Methods: A systematic review with meta-analysis was performed. Searches were conducted in electronic websites, databases, and journals, including Scopus, PubMed, Embase, and Web of Science from January 01, 2019, to November 30, 2021. Studies reporting data on the safety and efficacy of COVID vaccine in cancer patients using any human samples were included. The risk of bias was assessed using the NEWCASTLE-OTTAWA scale in the included studies., Results: A total of 724 articles were identified from databases, out of which 201 articles were duplicates and were discarded. Subsequently, 454 articles were excluded through initial screening of the titles and abstracts. Moreover, 41 studies did not report the precise seroconversion rate either based on the type of cancer or after injection of a second dose of COVID vaccine. Finally, 28 articles met all the inclusion criteria and were included in this systematic review. The overall seroconversion rates after receiving a second dose of COVID-19 vaccine, based on type of cancer were 88% (95% CI, 81%-92%) and 70% (95% CI, 60%-79%) in patients with solid tumors and hematologic malignancies, respectively., Conclusion: Overall, we conclude that vaccination against COVID-19 in patients with active malignancies using activated and inactivated vaccines is a safe and tolerable procedure that is also accompanied by a high efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Javadinia, Alizadeh, Mojadadi, Nikbakht, Dashti, Joudi, Harati, Welsh, Farahmand and Attarian.)

Background: Glioma is the most frequent primary brain tumor and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors. This study aimed to investigate the immunohistochemical expression level of cannabinoid type-1 receptors (CB1R) in human glioma samples and evaluate its clinicopathologic significance., Materials and Methods: We analyzed the expression of CB1R in 61 paraffin-embedded glioma and 4 normal brain tissues using automated immunohistochemical assay. CB1R expression was categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and phosphorylated extracellular signal-related kinase (p-ERK) expression levels and the clinicopathologic features of glioma., Results: Our results showed that CB1R immunopositivity was seen in 59 of 61 cases (96.7%). CB1R was down-expressed in glioma compared to normal brain tissues. However, CB1R expression was not correlated with clinicopathological parameters except for p-ERK., Conclusion: Our findings indicate the down-expression of CB1R in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas should be further tested regardless of the clinicopathological findings to provide a therapeutic advantage in glioma patients., (Copyright © 2022 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Background: Non-progressive dysarthria is an acquired motor speech disorder resulting from neurological diseases such as stroke and traumatic brain injury. The evidence base for the assessment of non-progressive dysarthria remains limited with professional practices relying mainly on therapists' clinical experience. Limited information on the assessment practices of Lebanese speech and language therapists (SLTs) is available. Such information is crucial for the development of adequate therapy services for clients with non-progressive dysarthria. This study aims to explore the assessment practices and attitudes of Lebanese SLTs working with adults with non-progressive dysarthria and to investigate their adherence to the framework of the World Health Organization's International Classification of Functioning, Disability and Health (ICF)., Methods: A cross-sectional study was conducted in Lebanon between March and May 2021. Data was collected through an online survey that included information on socio-demographic characteristics, practices, and attitudes of SLTs who assess adults with non-progressive dysarthria., Results: A total of 50 Lebanese SLTs responded to the survey. The majority of SLTs (78%) assessed clients with non-progressive dysarthria across all ICF domains. SLTs reported dissatisfaction with the available assessment tools (64%) and reliance on informal tools (84%). In addition, 68% of the SLTs suggested the crucial need for the development of Arabic formal assessments that can quantitatively evaluate dysarthria and determine severity. The survey also showed that the respondents demonstrated a preference for the use of impairment-based tools., Conclusion: It can be concluded that the assessment practices of Lebanese SLTs, generally, follow the international trend and the recommended professional guidelines. Further research initiatives should be held to develop Arabic formal assessment tools for non-progressive dysarthria., (© 2021. The Author(s).)

