First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

The nongenomic neuroprotective effects of estrogen, E2-BSA, and G1 following traumatic brain injury: PI3K/Akt and histopathological study.

OBJECTIVES: Studies suggest that both genomic and nongenomic pathways are involved in mediating the salutary effects of steroids following traumatic brain injury (TBI). This study investigated the nongenomic effects of 17ß-estradiol (E2) mediated by the PI3K/p-Akt pathway after TBI. METHODS: Ovariectomized rats were apportioned to E2, E2-BSA (E2 conjugated to bovine serum albumin), G1 [G-protein-coupled estrogen receptor agonist (GPER)] or their vehicle was injected following TBI, whereas ICI (classical estrogen receptor antagonist), G15 (GPER antagonist), ICI + G15, and their vehicles were injected before the induction of TBI and injection of drugs. Diffuse TBI was induced by the Marmarou model. Evans blue (EBC, 5 h), brain water contents (BWC), histopathological changes, and brain PI3K and p-Akt protein expressions were measured 24 h after TBI. The veterinary comma scale (VCS) was assessed before and at different times after TBI. RESULTS: The results showed a reduction in BWC and EBC and increased VCS in the E2, E2-BSA, and G1 groups. Also, E2, E2-BSA, and G1 reduced brain edema, inflammation, and apoptosis. The ICI and G15 inhibited the beneficial effects of E2, E2-BSA, and G1 on these parameters. All drugs, following TBI, prevented the reduction of brain PI3K/p-Akt expression. The individual or combined use of ICI and G15 eliminated the beneficial effects of E2, E2-BSA, and G1 on PI3K/p-Akt expressions. CONCLUSIONS: These findings indicated that PI3K/p-Akt pathway plays a critical role in mediating the salutary effects of estradiol on histopathological changes and neurological outcomes following TBI, suggesting that GPER and classic ERs are involved in regulating the expression of PI3K/p-Akt.

The effect of positive thyroglobulin antibodies on the prognosis and treatment response in patients with papillary thyroid carcinoma.

Almost 15-30% of patients with papillary thyroid carcinoma (PTC) experience some degree of recurrence after treatment. Long-term follow-up and examination after thyroidectomy are very important in dealing with this issue. Serum thyroglobulin (Tg) level and neck ultrasound are the main part of follow-up for this purpose. The presence of thyroglobulin antibodies (TgAbs) leads to unreliable thyroglobulin (Tg) levels. The present study aims to evaluate the relationship between the simultaneous measurement of Tg and TgAb with long-term survival and response to treatment in these patients. This study was conducted by surveying available data from the medical records of 204 out of 600 patients over a 20-year period. In this research, 104 patients with positive TgAb were considered as the case group, and 100 patients with negative TgAb were selected as the control group. The relationship of TgAb titer was investigated with the staging, response to treatment (including the surgery number, number of radiotherapies, and dose of radioactive iodine), and recurrence in these patients. Also, the trend of TgAb changes was examined in the presence of high or low thyroglobulin levels during the follow-up period. Patients with high TgAb levels had more lymph node involvement, higher cumulative dose, a higher number of times received iodine, more surgical number, higher recurrence rate, and less excellent response (ER) to treatment during follow-ups. This effect of TgAb worsened in the presence of high Tg titer and remained up to 36 months. Overall, the baseline level of TgAb and its changes can be a suitable factor for predicting subsequent response to treatment and recurrence in patients with PTC. Accordingly, in cases with high TgAb and Tg levels, close follow-up should be considered up to Tg and TgAb normalization.

Fragmented QRS, a strong predictor of mortality and major arrhythmic events in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study. Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0. Results: Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p < 0.0001). Conclusion: Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM.

Protamine as a barrier against the angiogenic effect of insulin: a possible role of apelin.

