A systematic review of dysregulated microRNAs in Hashimoto's thyroiditis.

BACKGROUND: Plenty of evidence suggests that dysregulated microRNAs are linked to developing autoimmune thyroid diseases. In this study, we aimed to identify commonly linked dysregulated microRNAs in Hashimoto's thyroiditis(HT) and explore microRNA-targeted genes and the involved pathways. METHODS: Embase, PubMed, Web of Science, and Scopus databases were searched using the MeSH terms and free text terms, which yielded 11879 articles published up to July 2023. Two-step screening(first for titles and second for abstracts) was completed according to inclusion and exclusion criteria. The search strategy was formulated using the PEO format(Population, Exposure, and Outcome) for observational studies. The corresponding target genes and relevant signaling pathways were also identified using web servers of Diana Tools/its mirPath v.3 software, miRNA Enrichment Analysis, Mirpath DB2, miRPathDB 2.0, and miRmap. RESULTS: Review inclusion criteria were met by 16 studies. Thirty-three microRNAs were identified as differentially expressed in HT patients compared to a healthy control after qRT-PCR or RNA sequencing confirmation. Only three miR-146a, miR-142, and miR-301 showed significant results in more than two studies comparing HT cases with healthy controls. CONCLUSION: Three key microRNAs in HT were identified by systematic review; the corresponding target genes and signaling pathways involved in the target genes were also identified. These microRNAs regulate the immune response and inflammation and may favor the development and progression of HT. These data may be beneficial to make a step forward to understand the exact etiology of HT and use of these MicroRNAs as possible diagnostic and prognostic biomarkers and as target therapy.

Alterations in CD4+ T Cell Cytokines Profile in Female Patients with Hashimoto's Thyroiditis Following Vitamin D Supplementation: A Double-blind, Randomized Clinical Trial.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors. METHODS: Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol [1, 25(OH)2D3] at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR. RESULTS: Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFß) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation. CONCLUSION: The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT. CLINICAL TRIAL REGISTRATION NUMBER: IRCT2016110130644N1.

RET/PTC rearrangement in papillary thyroid carcinoma arising in malignant struma ovarii with abdominal wall metastasis and cervical thyroid gland: a case report and review of the literature.

BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer. CASE PRESENTATION: We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis. CONCLUSIONS: In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Association of physical activity with increased PI3K and Akt mRNA levels in adipose tissues of obese and non-obese adults.

Phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway regulates glucose and lipid metabolism. We examined the association of PI3K and Akt expression in visceral (VAT) and subcutaneous adipose tissue (SAT) with daily physical activity (PA) in non-diabetic obese and non-obese adults. In this cross-sectional study, we included 105 obese (BMI ≥ 30 kg/m2) and 71 non-obese (BMI < 30 kg/m2) subjects (aged/ ≥ 18 years). PA was measured using a valid and reliable International Physical Activity Questionnaire(IPAQ)-long-form, and the metabolic equivalent of task(MET) was calculated. Real-time PCR was performed to analyze the mRNA relative expression. VAT PI3K expression had a lower level in obese compared to non-obese (P = 0.015), while its expression was higher in active individuals than inactive ones (P = 0.029). SAT PI3K expression was increased in active individuals compared to inactive ones (P = 0.031). There was a rise in VAT Akt expression in the actives compared to the inactive participants (P = 0.037) and in non-obese/active compared to non-obese/inactive individuals (P = 0.026). Obese individuals had a decreased expression level of SAT Akt compared to non-obsesses (P = 0.005). VAT PI3K was directly and significantly associated with PA in obsesses (ß = 1.457, P = 0.015). Positive association between PI3K and PA suggests beneficial effects of PA for obese individuals that can be partly described by PI3K/Akt pathway acceleration in adipose tissue.

Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

Longitudinal Associations Between TPO Gene Variants and Thyroid Peroxidase Antibody Seroconversion in a Population-Based Study: Tehran Thyroid Study.