Background: Chemokines are proinflammatory cytokines that play key roles in development of cardiovascular diseases (CVD). Chemokine-induced recruitment of peripheral leucocytes to tissues is a crucial step in the CVD progression. CC chemokines ligand 5, 2 (CCL5 and CCL2), have been characterized as emerging inflammatory biomarkers of atherosclerotic CVD. The aim of this study was to find out whether genetic polymorphisms of CCL5 -403 G>A (rs2107538) and CCL2 -927 G>C, (rs3760396) were associated with the risk of CVD., Methods: In this case-control study, 500 Iranian individuals including 250 CVD patients and 250 healthy subjects as the control group participated in 2017. Genotyping of CCL5 -403 G>A and CCL2 -927 G>C polymorphisms were executed using Tetra-ARMS PCR method., Results: At genotypic level both CCL5 -403 G>A and CCL2 -927 G>C polymorphisms were not associated with the risk of CVD ( P >0.05), even after adjustment by age, sex, race, and history of hypertension, DM and smoking. However, the CCL2 -927 C allele was associated with an increased risk of CVD (OR=1.42, P =0.050) with a higher prevalence in CVD patient than in controls (17% vs. 12%). Moreover, the haplotype analysis revealed that CCL5/CCL2 haplotype (G/C) was a risk factor for CVD (OR=2.13, P =0.001), and that carriers of this haplotype were at 2.13-fold higher risk of CVD than subjects with G/G haplotype., Conclusion: CCL2 -927 C variant and CCL5/CCL2 haplotype (G/C) were associated with susceptibility to CVD, and were risk factors for CVD in our population but more studies with large sample size are recommended., (Copyright © 2021 Mohtavinejad et al. Published by Tehran University of Medical Sciences.)

Urmia Lake is the largest lake in the Middle East which has greatly decreased in recent years. It has had a great impact on the environmental properties of areas around the lake. This study aimed to identify the relationship among dust storms in the eastern part of Urmia Lake and the surrounding vegetation due to the annual and long-term variability of this water zone during the statistical period 1999-2019. Normalized difference water index (NDWI), normalized difference vegetation index (NDVI), Aerosol Optical Depth (AOD), and Dust Storm Index (DSI) were used due to trend and correlation analysis models and T-student analysis. The study results found that, first, the decreasing trend of Urmia Lake, directly and significantly, has led to an increase in dust concentration (AOD) in the lake's eastern part. On the other hand, changes in the water level of Lake Urmia have led to a general decreasing trend in vegetation in the region which led to an increase in the frequency of DSI in the region. The model developed showed that changes in the water zone of Urmia Lake as a very powerful driver leads to an increase in the intensity and frequency of dust storms in the eastern part of the lake and intensifies the dust conditions in the region. The synergistic resultant of these two drivers was maximized in years when both lake area and vegetation were at a minimum at the same time (2011-2016). The estimated scenario of this model is that if the decreasing trend of Urmia Lake intensifies in the study area, more frequent and severe dust storms will occur in the region.

Background: Gliomas are a group of diseases arising from intracranial neoplastic tissues that produce a wide spectrum of clinicopathological features and morphological changes. Key questions that intrigue neuro-oncology researchers include defining novel oncophenotypic signatures relevant to diagnosing such tumors and predicting prognoses among patients. One of the key regulators of the cellular actin dynamics is adenylyl cyclase-associated protein 2 (CAP2), a protein that has been studied before in the milieu of cancer and shown to be associated with tumor progression; yet, its expression levels in the context of gliomas have not been assessed. Hence, we were interested in investigating CAP2 expression in gliomas and evaluating its clinicopathological and prognostic significance., Materials and Methods: CAP2 expression at the protein level was analyzed in 47 human paraffin-embedded gliomas and normal brain tissues by automated immunohistochemical analysis. Statistical analysis was also performed to assess CAP2 expression level in normal and tumor tissues, and to evaluate its clinicopathological and prognostic significance., Results: Our results revealed high expression of CAP2 protein in tumors of gliomas compared to normal tissues and normal areas adjacent to tumors. High expression of CAP2 was also associated with advanced tumor grades among gliomas. Kaplan-Meier analysis revealed that high CAP2 expression was associated with poor prognosis of patients with glioma (P < 0.05). In Cox regression analysis, CAP2 expression was indicated as an independent prognostic factor for overall survival (hazard ratio (HR) = 1.843, 95% confidence interval (CI), 1.252-2.714; P < 0.005)., Conclusion: CAP2 is overexpressed in glioma and it is proposed as a potential prognostic biomarker for patients with gliomas. CAP2 expression level may serve as a promising target for diagnosis and treatment of glioma., (© 2020 The Author(s).)

