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 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.

Downregulation of IL-22 can be considered as a risk factor for onset of type 2 diabetes.

There is some controversy as for the roles played by tumor growth factor-ß (TGF-ß), interleukin-1ß (IL-1ß), and IL-22 in the onset process of type 2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF-ß, IL-1ß, and IL-22 in the new cases and long period T2D patients as well as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D patients who have suffered from the disease more than 2 years (group 2), and 104 healthy controls have been selected from 6240 (3619 females) patients who were under study population from Kerman Coronary Artery Disease Risk Factor Study. Serum levels of TGF-ß, IL-1ß, and IL-22 have been evaluated using commercial kits. Serum levels of TGF-ß and IL-1ß significantly increased, while IL-22 decreased in 2 groups in comparison to healthy controls. Serum levels of IL-22, but not TGF-ß and IL-1ß, were significantly decreased in group 1 in comparison to healthy controls. There were no significant differences between groups 1 and 2 as for the cytokine levels. Serum levels of IL-22 increased in the females in group 2 when compared to females in group 1. It appears that TGF-ß and IL-1ß participate in the induction of inflammation after establishment of T2D, while decrease in IL-22 may be considered as a key factor for onset of the disease. Gender can also be considered as the main risk factor for variation in cytokine levels.

ENHANCED BETA-CATENIN EXPRESSION IS ASSOCIATED WITH RECURRENCE OF PAPILLARY THYROID CARCINOMA.

OBJECTIVE: A direct role of ß-catenin 1 (ß-cat) in the proliferation of human thyroid tumor cells has been identified. This study aimed to determine if there is an association between ß-cat gene expression and the staging, recurrence, metastasis, and disease-free survival of papillary thyroid cancer. METHODS: A retrospective cohort study was conducted using data from available information in the medical records and paraffin blocks of 81 of 400 patients referred to the endocrine clinic over a 10-year period. Real-time polymerase chain reaction was used to evaluate ß-cat gene expression. Disease-free survival was assessed using the Kaplan-Meier method. RESULTS: The 10-year survival rate in these patients was 98.25%, and disease-free survival was 48.1%. Cumulative dose of radioactive iodine that patients received was significantly and positively correlated with ß-cat gene expression ( r = -0.2; P = .03). Also, in patients with recurrence, ß-cat gene expression was higher and statistically significant (5-fold increase; P = .002). Patients in more advanced stage and those with recurrence/distant metastasis had higher ß-cat gene expression. We found that the patients had a better survival (lower recurrence) if they had a lower ß-cat gene expression (SD, 0.142 to 0.052) (Mantel-Cox test, P = .002). CONCLUSION: We conclude that ß-cat gene expression is positively correlated with recurrence, distant metastasis, and tumor-node-metastasis stage. ABBREVIATIONS: ß-cat = ß-catenin 1; CI = confidence interval; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic.

Interferon-ß 1a Modulates Expression of RAGE but Not S100A12 and Nuclear Factor-κB in Multiple Sclerosis Patients.

OBJECTIVES: Interferon-ß 1a (IFN-ß 1a) is a common strategy therapy for multiple sclerosis (MS) with unknown mechanisms. S100A12 (S100 calcium-binding protein A12) is a damage-associated molecular pattern molecule which binds to its receptor, RAGE (receptor for advanced glycation end products), and activates nuclear factor-κB (NF-κB). NF-κB is transcribed from proinflammatory molecules, which may participate in the pathogenesis of MS. Therefore, the aims of this study were to compare mRNA levels of S100A12, RAGE, and NF-κB in newly diagnosed MS patients with healthy controls and determine whether IFN-ß 1a therapy affects the expression of the molecules. METHODS: S100A12, RAGE, and NF-κB mRNA levels in 30 new cases of untreated MS patients and 35 healthy controls were evaluated using the real-time PCR technique. The mRNA levels were also evaluated in the MS patients after 6 months of IFN-ß 1a therapy. RESULTS: S100A12, RAGE, and NF-κB mRNA levels were significantly decreased in the new cases of untreated MS patients in comparison to healthy controls. IFN-ß 1a therapy results in upregulation of RAGE in MS patients, but not S100A12 and NF-κB. CONCLUSIONS: It appears that S100A12 participates in the pathogenesis of MS, and it seems that IFN-ß 1a modulates immune responses in an S100A12-independent manner. Based on the reported anti-inflammatory effects of RAGE, it seems that RAGE may be considered as a mechanism by IFN-ß 1a to modulate immune responses. NF-κB is produced permanently in the human cells and is inactive in the cytoplasm; therefore, the effects of IFN-ß 1a may be related to its functions rather than expressions.