Insulin is proved to have angiogenic ability thereby may worsen the diabetic retinopathy (DR) progression. Insulin also triggers the expression of endogenous angiogenic peptide, apelin. Since protamine was introduced as an inhibitor of the apelin receptor, we hypothesized that use of protaminated insulin instead of non-protaminated insulin can decrease the negative role of insulin in progression of DR. Firstly, the incidence of DR was compared among three diabetic patient groups: an oral medication, non-protaminated insulin, and protaminated insulin (PIns). Proliferation and migration rate of HUVECs was measured after insulin, apelin, and protamine exposure. In clinical study, the chance of developing DR was 8.5 and 4.1 times higher in insulin group and PIns groups compared with oral group respectively. Insulin group had a chance of 9.5-folds of non-proliferative DR compared to oral group. However, the difference of non-proliferative DR between PIns and oral group wasn't significant. In-vitro tests showed that concomitant use of insulin and apelin increases viability and migratory potential of HUVECs. However, protamine could reverse this effect. Protamine present in some insulins might show a promising protective role against diabetic retinopathy. Thus, protaminated insulins may be preferable in the treatment of diabetes.

Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway.

BACKGROUND: Studies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway. MATERIAL AND METHODS: Marmarou method was utilized to induce diffuse TBI in ovariectomized rats. P4 (1.7 mg/kg) or the vehicle (oil) was administered 30 min after TBI induction. Moreover, RU486 (PR antagonist) and its vehicle (DMSO) were injected before TBI induction and P4 injection. Brain Evans blue content, brain water content (WC), various oxidative stress parameters, IL-1ß levels, tumor necrosis factor-α (TNF-α), histopathological alterations, and also phosphorylated Akt (p-Akt) and PI3K expressions in the brain were assessed 24 h after TBI. The veterinary comma scale (VCS) was measured before and after TBI at different times. RESULTS: The findings revealed that P4 caused an increase in VCS and a decrease in brain WC, oxidative stress, TNF-α and IL-1ß levels. RU486 inhibited the beneficial effects of P4 on these indices. Moreover, RU486 prevented the reduction of brain edema, inflammation, and apoptosis caused by P4. Moreover, P4 following TBI increased the expression of PI3K/p-Akt protein in the brain. RU486 eliminated the effects of P4 on PI3K/p-Akt expression. CONCLUSION: According to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro-inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p-Akt expression and nongenomic function of P4.

Carvacrol decreases blood-brain barrier permeability post-diffuse traumatic brain injury in rats.

Previously, we showed that Satureja Khuzestanica Jamzad essential oil (SKEO) and its major component, carvacrol (CAR), 5-isopropyl-2-methylphenol, has anti-inflammatory, anti-apoptotic, and anti-edematous properties after experimental traumatic brain injury (TBI) in rats. CAR, predominantly found in Lamiaceae family (Satureja and Oregano), is lipophilic, allowing diffusion across the blood-brain barrier (BBB). These experiments test the hypothesis that acute treatment with CAR after TBI can attenuate oxidative stress and BBB permeability associated with CAR's anti-edematous traits. Rats were divided into six groups and injured using Marmarou weight drop: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg) and CAR200-naive treated rats. Intraperitoneal injection of vehicle or CAR was administered thirty minutes after TBI induction. 24 h post-injury, brain edema, BBB permeability, BBB-related protein levels, and oxidative capacity were measured. Data showed CAR 200 mg/kg treatment decreased brain edema and prevented BBB permeability. CAR200 decreased malondialdehyde (MDA) and reactive oxygen species (ROS) and increased superoxide dismutase (SOD) and total antioxidative capacity (T-AOC), indicating the mechanism of BBB protection is, in part, through antioxidant activity. Also, CAR 200 mg/kg treatment suppressed matrix metalloproteinase-9 (MMP-9) expression and increased ZO-1, occludin, and claudin-5 levels. These data indicate that CAR can promote antioxidant activity and decrease post-injury BBB permeability, further supporting CAR as a potential early therapeutic intervention that is inexpensive and more readily available worldwide. However, more experiments are required to determine CAR's long-term impact on TBI pathophysiology.

Organochlorine pesticides and epigenetic alterations in thyroid tumors.

Purpose: Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients. Methods: OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis. Results: Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P<0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P<0.001) and H4K16 (OR=6.03, P<0.001) acetylation. Conclusion: The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.

Organochlorine pesticides induce thyroid tumors through oxidative stress; an in vivo and in silico study.