Aims/hypothesis: Several epidemiological studies have shown an increased risk of atrial fibrillation in individuals with type 2 diabetes or milder forms of dysglycaemia. We aimed to assess whether this relation is causal using a Mendelian randomisation approach., Methods: Two-sample Mendelian randomisation was used to obtain estimates of the influence of type 2 diabetes, fasting blood glucose (FBG), and HbA 1c on the risk of atrial fibrillation. Instrumental variables were constructed using available summary statistics from meta-analyses of genome-wide association studies (GWAS) for type 2 diabetes and associated phenotypes. Pleiotropic SNPs were excluded from the analyses. The most recent GWAS meta-analysis summary statistics for atrial fibrillation, which included over 1 million individuals (approximately 60,000 individuals with atrial fibrillation) was used for outcome analysis., Results: Neither type 2 diabetes (OR 1.01 [95% CI 0.98, 1.03]; p = 0.37), nor FBG (OR 0.95 [95% CI 0.82, 1.09] per mmol/l; p = 0.49) or HbA 1c (OR 1.01 [95% CI, 0.85, 1.17] per mmol/mol [%]; p = 0.88) were associated with atrial fibrillation in Mendelian randomisation analyses. We had >80% statistical power to detect ORs of 1.08, 1.06 and 1.09 or larger for type 2 diabetes, FBG and HbA 1c , respectively, for associations with atrial fibrillation., Conclusions/interpretation: This Mendelian randomisation analysis does not support a causal role of clinical significance between genetically programmed type 2 diabetes, FBG or HbA 1c and development of atrial fibrillation. These data suggest that drug treatment to reduce dysglycaemia is unlikely to be an effective strategy for atrial fibrillation prevention., Data Availability: The datasets analysed during the current study are available from the following repository: Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al (2018) GWAS summary statistics for AF (N=60,620 AF cases and 970,216 controls). Center for Statistical Genetics: http://csg.sph.umich.edu/willer/public/afib2018/nielsen-thorolfsdottir-willer-NG2018-AFib-gwas-summary-statistics.tbl.gz.

CLN3 disease is a neurodevelopmental disease leading to early visual failure, motor decline, and death. CLN3 pathogenesis has been linked to dysregulation of ceramide, a key intracellular messenger impacting various biological functions. Ceramide is upregulated in brains of CLN3 patients and activates apoptosis. Ceramide levels over the lifespan of WT and Cln3 Δ ex7/8 mice were measured using the DGK assay. Ceramide subspecies were determined by LC-MS. Ceramide synthesis enzymes and pre- and post-synaptic mRNA expression was measured in Cln3 Δ ex7/8 and normal mouse brains. Neuronal cell death was established by PARP cleavage and Caspases 3/6/9 and cytochrome C mRNA expression in Cln3 Δ ex7/8 and normal mouse brains. In WT mouse, a ceramide peak was noted at 3 weeks of age. The absence of this peak in Cln3 Δ ex7/8 mice might be related to early disease pathogenesis. Increase of ceramide in Cln3 Δ ex7/8 mouse brain at 24 weeks of age precedes neuronal apoptosis. The correlation between serum and brain ceramide in WT mice, and dysregulation of ceramide in serum and brain of Cln3 Δ ex7/8 mice, and the significant increase in ceramide in Cln3 Δ ex7/8 mouse brains and sera argue for use of easily accessible serum ceramide levels to track response to novel therapies in human CLN3 disease.