Introduction: Autoimmune thyroid diseases (AITD) are usually accompanied by anti-thyroid antibodies which can serve as early predictive markers. This study was designed to investigate the relationship between thyroid peroxidase (TPO) gene variants and the presence of TPOAb and to evaluate the effect of environmental factors associated with seroconversion from TPOAb-negative to TPOAb-positive. Methods: Participants from phases 1 and 2 of the Tehran Thyroid Study in (n = 5327, ≥20 years) were evaluated in terms of TPOAb positivity, and its relationship with 53 single nucleotide polymorphisms (SNPs) from within the TPO gene (cross-sectional approach). TPOAb-negative participants (n = 4815) were followed up for seroconversion for 5.5 years. The relationship between the TPO gene variants and the TPOAb seroconversion was evaluated (longitudinal approach). Results: There were 521 TPOAb-positive participants in the cross-sectional phase and 266 new TPOAb-positive cases observed during the follow-up period. After quality control (Hardy-Weinberg equilibrium (p < 1 × 10-5) and minor allele frequency < 0.05), 49 SNPs were qualified for association analyses. From this set fourteen SNPs were identified that were associated with TPOAb positivity. rs6605278, located in the 3'UTR TPO gene, was the most highly significantly associated of the variant and remained associated after adjustment for age, gender, body mass index (BMI), smoking, number of parity, and oral contraceptive consumption in both cross-sectional and longitudinal analyses (p < 0.05). Conclusions: TPOAb-positivity can be partially explained by variants in the TPO gene. New TPOAb-associated SNPs were observed in Iranians as an ethnically diverse population.

Continued exposure to D-galactose in postnatal period may inhibit excessive primordial follicle reduction in rats exposed prenatally to D-galactose.

We aimed to compare the ovarian reserve of rats exposed to oral D-galactose during prenatal and early life with rats exposed to D-galactose only during the prenatal period. Fifteen female pregnant Wistar rats were randomly divided into three groups. The first and second groups were fed a D-galactose enriched diet (35%) from the third day of pregnancy to parturition (PP) and the third day to the end of lactation (PL), respectively. The control group (C group) was fed a standard diet. The study population was the female offspring of three groups (PP', PL', and C'), in which some reproductive factors were examined between 45 and 50 days of age. When compared with the PP' group, the number of primordial follicles was significantly higher in the PL' group at PND 45-50 (40 vs. 30; p = .01); however, the antimullerian hormone level was significantly reduced in the PL' group versus control group (-2.2, 95% confidence interval [CI]: -2.83, -1.53 ng/ml p = .000), and follicle-stimulating hormone level significantly increased in PP' group versus control (4.5 mIU/ml, 95% CI: 1.40-7.62, p = .005). There was no significant difference in leukocyte infiltration or antiovarian antibody among the groups. Continued exposure to D-galactose during the lactation period inhibits the primordial follicle loss in rats in terms of producing fewer atretic follicles.

Maternal Exposure to D-galactose Reduces Ovarian Reserve in Female Rat Offspring Later in Life.

Background: Embryonic life is critical for the formation of ovaries in mammals, and the intrauterine environment may affect ovarian reserve. Objectives: The present study aimed to investigate the impact of prenatal D-galactose exposure on ovarian reserve in female rat offspring in their later lives. Methods: Ten pregnant Wistar rats were randomly divided into two groups. In one group, rats were fed with 35% D-galactose-enriched food from the third day to the end of pregnancy, and in the other group, rats were fed with a standard diet throughout pregnancy. Female offspring (prenatally galactose-exposed rats and non-exposed control rats) were examined in terms of hormonal levels [anti-Mullerian hormones (AMH), follicle-stimulating hormone (FSH), and estradiol (E2)] and ovarian histology at 45 - 50, 105 - 110, and 180 - 185 days of their age. Results: The number of primordial follicles significantly decreased time-dependently in prenatally galactose-exposed rats compared to controls (P-value = 0.002). In addition, decreases in AMH (3.25 vs. 7.5 ng/mL; P = 0.000) and E2 (7.9 vs. 19.5 pg/mL; P = 0.000) and increases in FSH (6.5 vs. 0.8 mIU/mL; P < 0.007) were observed in galactose-exposed rats compared to controls at 45 - 50 days of age. Conclusions: Prenatal exposure to D-galactose negatively affects ovarian reserve in female rats in their later lives. However, further investigation is needed to confirm our findings and explore underlying mechanisms.