Thyroid disease is one of the most common endocrine problems around the world. Among the numerous factors, exposure to environmental elements such as pesticides is associated with an increase in the incidence of thyroid disorders. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) in induction of oxidative stress (OS) and development of thyroid tumors. This case-control study was conducted on 61 patients with papillary thyroid carcinoma (PTC), 70 patients with benign thyroid nodules (BTN), and 73 healthy individuals as control. Seven derived OCPs residues measured by gas chromatography (GC), and enzyme activities of acetylcholinesterase (AChE), superoxide dismutase3 (SOD3), catalase (CAT), glutathione peroxidase3 (GPx3) and paraoxonase1 (PON1) and also, non-enzymatic antioxidant including; malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), and nitric oxide (NO) biomarkers in all participants were investigated. Furthermore, all of the above enzymes were docked against measured OCPs. The results revealed that ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4-DDT, and 4,4-DDT levels along with MDA, NO, and PC levels were elevated, while AChE, SOD3, GPx3, CAT, and PON1 activities and TAC levels were decreased in the PTC and BTN groups compared with the control group. Therefore, OCPs might play a role in the development of thyroid tumors through several mechanisms including generation of OS. Importantly, in silico analysis confirmed the in vivo findings.

Factors associated with treatment adherence to treatment among in patients with type 2 diabetes in Iran: A cross-sectional study.

Introduction: Diabetes is a chronic metabolic disorder that affects millions of people worldwide. Adherence to treatment is a key determinant to proper management. This study aimed to assess the factors associated treatment adherence in patients with type 2 diabetes. Materials and methods: We conducted this cross-sectional study on 704 patients with type 2 diabetes referred to three diabetes clinics in Kerman, Iran. We used treatment adherence questionnaire and functional communicative critical health literacy (FCCHL) to collect data and descriptive statistics, as well as Pearson correlation coefficient and multivariate regression analysis to analyze data. Significance level was <0.05. Results: The study results showed that health literacy, HbA1c, and income were main predictors of diabetes treatment adherence. The patients' adherence increased as their health literacy increased. The patients' HbA1c decreases as their adherence increased. We found a 2.54-point increase in the treatment adherence score for those with sufficient income and a 0.76-point increase in the treatment adherence score for those with relatively sufficient income compared with those with insufficient income. Conclusion: We found several factors affecting diabetes treatment adherence. Planning theory-based interventions can be helpful to improve the determinants.

Determinants of Poor Treatment Adherence among Patients with Type 2 Diabetes and Limited Health Literacy: A Scoping Review.

Prevention of complications and successful control of diabetes require preventive and therapeutic measures. Patients' nonadherence to medication and diet regimens and healthcare protocols is associated with significant therapeutic and economic consequences. The present scoping review aims to identify determinants of poor treatment adherence among patients with type 2 diabetes and limited health literacy in 2021. This scoping review was conducted in five stages: designing a research question, searching and extracting related studies, selecting related studies, tabulating information, and reporting results. Data were collected from six foreign electronic databases (Embase, Science Direct, PubMed, Google Scholar, Scopus, and Web of Science) and four Iranian electronic databases (MagIran, SID, IranDoc, and IranMedex) using keywords "Type 2 diabetes", "barriers", "treatment", "medication", "adherence", "non-adherence", "limited adherence", and "limited health literacy" from January 2010 to November 2021. From an initial 146 articles, 18 articles were eligible for review. Eighteen studies involving 3925 patients with T2DM from eight countries were included. The prevalence of nonadherence ranged from 42% to 74.3%. Barriers to treatment adherence, which were common among the articles, included economic problems, poor communication with healthcare team, lack of family support, lack of knowledge, misconceptions, and limited health literacy. The results of the present study provided modifiable and nonmodifiable factors affecting treatment adherence among patients with type 2 diabetes. Modifiable factors are essential by performing appropriate interventions with the target group and health professionals.

Thyroid Cancer-Specific Health-Related Quality of Life Questionnaire: Psychometric Properties of the Persian Version.

Background: Adverse effects related to treatment negatively affect the quality of life of patients with thyroid cancer. The current study aimed to evaluate the psychometric properties of the Persian version of the thyroid-cancer-specific health-related quality of life (TC-specific HRQoL) questionnaire among patients with thyroid cancer in Kerman province, Iran. Methods: This research was a cross-sectional study conducted on 240 patients with thyroid cancer in Kerman province from 2000 to 2015. The patients were selected through the census method and were asked to complete the thyroid-cancer-specific quality of life questionnaire. Data were analyzed by SPSS version 19.0 and LISREL version 8.80. The reliability of the Persian version was determined by Cronbach's α coefficient and the intraclass correlation coefficient (ICC). Exploratory and confirmatory factor analysis (CFA) was also conducted. Results: The Cronbach's α and ICCs were determined as 0.92 and 0.88, respectively. Five factors were extracted in the exploratory factor analysis with a total of 55.76% explained variance. Acceptable goodness of fit indices were found in CFA. Conclusions: The Persian version of the TC-specific HRQoL has sufficient psychometric properties and can be used to assess HRQoL among patients with thyroid cancer.