Context: We summarized findings from Tehran lipid and glucose study (TLGS) about different aspects of type 2 diabetes (T2D) over the span of nearly 2 decades., Evidence Acquisition: A review was undertaken to retrieve papers related to all aspects of T2D from the earliest date available up to January 30, 2018., Results: An annual crude incidence rate of 10 per 1000 person-years of follow-up was found for T2D in adult participants. Overall incidence rate of pre-diabetes/T2D was 36.3 per 1000 person-years or about 1% each year among youth. Diabetes was associated with increased risk of CVD [hazard ratio (HR): 1.86, 95% confidence interval (95% CI): 1.57 - 2.27] and mortality [HR: 2.56; 95% CI: 2.08 - 3.16] in the total population. Compared with non-diabetic men and women, their diabetic counterparts survived 1.4 and 0.7 years shorter, respectively, during 15 years of follow-up. Wrist circumference, hyperinsulinaemia, 25-hydroxy vitamin D and increase in alanin aminotranferase provided incremental prognostic information beyond the traditional risk factors for incident T2D in adults. Using decision tree algorithms, a number of high risk groups were found for incident T2D. A probability of 84% was found for incidence of T2D among a group of men with fasting plasma glucose (FPG) > 5.3 mmol/L and waist to height ratio (WHtR) > 0.56, and women with FPG > 5.2 mmol/L and WHtR > 0.56., Conclusions: Original TLGS studies have contributed greatly to clarify important evidence regarding the epidemiology and risk factors for T2D among Iranian population.

Diabetes prevalence and deaths attributable to diabetes continue to rise across globally. Diabetes Self-Management Education and Support (DSME/S) is a critical resource designed to help people with diabetes (PWD) successfully selfmanage their disease; however, its utilization is too low. In the Islamic Republic of Iran, there are currently limited structured educational programmes and no national standards for DSME/S protocol. In response to this, the GABRIC Diabetes Education Association (GDEA) has been developed as a school for diabetics, which has a comprehensive DSME/S programme for PWD with 18 distinct courses on 5 levels for 8 target groups. In addition, GABRIC has developed a database registry with more than 100 000 members throughout the country, of whom 95% are diabetic with a proportion of 82% Type 2 diabetes and 13% Type 1 diabetes. The success of the GABRIC school model results is yet to be investigated through study trials, and offers a fruitful line of research., (Copyright © World Health Organization (WHO) 2018. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: Hypothyroidism (HT) and hypoparathyroidism (HPT) are common endocrine complications in thalassemia major (TM) patients., Objectives: In the present study, we assessed the frequency of HT and HPT in a population of TM patients in Southeast of Iran., Methods: This cross sectional study was performed on 194 TM patients in Zabol, Sistan and Baluchestan Province, Iran, during February - July 2016. The demographic, clinical, and laboratory data were collected via interviews and history - taking. For hormone measurements, specific ELISA kits were used. Statistical analysis was performed in SPSS version 16., Results: A total of 103 (53.1%) and 91 (46.9%) females and males were recruited in this study, respectively. The mean age of the patients was 15 ± 7.5 years. HT and HPT showed overall frequencies of 8.2% (18/194) and 18% (35/194), respectively. Subclinical and overt HT were observed in 13 (6.7%) and 5 (2.6%) patients, respectively. There was no significant association between HT and age, while patients with HPT were significantly older than those without HPT (20.1 ± 5.8 vs. 13.9 ± 6.2 years; P < 0.001). HPT was significantly associated with the mean received blood per transfusion (P = 0.009), total transfused blood per year (P = 0.01), splenomegaly (P < 0.001), splenectomy (P < 0.001), hepatomegaly (P = 0.01), and chelation regimen (P < 0.001). The ferritin level was correlated with neither HT nor HPT. Also, no significant difference was observed between patients with or without HT or HPT regarding the cooccurrence of either diabetes or hepatitis C virus (HCV) infection. In the multivariate analysis, splenectomy remained an independent risk factor for HPT after correction for potential covariates (OR, 6.5; 95% CI, 1 - 39.2; P = 0.04)., Conclusions: In patients with TM, HT was a complication with a relatively low frequency, while HPT was more common. Based on the findings, HPT was more frequent in older patients receiving regular blood transfusions, thereby necessitating close monitoring of these patients.

