Barriers Toward the National Program for Prevention and Control of Diabetes in Iran: A Qualitative Exploration.

BACKGROUND: Despite the achievements of the national program for the prevention and control of diabetes (NPPCD) over the past two decades, the available evidence indicates a high prevalence of this disease in Iran. This qualitative study aims to investigate barriers to the NPPCD by pursuing the perspectives of relevant policy-makers, planners, and healthcare workers. METHODS: A grounded theory approach was used to analyze participants' perceptions and experiences. Semi-structured interviews (n=23) and eight focus groups (n=109) were conducted with relevant policy-makers, planners, and healthcare workers in charge of Iran's national diabetes management program. Of the 132 participants, ages ranged from 25 to 56 years, and 53% were female. Constant comparative analysis of the data was conducted manually, and open, axial, and selective coding was applied to the data. RESULTS: Two main themes emerged from data analysis: implementation barriers and inefficient policy-making/ planning. Insufficient financial resources, staff shortage and insufficient motivation, inadequate knowledge of some healthcare workers, and defects in the referral system were recognized as the NPPCD implementation barriers. Inappropriate program prioritizing, the lack of or poor intersectoral collaboration, and the lack of an effective evaluation system were the inefficient policy-making/planning problems. CONCLUSION: Current results highlighted that inefficient policy-making and planning have led to several implementation problems. Moreover, the key strategies to promote this program are prioritizing the NPPCD, practical intersectoral collaboration, and utilizing a more efficient evaluation system to assess the program and staff performance.

Association between serum Vitamin D levels and prognostic factors in nonmetastatic breast cancer patients.

Background: Breast cancer is among the most common malignancies in women around the world. There is evidence of high prevalence of serum/blood Vitamin D deficiency in Iranian women. Considering the multitude of factors that may be involved in the prognosis and lifespan of breast cancer patients, this study investigated the level of Vitamin D in Iranian patients with nonmetastatic breast cancer. Materials and Methods: This cross-sectional study was carried out on 214 women diagnosed with breast cancer, who were referred to the radio-oncology department. Serum Vitamin D level of the patients was measured. Prognostic factors were determined based on demographic and pathological characteristics. The results were analyzed using descriptive statistics tests, Chi-square, one-way analysis of variance, Kaplan-Meier, and Cox regression model in SPSS v22. For all cases, the significance level was considered to be P < 0.05. Results: The total mean of 25-hydroxyvitamin D serum level was 25.15 ± 17.68 ng/ml. There was no significant relationship between levels of Vitamin D with disease stage, tumor size, tumor grade, estrogen receptor, progesterone receptor, and Human epidermal growth factor receptor 2 (P > 0.05). The mean survival time was 5 years and 45 days. Conclusion: No relationship was found between serum Vitamin D levels and the factors affecting the prognosis of nonmetastatic breast cancer. The Cox analysis showed that the survival time was not influenced by Vitamin D as a prognosis factor.

Association of Dietary Diabetes Risk Reduction Score With Risk of Cardiovascular Diseases in the Iranian Population: Tehran Lipid and Glucose Study.

BACKGROUND: There are no data available regarding the association of dietary diabetes risk reduction score (DDRRS) and risk of cardiovascular disease (CVD) worldwide. We aimed to investigate the association of the DDRRS with the risk of CVD outcomes in a prospective population-based study. METHOD: Individuals without CVD (n=2,195) were recruited from participants of the Tehran Lipid and Glucose Study (2006-2008) and followed for a mean of 6.7 years. The DDRRS was determined on the basis of eight components using a validated 168-item food frequency questionnaire. Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate the hazard ratios and 95% confidence interval (CI) of CVD across quartiles of DDRRS. RESULTS: The mean ± standard deviation age of participants (44.8% male) was 38.8±13.0 years at baseline. Median DDRRS for all patients was 23 (intequartile range 20-26). During follow-up, 77 (3.5%) new cases of CVD were identified. After adjustment for confounding variables, including age, sex, body mass index, physical activity, smoking, energy intake, diabetes, and hypertension, no association was found between DDRRS and risk of CVD (odds ratio, 0.70; 95% CI, 0.36-1.37 [p-value for trend=0.351]). CONCLUSIONS: The findings of this study showed that higher DDRRS is not associated with risk of CVD events.

RdRp inhibitors and COVID-19: Is molnupiravir a good option?