Association of miR-34a and miR-143 levels with PPARγ gene expression in adipose tissues of non-diabetic adults.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a promising therapeutic molecule. Epigenetic mechanisms, including non-coding RNAs, regulate the expression level of the PPARγ gene. OBJECTIVE: We aimed to examine the PPARγ expression in non-diabetic individuals in four body mass index (BMI) categories and its association with miR-34a and miR-143 expression. METHODS: Visceral and subcutaneous adipose tissues (VAT and SAT) samples were collected from patients undergoing bariatric or elective open abdominal surgeries. The subjects (mean age: 42±14.8 years) included 18 normal-weight, 19 overweight, 18 obese, and 19 morbidly obese individuals. The RNAs levels were determined by quantitative real-time PCR. RESULTS: The PPARγ expression was significantly upregulated in both adipose depots of the morbidly obese subjects compared to the normal group. SAT PPARγ level was significantly increased in the obese group compared to the normal-weight group (P<0.01); this increase was also significant in the SAT of morbidly obese subjects compared to the overweight cases (P=0.02). Differences in the regulation of PPARγ expression in both SAT and VAT were significant between the four groups (P<0.05). While miR-143 was overexpressed in the SAT of obese and morbidly obese individuals compared to the normal-weight group, the pairwise comparison showed no significant difference in the miR-34a expression of SAT between the four BMI groups (P>0.01). After controlling for the confounding factors, the expression of VAT PPARγ was directly associated with the miR-34a level in the normal-weight group (ß=0.311, P=0.010). A negative association was observed between the VAT PPARγ expression and miR-34a expression in obese cases (ß = - 0.594, P=0.039). CONCLUSION: The results also confirmed the regulatory function of microRNAs in the PPARγ expression and adipogenesis.

Clinical and Laboratory Characteristics of a Large Iranian Kindred Afflicted with Von Hippel Lindau Disease.

BACKGROUND: Von Hippel Lindau (VHL) disease is a hereditary disorder characterized by the development of benign or malignant tumors in the brain, spinal cord, eyes, adrenal medulla, kidney, pancreas, and many other organs. Advances in molecular diagnosis have led to the identification of the affected members of families at earlier stages. We present the clinical, laboratory, and genetic characteristics of five generations of a large Iranian kindred with VHL. METHODS: The proband, a 52-year-old Iranian man, was recognized with VHL. All family members underwent clinical, laboratory, imaging, and genetic evaluation. Medical files and histopathology reports of patients who had been operated on before were also reviewed. Diagnosis of the disease was based on clinical findings, positive family history of VHL, and development of a central nervous system or retinal hemangioblastoma or pheochromocytoma. RESULTS: Based on diagnostic criteria, our initial evaluations revealed that 10 members of the family had already been affected by the disease. Among them, nine had pheochromocytoma, and one had retinal hemangioblastoma. There was no case of kidney tumors among the kindred. CONCLUSIONS: Study results show the high penetrance of the disease and focus on the large burden imposed by the disease on the health and quality of life of patients afflicted with the disease, emphasizing the importance of surveillance from early childhood for detection and management of the disease as early as possible.

Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient's cells. In this paper we examine the results of an investigational assessment of secukinumab gene therapy. MATERIALS AND METHODS: In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the approved secukinumab as the standard reference. RESULTS: Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene therapies. CONCLUSION: In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases.

Induced premature ovarian insufficiency by using D galactose and its effects on reproductive profiles in small laboratory animals: a systematic review.

BACKGROUND: Development of a hyper-gonadotropic hypoestrogenism condition in women < 40 years, defined as premature ovarian insufficiency (POI), is the most common long-term complication in female survivors of galactosemia. In this systematic review, summarize the galactose (GAL) induced POI in rat and mice models. METHODS: For this systematic review, we conducted a search of case control studies published from 1990 until August 2018 in PubMed/Medline, and Web of science, using the descriptors in the title/abstract field. A 'pearl growing' strategy was employed whereby, after obtaining the full text articles, reference lists of all included studies (n = 14) were reviewed for additional publications that could be used. RESULTS: We selected and categorized 14 studies according to the time of exposure to GAL into two groups of prenatal (n = 4) and postnatal (n = 10). Findings of these studies showed that the different stages of follicular development are targeted differently by galactose exposure during the prenatal and postnatal periods: The small follicles (primordial and primary follicles) are targeted by galactose toxicity during prenatal exposure and the pre-antral and antral follicles are targeted by galactose toxicity during postnatal exposure. CONCLUSIONS: This systematic review shows that galactose has an ovotoxicity effect that can be used to induce appropriate POI animal models only if sufficient doses, proper onset time, and duration of prenatal exposure are taken into account. An optimized model of POI induction should manifest all the required ovarian morphological, hormonal, and estrus cycle changes.

The Principles of Biomedical Scientific Writing: Discussion.