Objective: This study aims to explore the short-term and long-term prevalence and effects of post-traumatic stress disorder (PTSD) among victims of cluster munitions., Design and Setting: A prospective 10-year longitudinal study that took place in Lebanon., Participants: Two-hundred-and-forty-four Lebanese civilian victims of submunition blasts, who were injured in 2006 and were over 18 years old, were interviewed. Included were participants who had been diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and the PTSD Checklist - Civilian Version in 2006. Interviewees were present for the 10-year follow-up., Main Outcome Measures: PTSD prevalence rates of participants in 2006 and 2016 were compared. Analysis of the demographical data pertaining to the association of long-term PTSD with other variables was performed. p Values <0.05 were considered statistically significant for all analyses (95% CI)., Results: All the 244 civilians injured by cluster munitions in 2006 responded, and were present for long-term follow-up in 2016. The prevalence of PTSD decreased significantly from 98% to 43% after 10 years (p<0.001). A lower long-term prevalence was significantly associated with male sex (p<0.001), family support (p<0.001) and religion (p<0.001). Hospitalisation (p=0.005) and severe functional impairment (p<0.001) post-trauma were significantly associated with increased prevalence of long-term PTSD. Symptoms of negative cognition and mood were more common in the long run. In addition, job instability was the most frequent socioeconomic repercussion among the participants (88%)., Conclusions: Psychological symptoms, especially PTSD, remain high in war-affected populations many years after the war; this is particularly evident for Lebanese civilians who were victimised by cluster munitions. Screening programmes and psychological interventions need to be implemented in vulnerable populations exposed to war traumas. Officials and public health advocates should consider the socioeconomic implications, and help raise awareness against the harm induced by cluster munitions and similar weaponry., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Thyroxine (T 4 ) enters the brain either directly across the blood-brain barrier (BBB) or indirectly via the choroid plexus (CP), which forms the blood-cerebrospinal fluid barrier (B-CSF-B). In this study, using isolated perfused CP of the sheep by single-circulation paired tracer and steady-state techniques, T4 transport mechanisms from blood into lateral ventricle CP has been characterized as the first step in the transfer across the B-CSF-B. After removal of sheep brain, the CPs were perfused with 125 I-T 4 and 14 C-mannitol. Unlabeled T 4 was applied during single tracer technique to assess the mode of maximum uptake ( U max ) and the net uptake ( U net ) on the blood side of the CP. On the other hand, in order to characterize T 4 protein transporters, steady-state extraction of 125 I-T 4 was measured in presence of different inhibitors such as probenecid, verapamil, BCH, or indomethacin. Increasing the concentration of unlabeled-T 4 resulted in a significant reduction in U max %, which was reflected by a complete inhibition of T 4 uptake into CP. In fact, the obtained U net % decreased as the concentration of unlabeled-T 4 increased. The addition of probenecid caused a significant inhibition of T 4 transport, in comparison to control, reflecting the presence of a carrier mediated process at the basolateral side of the CP and the involvement of multidrug resistance-associated proteins (MRPs: MRP1 and MRP4) and organic anion transporting polypeptides (Oatp1, Oatp2, and Oatp14). Moreover, verapamil, the P-glycoprotein (P-gp) substrate, resulted in ~34% decrease in the net extraction of T 4 , indicating that MDR1 contributes to T 4 entry into CSF. Finally, inhibition in the net extraction of T 4 caused by BCH or indomethacin suggests, respectively, a role for amino acid "L" system and MRP1/Oatp1 in mediating T 4 transfer. The presence of a carrier-mediated transport mechanism for cellular uptake on the basolateral membrane of the CP, mainly P-gp and Oatp2, would account for the efficient T 4 transport from blood to CSF. The current study highlights a carrier-mediated transport mechanism for T4 movement from blood to brain at the basolateral side of B-CSF-B/CP, as an alternative route to BBB.