Substitution of calorie restriction for protective effects of estrogen on cardiometabolic risk factors and oxidative stress in obese postmenopausal rat model.

Estrogen has an anti-obesity effect and plays an important role in improving cardiometabolic disorders. Weight loss and reduction in calorie intake impede the development of obesity-related cardiometabolic risk factors. Therefore, we investigated the substitution of calorie restriction for effects of estrogen on cardiometabolic risk factors and oxidative stress in obese postmenopausal rat model. In this study, adult female Wistar rats were allocated into Sham and ovariectomized (OVX) groups and were given standard diet (SD) or 60% high-fat diet (HFD) or 30% calorie restriction (CR) for 16 weeks, following this, animals received E2 (17-ß estradiol; 1 mg/kg; i.p.) every four days for 4 weeks. Results showed that HFD elevated the body weight, BMI, food intake, and blood glucose (BG) level in both sham and OVX groups. In addition, HFD had negative effects on lipid profile and oxidative stress in these groups. Whereas CR decreased these indices in both Sham and OVX groups fed an HFD, it could not diminish the BG level in the OVX-HFD group. E2 treatment in OVX animals with or without CR reduced body weight, BMI, food intake, and BG level, and also had positive effects on lipid profile alterations and oxidative stress reduction. In comparison, no significant differences were observed regarding the effects of E2 with CR between two groups for body weight, lipid profile, BG, and oxidative stress in the OVX-HFD rats. Overall, CR prevents and ameliorates cardiometabolic risk factors induced by obesity in postmenopausal conditions and is also a good candidate for E2 substitution.

Factors affecting nonadherence to treatment among type 2 diabetic patients with limited health literacy: Perspectives of patients, their families, and healthcare providers.

BACKGROUND: Treatment adherence is one of the behaviors associated with type 2 diabetes that predicts whether it will be successfully treated or develop complications and become uncontrolled. This study aimed to determine factors affecting nonadherence to treatment among diabetic patients with limited health literacy from the perspectives of patients, their families, and healthcare providers. MATERIALS AND METHODS: This qualitative study with a content analysis approach was conducted on 84 eligible type 2 diabetes patients with limited health literacy and poor adherence to treatment, as well as their families and healthcare providers using a purposive sampling method, in Kerman city in 2021. Interviews were conducted using a semistructured interview guide with a broad, open-ended question to provide a general history of the disease separately. The interviewer asked participants to identify the perceived barriers to treatment nonadherence. Each interview lasted 45-60 min. MAXQDA version 20 and inductive content analysis were used to code and analyze extracted data. RESULTS: Four major themes emerged from the patients' perspectives as "financial problems," "individual factors," "problems related to medication availability," and "healthcare providers' poor practices." Two major themes were classified from the perspective of patients' families as "financial problems" and "Individual factors," and four major themes were identified from the viewpoint of healthcare providers including "financial problems," "individual factors," "scarcity and medication availability," and "poor practice of the healthcare provider." These mentioned barriers were confirmed regarding treatment nonadherence among study participants. CONCLUSION: Study findings revealed different factors of treatment nonadherence among diabetic patients with limited health literacy. Therefore, these factors should be considered in tailoring promotive educational and supportive interventions. Considering the importance of adherence to treatment patients, planning empowerment family-based interventions focusing on health literacy improvement seems necessary.

External Validation of Finnish Diabetes Risk Score and Australian Diabetes Risk Assessment Tool Prediction Models to Identify People with Undiagnosed Type 2 Diabetes: A Cross-sectional Study in Iran.