The discussion section of a scientific paper is supposed to interpret and elucidate the significance of the study findings, highlight current knowledge available on the research problem being investigated, and explain the novel aspects emerging from the findings of the study in moving the field forward. A well-written discussion should provide clear "statements of the main findings", "possible explanations and implications", "strengths and weaknesses of the study and other studies", "unanswered questions", and "suggestions for future research". The authors also need to clarify the external validity of the findings and show how the findings can be generalized. In this review, we focus on the function, content, and organization of the "discussion section" of a hypothesis-testing paper. Beyond providing the most important principles and common strategies for organizing the discussion section, we also discuss metadiscourse, scientific explanation (reasoning and contextualization), and models of scientific explanation.

The Principles of Biomedical Scientific Writing: Results.

The "results section" of a scientific paper provides the results related to all measurements and outcomes that have been posted earlier in the materials and methods section. This section consists of text, figures, and tables presenting detailed data and facts without interpretation and discussion. Results may be presented in chronological order, general to specific order, most to least important order, or may be organized according to the topic/study groups or experiment/measured parameters. The primary content of this section includes the most relevant results that correspond to the central question stated in the introduction section, whether they support the hypothesis or not. Findings related to secondary outcomes and subgroup analyses may be reported in this section. All results should be presented in a clear, concise, and sensible manner. In this review, we discuss the function, content, and organization of the "results section," as well as the principles and the most common tips for the writing of this section.

BRAF V600E mutation and microRNAs are helpful in distinguishing papillary thyroid malignant lesions: Tissues and fine needle aspiration cytology cases.

AIMS: Mutations of BRAF oncogene are considered to contribute in the invasiveness and poor clinicopathologic features of papillary thyroid cancer (PTC). As a step towards understanding the underlying molecular mechanisms of this contribution, we aimed to examine the association of four microRNAs' (miR-222, -137, -214, -181b) levels with BRAFV600E and clinicopathological features in PTC tissues and fine needle aspiration (FNA) specimens. METHODS: In total, 56 PTC and 27 benign with multinodular goiter tissue samples, 95 FNA samples, and B-CPAP and HEK293 cell lines were examined. BRAFV600E mutation was examined in PTC tissues and FNA samples. Expression of microRNAs was assessed by real-time quantitative reverse transcription-PCR. KEY FINDINGS: The frequency of BRAFV600E in PTC tissues and FNA samples "suspicious for PTC" was 41.1 and 36.8%, respectively. MiR-222, -137, -214, and -181b were significantly upregulated in PTC tumors (P < 0.05) and in B-CPAP cell line (P < 0.001). In FNA, the expressions of miR-222, -181b and -214 were significantly elevated in patients suspected for PTC (P < 0.05), while there was no significant difference in miR-137. After adjustment for age and sex, miR-181b was associated with an increased risk of bearing BRAFV600E mutation (OR: 1.27; 95% CI: 1.01-1.61; P = 0.045) and risk of lymphovascular invasion (OR: 1.66; 95% CI: 1.01-2.72; P = 0.045); miR-137 was associated with the risk of larger tumor size (OR: 1.31; 95% CI: 1.04-1.65; P = 0.022); miR-222 was related to increase in extracapsular invasion (OR: 1.28; 95% CI: 1.04-1.57; P = 0.018). SIGNIFICANCE: Upregulation of miR-222, -214 and -181b has been confirmed in PTC tumors, FNA samples and cell line. MiR-137 upregulation has been confirmed in PTC tumors and cell line, but not in FNA samples. MiR-222, -137 and -181b showed an association with the degree of malignancy in PTC tumors.

The Principles of Biomedical Scientific Writing: Materials and Methods.

The materials and methods (M&M) section is the heart of a scientific paper and is subject to initial screening of the editor to decide whether the manuscript should be sent for external review. If the M&M section of a scientific paper be considered as a recipe, its ingredients would be who, what, when, where, how, and why. M&M should effectively respond to the study question/hypothesis using the following basic elements including materials, study design, study population/subjects or animals, methods of measurements/assessments, and statistical analysis. A well-organized M&M permits other scientists to evaluate the study findings and repeat the experiments. Although there are several disciplinary differences in the M&M, similar dos and don'ts may be considered to organize a well-written M&M. Briefly, authors need to provide clear-cut, adequate, and detailed information in the M&M section. In this review, the structure, the principles, and the most common recommendations for writing the M&M section are provided, both in general and study-specific; these could help authors effectively prepare the M&M section of a scientific biomedical manuscript.

Genetic Identification for Non-Communicable Disease: Findings from 20 Years of the Tehran Lipid and Glucose Study.

CONTEXT: Tehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects. EVIDENCE ACQUISITION: For all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH). RESULTS: This review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5). CONCLUSION: Considering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics' data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.