Background: Traumatic brain injury (TBI) is a debilitating medical and emerging public health problem that is affecting people worldwide due to a multitude of factors including both domestic and war-related acts. The objective of this paper is to systematically review the status of TBI in Lebanon - a Middle Eastern country with a weak health system that was chartered by several wars and intermittent outbursts of violence - in order to identify the present gaps in knowledge, direct future research initiatives and to assist policy makers in planning progressive and rehabilitative policies., Methods: OVID/Medline, PubMed, Scopus databases and Google Scholar were lastly searched on April 15, 2016 to identify all published research studies on TBI in Lebanon. Studies published in English, Arabic or French that assessed Lebanese patients afflicted by TBI in Lebanon were warranting inclusion in this review. Case reports, reviews, biographies and abstracts were excluded. Throughout the whole review process, reviewers worked independently and in duplicate during study selection, data abstraction and methodological assessment using the Downs and Black Checklist., Results: In total, 11 studies were recognized eligible as they assessed Lebanese patients afflicted by TBI on Lebanese soils. Considerable methodological variation was found among the identified studies. All studies, except for two that evaluated domestic causes such as falls, reported TBI due to war-related injuries. Age distribution of TBI victims revealed two peaks, young adults between 18 and 40 years, and older adults aged 60 years and above, where males constituted the majority. Only three studies reported rates of mild TBI. Mortality, rehabilitation and systemic injury rates were rarely reported and so were the complications involved; infections were an exception., Conclusion: Apparently, status of TBI in Lebanon suffers from several gaps which need to be bridged through implementing more basic, epidemiological, clinical and translational research in this field in the future., Competing Interests: Authors declare no conflicts of interests.

Background: Myocardial infarction (MI) is a heart condition caused by the suspension of blood circulation in a part of the myocardium. There are different risk factors contributing to a heart attack. Some believe that endorphins and endogenous opioids play an important role in causing MIs., Objectives: This study intended to determine the relationship between opium dependency and mortality rate among patients with MI., Patients and Methods: This retrospective study investigated patients who had MI for the first time and were hospitalized in the coronary care unit (CCU) of Khatamolanbia hospital in Zahedan, Iran, from 2007 to 2010. These patients were either opium dependent or not. Four hundred patients were selected. The patients' possibilities of death and re-hospitalization after the first MI were confirmed over the phone. Data was analyzed through t-test and chi-squared test., Results: Of all the patients, 19.5% were opium-dependent. The mortality rate in the non-opium-dependent group was 5.9%, while in the dependent group this rate was 11.5% (P = 0.072). The number of re-hospitalizations due to heart problems was higher in the opium-dependent patients (P < 0.001)., Conclusions: There was no meaningful relationship between the mortality rate of patients with MI who were either opium-dependent or non-opium-dependent. The number of re-hospitalizations due to heart problems was meaningfully higher in the opium-dependent patients; hence, educating people and training them on the destructive effects of opium, specifically in patients with heart conditions is highly recommended.