Rapid changes in the viral genome allow viruses to evade threats posed by the host immune response or antiviral drugs, and can lead to viral persistence in the host cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme in RNA viruses, which is involved in RNA synthesis through the formation of phosphodiester bonds. Therefore, in RNA viral infections such as SARS-CoV-2, RdRp could be a crucial therapeutic target. The present review discusses the promising application of RdRp inhibitors, previously approved or currently being tested in human clinical trials, in the treatment of RNA virus infections. Nucleoside inhibitors (NIs) bind to the active site of RdRp, while nonnucleoside inhibitors (NNIs) bind to allosteric sites. Given the absence of highly effective drugs for the treatment of COVID-19, the discovery of an efficient treatment for this pandemic is an urgent concern for researchers around the world. We review the evidence for molnupiravir (MK-4482, EIDD-2801), an antiviral drug originally designed for Alphavirus infections, as a potential preventive and therapeutic agent for the management of COVID-19. At the beginning of this pandemic, molnupiravir was in preclinical development for seasonal influenza. When COVID-19 spread dramatically, the timeline for development was accelerated to focus on the treatment of this pandemic. Real time consultation with regulators took place to expedite this program. We summarize the therapeutic potential of RdRp inhibitors, and highlight molnupiravir as a new small molecule drug for COVID-19 treatment.

Dietary acid load and risk of cardiovascular disease: a prospective population-based study.

BACKGROUND AND AIM: Considering the inconsistencies in the cardiovascular effects of dietary acid load and the impact of dietary acidity on the acid-base homeostasis within the body, we aimed to assess the association of dietary acid load and the risk of cardiovascular disease (CVD) in a prospective community-based study. MATERIALS AND METHODS: Participants (n = 2369) free of CVD at baseline (2006-2008) were included from the Tehran Lipid and Glucose Study (TLGS) and followed up for a mean of 6.7 ± 1.4 years. Dietary intakes of the participants were assessed using a semi-quantitative food frequency questionnaire (FFQ). The dietary acid load was evaluated by Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) scores. Both scores have used the macronutrient and micronutrient data of the Food Frequency Questionnaires. Multivariate Cox proportional hazard regression models were used to estimate the 6-years incident risk of CVDs across tertiles of PRAL and NEAP scores. RESULTS: Mean age and body mass index of participants were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m2 at baseline. Within 6.7 ± 1.4 years of follow-up, 79 cases of cardiovascular events were reported. NEAP was significantly associated with the incidence of CVDs (HRs = 0.50, CI 0.32-0.96; P for trend = 0.032); however, after adjusting for potential confounders, no significant associations were observed between PRAL and NEAP scores and the risk of CVDs. CONCLUSIONS: This study failed to obtain independent associations between dietary acid load and the incidence of CVDs among an Asian population.

Angiogenesis-related non-coding RNAs and gastrointestinal cancer.

Gastrointestinal (GI) cancers are among the main reasons for cancer death globally. The deadliest types of GI cancer include colon, stomach, and liver cancers. Multiple lines of evidence have shown that angiogenesis has a key role in the growth and metastasis of all GI tumors. Abnormal angiogenesis also has a critical role in many non-malignant diseases. Therefore, angiogenesis is considered to be an important target for improved cancer treatment. Despite much research, the mechanisms governing angiogenesis are not completely understood. Recently, it has been shown that angiogenesis-related non-coding RNAs (ncRNAs) could affect the development of angiogenesis in cancer cells and tumors. The broad family of ncRNAs, which include long non-coding RNAs, microRNAs, and circular RNAs, are related to the development, promotion, and metastasis of GI cancers, especially in angiogenesis. This review discusses the role of ncRNAs in mediating angiogenesis in various types of GI cancers and looks forward to the introduction of mimetics and antagonists as possible therapeutic agents.

Non-coding RNAs related to angiogenesis in gynecological cancer.

Gynecological cancer affects the female reproductive system, including ovarian, uterine, endometrial, cervical, vulvar, and vaginal tumors. Non-coding RNAs (ncRNAs), and in particular microRNAs, function as regulatory molecules, which can control gene expression in a post-transcriptional manner. Normal physiological processes like cellular proliferation, differentiation, and apoptosis, and pathological processes such as oncogenesis and metastasis are regulated by microRNAs. Numerous reports have shown a direct role of microRNAs in the modulation of angiogenesis in gynecological cancer, via targeting pro-angiogenic factors and signaling pathways. Understanding the molecular mechanism involved in the regulation of angiogenesis by microRNAs may lead to new treatment options. Recently the regulatory role of some long non-coding RNAs in gynecological cancer has also been explored, but the information on this function is more limited. The aim of this article is to explore the pathways responsible for angiogenesis, and to what extent ncRNAs may be employed as biomarkers or therapeutic targets in gynecological cancer.