Background: Noninvasive risk prediction models have been widely used in various settings to identify individuals with undiagnosed diabetes. Objectives: We aimed to evaluate the discrimination, calibration, and clinical usefulness of the Finnish Diabetes Risk Score (FINDRISC) and Australian Diabetes Risk Assessment (AUSDRISK) to screen undiagnosed diabetes in Kerman, Iran. Methods: We analyzed data from 2014 to 2018 in the second round of the Kerman Coronary Artery Disease Risk Factors Study (KERCADRS), Iran. Participants aged 35 - 65 with no history of confirmed diabetes were eligible. The area under the receiver operating characteristic curve (AUROC) and decision curve analysis were applied to evaluate the discrimination power and clinical usefulness of the models, respectively. The calibration was assessed by the Hosmer-Lemeshow test and the calibration plots. Results: Out of 3262 participants, 145 (4.44%) had undiagnosed diabetes. The estimated AUROCs were 0.67 and 0.62 for the AUSDRISK and FINDRISC models, respectively (P < 0.001). The chi-square test results for FINDRISC and AUSDRISC were 7.90 and 16.47 for the original model and 3.69 and 14.61 for the recalibrated model, respectively. Based on the decision curves, useful threshold ranges for the original models of FINDRIS and AUSDRISK were 4% to 10% and 3% to 13%, respectively. Useful thresholds for the recalibrated models of FINDRISC and AUSDRISK were 4% to 8% and 4% to 9%, respectively. Conclusions: The original AUSDRISK model performs better than FINDRISC in identifying patients with undiagnosed diabetes and could be used as a simple and noninvasive tool where access to laboratory facilities is costly or limited.

Asymptomatic COVID-19 as a Risk Factor of Diabetic Ketoacidosis and Mucormycosis: A Case Report and Review of the Literature.

Mucormycosis is a lethal and life-threatening fungal infection. Several cases describing the association of COVID-19 and mucormycosis have been reported. In this article, we report a 58-year-old female with a history of diabetes mellitus type 2 who presented by diabetic ketoacidosis, rhino-orbital mucormycosis, and COVID-19. The patient was treated with liposomal amphotericin B and debridement of necrotic tissue of the rhino-orbital area and paranasal sinuses. Unfortunately, she passed away a few days after orbital surgery. We also conducted a review of the literature and reported 3 other similar cases that suffered from mucormycosis in association with COVID-19 and diabetic ketoacidosis and discussed the importance of this association.

Prevalence and Incidence Rate of Diabetes, Pre-diabetes, Uncontrolled Diabetes, and Their Predictors in the Adult Population in Southeastern Iran: Findings From KERCADR Study.

Background: Diabetes mellitus is among the most serious health challenges worldwide. We assessed the prevalence of pre-diabetes (pre-DM) and diabetes (DM), the effectiveness of diabetes management, the 5-year incidence rate, and associated variables in the adult population in southeastern Iran. Methods: In a random cluster household survey (2014-2018), 9,959 adult individuals aged 15-80 years were assessed for coronary artery disease risk factors, including diabetes mellitus in Kerman (KERCADRS, phase 2). Among these people, 2,820 persons had also participated in phase 1 of the study 5 years earlier (2009-2011). Univariable and multivariable survey logistic regression models were used to identify the potential predictors of diabetes and pre-diabetes. Results: The prevalence of pre-DM was 12% (males 13.2% vs. females 11.1%), steadily increasing from 7.1% in the 15-24 years group to 18.4% in the 55-64 years group. The prevalence of DM was 10.2% (male and female, 7.9 and 10.8%, respectively), of which 1.9% were undiagnosed. DM was diagnosed in 10.6% of educated and 15.1% of illiterate people. The prevalence of diagnosed DM was lower in smokers (5.2 vs. 8.7%) and dependent opium users (5.4 vs. 8.8%). The prevalence of uncontrolled DM (HbA1c > 7%) was 48.8%, increasing with age. The frequency of uncontrolled DM among people without and with treatment was 32 and 55.9%, respectively. Illiterate people had worse uncontrolled DM (55.6 vs. 39.6%). The 5-year incidence rate (persons/100 person-years) was 1.5 for pre-DM and 1.2 for DM, respectively. The lowest and the highest incidence rate of DM belonged to the 15-34 years old group (0.5) and dependent opium users (2.4). The incidence rate was found to have a direct relationship with BMI and a reverse relationship with physical activity. Conclusion: Pre-DM and DM affected 22.2% of the population. One-third of patients with diabetes had undiagnosed DM, and in 55.9% of people with diagnosed DM, treatment had been ineffective. Appropriate health interventions are needed to reduce the prevalence and health consequences of diabetes in the region.