HYPERTHYROIDISM AND HYPERPROLACTINEMIA: IS THERE ANY ASSOCIATION?

OBJECTIVE: To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism. METHODS: Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age. RESULTS: The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001). CONCLUSION: The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism. ABBREVIATIONS: PRL = prolactin T4 = thyroxine TRH = thyrotropin-releasing hormone TSH = thyroid-stimulating hormone.

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 association between heavy metal exposure and obesity: A systematic review and meta-analysis.

Background: Obesity and metabolic syndrome are global health concerns associated with development of different types of diseases and serious health threats in the long term. Their metabolic imbalance can be attributable to inherited and environmental factors. As a considerable environmental agent, heavy metals exposure can predispose individuals to diseases like obesity. This systematic review and meta-analysis aimed to evaluate the association between heavy metals exposure and the risk of obesity. Methods: PubMed/MEDLINE, EMBASE and Web of Science were systematically searched until December 17, 2022. Only observational studies that evaluated heavy metals exposure and obesity were included. Studies were excluded if they assessed maternal or prenatal exposure, the mixture of heavy metals and other chemicals, reported the association with overweight or other diseases, and undesirable study designs. The Joanna Briggs Institute checklist was used for quality assessment. The pooled adjusted odds ratio (aOR) and the pooled standardized mean difference (SMD) with their 95% confidence intervals (CIs) were calculated, respectively. The publication bias was evaluated using Egger's and Begg's tests. Results: Twenty studies (n = 127755), four case-control and sixteen analytical cross-sectional studies, were included. Lead exposure was significantly associated with a lower risk of obesity (aOR: 0.705, 95% CI: 0.498-0.997), while mercury (aOR: 1.458, 95% CI: 1.048-2.031) and barium (aOR: 1.439, 95% CI: 1.142-1.813) exposure increased the risk of obesity. No significant publication bias was found and the studies had a low risk of bias. Conclusion: Overall, lead exposure reduced obesity risk, while mercury and barium exposure raised it. Further large-scale observational studies are recommended to determine the roles of heavy metals in obesity.Study registration ID: CRD42023394865. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-023-01307-0.

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.

Evaluation of effect of acarbose consumption on weight losing in non-diabetic overweight or obese patients in Kerman.

BACKGROUND: High prevalence of obesity and the importance of this issue as a risk factor for chronic diseases such as severe cardiovascular diseases, diabetes, and cancer necessitate the need for treatment. The aim of this study was the evaluation of acarbose effect on the weight loss in non diabetic overweight or obese patients in Kerman. MATERIALS AND METHODS: A double blind randomized controlled clinical trial was performed on 66 patients with the body mass index (BMI) between 25 and 35 kg/m(2). Patients were divided in treatment and control groups using the randomization. The treatment group took 100 mg acarbose 3 times a day for 20 weeks in combination with the low calorie diet and exercise. Control group was given placebo, low calorie diet, and exercise. BMI was measured after 20 weeks. The analyses were carried out using t-test and repeated measured ANOVA. RESULTS: Patients in acarbose and placebo group had a non significant difference in BMI at baseline. Reducing in weight was considered in every month in both groups, but this reduction was higher in the treatment group. At the 5(th) month, the difference of BMI in the treatment group was significantly lower than the placebo group (2.31 ± 0.6 vs. 0.76 ± 0.6 kg/m(2), P < 0.001). CONCLUSION: Acarbose, especially in combination with the low calorie diet and exercise, seems to lose weight effectively in obese and overweight patients in communities that have a high carbohydrate intake (like Persian diet).

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.

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.

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.

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.

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.

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.

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.

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.