Adolescent metabolic syndrome and its components associations with incidence of type 2 diabetes in early adulthood: Tehran lipid and glucose study.

AIM: To investigate the association of youth metabolic syndrome (MetS) and its components, individually and in combination with early adulthood incident type 2 diabetes (T2DM). METHODS: A total of 2798 adolescents aged 11-19 years enrolled in the study. At baseline, MetS, its components including blood pressure (BP), waist circumference (WC), triglycerides (TGs), fasting plasma glucose, and low HDL-C, and different combinations of MetS components were defined. After a mean 11.3 years of follow-up, T2DM was determined. Multivariable Cox proportional hazard regression analysis adjusted for age, sex, family history of T2DM, and adult BMI was used for data analysis. The hazard ratio (HR) and 95% confidence interval (CI) were reported. RESULTS: During the follow-up, 44 incidents T2DM were developed. Among different individual components, only high WC [HR = 2.63, 95% CI (1.39-4.97)] and high TGs [HR = 1.82, 95% CI (1.00-3.34)] remained as significant predictors only in the age and sex adjusted model. Regarding combinations of MetS components, 'high TGs and high WC' [HR = 2.70, 95% CI (1.27-5.77)], 'high BP and high WC' [HR = 2.52, 95% CI (1.00-6.33)], 'high TGs and high BP' [HR = 2.27, 95% CI (1.02-5.05)] as well as MetS per se [HR = 2.82, 95% CI (1.41-5.64)] had a significant relationship with incident T2DM in the multivariable adjusted model. Among different confounders, being female and having family history of T2DM were consistently associated with higher risk of T2DM, in different combinations of MetS components. CONCLUSIONS: Adolescence MetS and some combinations of MetS components predicted early adulthood T2DM. Thus, adolescents, particularly female ones, with combinations of MetS components as well as those with family history of T2DM could be targeted for lifestyle intervention.

Vitamin D and Non-coding RNAs: New Insights into the Regulation of Breast Cancer.

Breast cancer, a life-threatening serious disease with a high incident rate among women, is responsible for thousands of cancer-associated death worldwide. Numerous investigations have evaluated the possible mechanisms related to this malignancy. Among them, non-coding RNAs (ncRNAs), i.e., microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs have recently attracted attention of researchers. In addition to recent studies for evaluating the role of ncRNAs in breast cancer etiology, some investigations have revealed that vitamin D has regulatory and therapeutic roles in breast cancer. Moreover, an important link between vitamin D and ncRNAs in cancer therapy has been highlighted. Herein, the aim of this study was to discuss the available data on the mentioned link in breast cancer.

Circular RNA and Diabetes: Epigenetic Regulator with Diagnostic Role.

Circular RNAs, a group of endogenous non-coding RNAs, are characterized by covalently closed cyclic structures with no poly-adenylated tails. It has been recently recommended that cirRNAs have an essential role in regulating genes expression by functioning as a translational regulator, RNA binding protein sponge and microRNA sponge. Due to their close relation to the progression of various diseases such as diabetes, circRNAs have become a research hotspot. A number of circRNAs (i.e., circRNA_0054633, circHIPK3, circANKRD36, and circRNA11783-2) have been shown to be associated with initiation and progression of diabetes. Based on reports, in a tissue, some circRNAs are expressed in a developmental stage-specific manner. In this study, we reviewed research on circular RNAs involved in the pathogenesis and diagnosis of diabetes and their prognostic roles.

MicroRNA and exosome: Key players in rheumatoid arthritis.

Rheumatoid arthritis (RA) is known as one of important autoimmune disorders which can lead to joint pain and damage throughout body. Given that internal (ie, genetic and epigenetic alterations) and external factors (ie, lifestyle changes, age, hormones, smoking, stress, and obesity) involved in RA pathogenesis. Increasing evidence indicated that cellular and molecular alterations play critical roles in the initiation and progression of RA. Among various targets and molecular signaling pathways, microRNAs (miRNAs) and their regulatory networks have key roles in the RA pathogenesis. It has been showed that deregulation of many miRNAs involved in different stages of RA. Hence, identification of miRNAs and their signaling pathways in RA, could contribute to new knowledge which help to better treatment of patients with RA. Besides miRNAs, exosomes have been emerged as key messengers in RA pathogenesis. Exsosomes are nanocarriers which could be released from various cells and lead to changing of behaviors recipient cells via targeting their cargos (eg, proteins, messenger RNAs, miRNAs, long noncoding RNAs, DNAs). Here, we summarized several miRNAs involved in RA pathogenesis. Moreover, we highlighted the roles of exosomes in RA pathogenesis.