Background: Cognitive disorder is a fluctuating cognitive destruction and a common problem for hospitalized patients, which leads to loss of consciousness. It is usually accompanied with increased mortality, prolonged hospital stay, and decreased rehabilitation., Objectives: The purpose of this study was to determine risk factors associated with cognitive disorder after open-heart surgery., Patients and Methods: In total, 171 patients who had undergone off-pump open-heart surgery and lacked any history of psychiatric disorders were enrolled. Samples were selected according to a purposive sampling method. The Mini-Mental State Examination questionnaire was used for these patients to assess the incidence of cognitive disorder 24 hours after the operation in ICU and to compare creatinine level, ESR, extubation time and patients' age in the two groups, one with postoperative cognitive disorder and the other without it. Independent T-test was used to compare the two groups regarding any history of diseases such as diabetes, hypertension and hyperlipidemia, Chi square test was used., Results: In total, 75% of patients had postoperative cognitive disorder. There was a significant association between the history of high blood pressure, C-reactive protein and preoperative creatinine levels in both cognitive disorder and control groups., Conclusions: Given the significant prevalence of postoperative cognitive disorder and significant associatio n between the history of high blood pressure, C-reactive protein and preoperative creatinine and cognitive disorder, detection of patient's clinical symptoms may improve diagnosis, treatment and prevention of this disorder.

We assessed lifelong environmental enrichment effects on possible age-related modifications in emotional behaviors, spatial memory acquisition, retrieval of recent and remote spatial memory, and cholinergic forebrain systems. At the age of 1 month, Long-Evans female rats were placed in standard or enriched rearing conditions and tested after 3 (young), 12 (middle-aged), or 24 (aged) months. Environmental enrichment decreased the reactivity to stressful situations regardless of age. In the water maze test, it delayed the onset of learning deficits and prevented age-dependent spatial learning and recent memory retrieval alterations. Remote memory retrieval, which was altered independently of age under standard rearing conditions, was rescued by enrichment in young and middle-aged, but unfortunately not aged rats. A protected basal forebrain cholinergic system, which could well be one out of several neuronal manifestations of lifelong environmental enrichment, might have contributed to the behavioral benefits of this enrichment.

Cln3(Δex7/8) mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3(Δex7/8) mice. Homozygous Cln3(Δex7/8) mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10-14 weeks of age. Homozygous Cln3(Δex7/8) mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12-13 week old homozygous Cln3(Δex7/8) mice, which were also seen to a lesser extent in heterozygous Cln3(Δex7/8) mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15-16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3(Δ) (ex7/8) mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3(Δ) (ex7/8) neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3(Δ) (ex7/8) mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3(Δ) (ex7/8) mice that merit further study for JNCL biomarker development.

Background: Although several strategies to predict the development of diabetes have been developed the question is whether better scores can be developed without sacrificing simplicity., Methods: Data on 3242 participants of Tehran Lipid and Glucose Study aged ≥20 years, without diabetes at the baseline that completed a ~6-year follow-up were used to develop prediction models by running a series of logistic regression model. A simple score system was then developed based on the most important variables selected with forward stepwise approach., Results: During follow-up, 231 individuals developed diabetes. The area under the receiver operating characteristic curve for the score system based on the model including systolic blood pressure (SBP), family history of diabetes, waist-to-height ratio (WHtR), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) ≥3.5 and fasting plasma glucose (FPG) levels ≥5 mmol l(-1) was 0.83 (95% CI 0.80-0.86); the model discriminated subjects with substantial risk for diabetes, appreciably better than 2-h post-challenge plasma glucose (2h-PCPG) alone (0.78; 95% CI 0.75-0.82) (P < 0.001). Scoring ≥25 yielded a positive likelihood ratio of 3.27. FPG levels even in the presence of 2h-PCPG predicted incident diabetes., Conclusion: We presented a simple model based on SBP, family history of diabetes, WHtR, TG/HDL-C and FPG; concluding that this approach is superior to relying exclusively on the 2h-PCPG for identifying individuals at high risk for developing diabetes in a Middle Eastern adult population.