Henoch-Schönlein Purpura (IgA Vasculitis) in Association with Thyrotoxicosis.

Graves' disease is the most common cause of hyperthyroidism, which is characterized by thyroid antibodies and the following clinical manifestations: goiter, ophthalmopathy, and pretibial myxedema. On the other hand, Henoch-Schönlein purpura is an IgA-mediated small-vessel vasculitis. Review of the literature showed a relationship between propylthiouracil overdose and the following Henoch-Schönlein purpura (IgA vasculitis) as a side effect. The patient was a 31-year-old woman with a chief complaint of tremor and significant weight loss who contracted pruritic palpable purpura during her disease course. Then, she underwent the treatment of hyperthyroidism by methimazole which intensified her cutaneous lesions. The diagnosis of Henoch-Schönlein purpura (IgA vasculitis) was confirmed after skin biopsy. Finally, she was treated with colchicine, prednisolone, and radioiodine ablation, which caused her lesions to disappear. The temporal priority of pruritic palpable skin lesions to hyperthyroidism treatment with methimazole suggested that Henoch-Schönlein purpura (IgA vasculitis) was related to hyperthyroidism and was intensified by antithyroid agents in this patient.

Distribution of Myeloid and Plasmacytoid Dendritic Cell Subpopulations in Peripheral Blood of Hyperprolactinemic Women.

Dendritic cells (DCs) play key roles in regulating the immune response using the specialized function of processing and presenting antigens. Prolactin (PRL), a hormone produced by the pituitary gland, participates in DC maturation and function. The present study was aimed to determine the frequencies of peripheral blood DC subpopulations of myeloid DC (MDC) and plasmacytoid DC (PDC) in hyperprolactinemic (HPRL) women compared to normal healthy volunteers. This study was conducted on 70 women, including 35 HPRL patients and 35 matched healthy controls, whose PRL serum levels were in the normal range (lower than 25 ng/mL). Serum thyroid-stimulating hormone (TSH) levels were measured in both groups as an indicator of normal thyroid function. The electrochemiluminescence immunoassay method was applied to measure the serum levels of TSH and PRL. The frequencies of MDC and PDC in the peripheral blood samples of both groups were determined by flow cytometry. The mean serum PRL levels in the HPRL patients and healthy individuals were 46.41±21.96 and 13.75±11.19, respectively (p<0.0001); however TSH levels in both groups were similar and within the normal range (0.4-4.5 mIU/mL) (p=0.2). The frequencies of both MDC and PDC subpopulations in the peripheral blood of HPRL patients were significantly lower than they were in the healthy controls. However, the ratio of MDCs/PDCs in HPRL patients was not significantly different between the two groups (p=0.8). Our study revealed that an increased level of serum PRL may lead to a reduction in the number of MDC and PDC subpopulations. These results could help clarify the complex relationship between the immune system and the neuroendocrine axis and may be of potential use in understanding the pathogenesis of endocrine and immune disorders.

The effect of IFN-ß 1a on expression of MDA5 and RIG-1 in multiple sclerosis patients.

The aims of this study were to compare mRNA levels of melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) in multiple sclerosis (MS) patients in comparison to the healthy controls as well as investigating the effects of IFN-ß 1a on the expression of these molecules. In this study, mRNA levels of MDA5 and RIG-1 in peripheral leukocytes of 30 new cases of MS patients and 35 healthy controls were evaluated using the real-time-PCR method. mRNA levels of MDA5 and RIG-1 were determined in the MS patients 6 months after treatment with standard doses of IFN-ß 1a. mRNA levels of MDA5 and RIG-1 were significantly decreased in the MS patients in comparison to the healthy controls. The analysis also revealed that IFN-ß 1a therapy leads to the upregulation of RIG-1, but not MDA5, in the total MS patients and the female group. MS patients suffer from insufficient expression of MDA5 and RIG-1, and IFN-ß 1a therapy results in the upregulation of RIG-1 in the patients, especially in the female patients. Thus, it seems that IFN-ß 1a not only decreased pathogenic inflammatory responses but also modulated the expression of RIG-1 to protect the patients from infectious diseases and upregulation of IFN-I in a positive feedback.