Determinants of taking dietary supplements in Iranian children and adolescents: the CASPIAN-V study.

AIM: Tendency for taking dietary supplements is dramatically increasing. However, limited studies exist in this regard. We aimed to assess the frequency and determinants of dietary supplement use among a nationally-representative sample of Iranian children and adolescents. METHODS: This population-based cross-sectional study (the CASPIAN V) was conducted in students aged 7 to 18 years old in 2015. Multistage, stratified cluster sampling method was used to select participants from thirty provinces in Iran. Data regarding taking vitamin and mineral supplements were collected. Demographic information, anthropometric indices, physical activity, screen time and body image were also evaluated. Multivariate logistic regression model was used for analyses. RESULTS: The prevalence of dietary supplements use was 34.1% and the most popular dietary supplement was Iron (12.9%). Multivariate logistic regression showed that boys (0.84, 95%CI: 0.78, 0.91) and body image perception (OR: 0.84, 95%CI: 0.75, 0.94) used less dietary supplements compared to others. Children aged 11 to 14 years (OR: 1.15, 95%CI: 1.06, 1.26) and those with moderate family socioeconomic status (OR: 1.12, 95%CI: 1.007, 1.25) used more supplement compared to other groups. Moreover, those with higher paternal educational level (OR: 0.77, 95%CI: 0.64, 0.93) used less supplements. However, living area, family size, paternal occupation, children BMI, Intended weight loss, and body image by student did not indicate any significant association. CONCLUSION: Our findings indicated that about one-third of Iranian children and adolescents used dietary supplements; iron supplements were the most frequent ones. Children aged 11 to 14 years, those with higher educated mothers and moderate family socioeconomic status used more supplements compared to others. However, boys, children with excess weight and those with high-educated parents used less supplements compared to others. More studies are needed to clarify the efficacy and safety of dietary supplements in different age groups in various societies.

Laser Thermal Ablation of Thyroid Benign Nodules.

Thermal ablation therapies for benign thyroid nodules have been introduced in recent years to avoid the complications of traditional methods such as surgery. Despite the little complications and the reportedly acceptable efficacy of thermal ablation methods, quite few medical centers have sought the potential benefits of employing them. This paper provides an introduction to the literature, principles and advances of Percutaneous Laser Ablation therapy of thyroid benign nodules, as well as a discussion on its efficacy, complications and future. Several clinical research papers evaluating the thermal effect of laser on the alleviation of thyroid nodules have been reviewed to illuminate the important points. The results of this research can help researchers to advance the approach and medical centers to decide on investing in these novel therapies.

Traumatic brain injury and adrenal insufficiency: morning cortisol and cosyntropin stimulation tests.

INTRODUCTION: Adrenal insufficiency (AI) has a great impact on the prognosis of patients with traumatic brain injury. There is a lack of consensus regarding the diagnostic criteria of AI. In these patients with acute stress we compared fasting cortisol, low and high dose cosyntropin stimulation tests to assess adrenal function in patients with moderate to severe traumatic brain injury. MATERIAL AND METHODS: This multicenter, cross-sectional study recruited 50 consecutive patients (aged between 15 and 70 years old) with moderate to severe traumatic brain injury who survived more than 5 days after the event. The patients' adrenal function was assessed using the fasting cortisol, 1 and 250-µg ACTH stimulation tests. RESULTS: More cases of AI were detected by the 1-µg ACTH stimulation test compared to those detected by the basal serum cortisol level and 250-µg ACTH stimulation test. The κ test showed no agreement between these tests. The incidence of AI in the first 10 days after traumatic brain injury varied from 34% to 82% according to the various definitions of AI. The incidence of hypotension and need for vasopressors was higher in the patients diagnosed by the 250-µg ACTH stimulation test (p < 0.0001). CONCLUSIONS: The incidence of secondary AI in moderate to severe traumatic brain injury seems to be high. A combination of stimulation test (either 250 or 1 µg) and basal cortisol level may improve diagnostic ability compared to either test alone. Hence performing both tests for the assessment of adrenal function in patients with traumatic brain injury is recommended.