Outcomes of a Longitudinal Population-based Cohort Study and Pragmatic Community Trial: Findings from 20 Years of the Tehran Lipid and Glucose Study.

CONTEXT: The Tehran lipid and glucose study (TLGS) is one of the oldest population-based longitudinal cohort studies, providing knowledge about the incidence and risk factors of some non-communicable diseases (NCDs) in West Asia which hitherto was relatively scarce. We reviewed the methods and results related to the outcome measurements of this study. EVIDENCE ACQUISITION: We reviewed all the TLGS papers which reported the incidence of NCDs. RESULTS: The TLGS was initiated in 1999 - 2001 on a population in district no. 13 of Tehran with the same age distribution of the overall Tehran population and with a middle socioeconomic status. Totally, 15005 individuals, aged ≥ 3 years, participated in the first examination; reexaminations were conducted in a triennial manner and 3550 individuals were added in the second examination. All participants were also followed up annually and asked about any medical event leading to hospitalization or death. A part of participants was assigned to an educational program for lifestyle modification. High incidence of cardiovascular disease (CVD), premature CVD, diabetes and hypertension (around 19, 6, 10 and 31 in men and 11, 5, 11 and 29 in women per 1000 person-year, respectively) besides the high incidence of pre-diabetes and pre-hypertension (around 46 and 76 in men and 37 and 49 in women per 1000 person-year, respectively) showed a worrying situation. Fortunately, the results of the community interventions were promising with around 20% reduction in the risk of metabolic syndrome up to six years. CONCLUSIONS: These precise detections of different outcomes in the TLGS provided valuable evidences for prediction and prevention of NCDs in Iran with some novelties in the middle-income countries in the world. The Tehran thyroid study (TTS) and the Tehran cardiometabolic genetic study (TCGS), conducted in the framework of the TLGS, are among few studies aiming to determine the natural course of thyroid function and to identify patterns of genetic polymorphisms related to cardiometabolic outcomes, respectively.

Review of Rationale, Design, and Initial Findings: Tehran Lipid and Glucose Study.

In the late 1990s the non-communicable diseases were becoming increasingly more prevalent and a significant proportion of evidence in this regard had originated from industrialized "Western" countries. This had led to a landscape where most national and local health decisions regarding non-communicable diseases (NCDs) were informed by data generated elsewhere. Iran, as a large country in the Middle East was no exception and was going through significant population growth and urban development at the time. An initiative by the Iranian National Scientific Research Council funded an idea that was aimed at delineating the local epidemiology of NCDs and their risk factors in a manner that was unprecedented. The result was Tehran Lipid and Glucose Study (TLGS), the first and longest running cohort of its sort in Iran. Initial data out of TLGS reported the characteristics of 15005 people aged over 3 years in a representative population of Tehranians. Additionally, distribution and prevalence of cardiovascular risk factors among the study population were characterized. This population was selected through a multistage stratified cluster random sampling technique from the population of district 13 in Tehran. In addition, TLGS gave rise to a great deal of important and highly effective initial findings on national cut-off points for various variables, information about nutrition, hypertension, dyslipoproteinemia, and metabolic syndrome. TLGS also generated information about metabolic health indicators among children and adolescents. Here we present a brief overview of rationale, design, and initial findings of TLGS.

Contributions and Implications of the Tehran Lipid and Glucose Study.

Tehran Lipid and Glucose Study (TLGS), an epidemiological study of non-communicable disease with 20 years follow up in a developing country in nutrition transition is a unique study in 15000 family based individuals, 3 - 75 years of age in a part of large city of Tehran. The success rate of recruitment for 20 years, intervention for lifestyle change, and thyroid, reproduction and cardiometabolic genetic studies derived from TLGS have paved suitable path towards precision medicine. In this review, baseline findings and changes of risk factors for the development of NCD including body weight, nutrition, physical activity, blood pressure, tobacco smoking, serum glucose and serum lipids as well as metabolic syndrome, chronic kidney disease, quality of life and biochemical findings in TLGS cohort have been summarized. The results of community based intervention for lifestyle change caused decreases in the prevalence of metabolic syndrome and the incidence of diabetes. It is concluded that TLGS has served as a model for other cohort studies in Iran and the region; it has helped to mobilize scientists in developing countries; it has established locally needed definitions of NCD variables; has served as a model for cohort studies in developing countries in nutrition transition with all socioeconomic constraints and has helped manpower education and development of local CVD risk scores for implementation of NCD management.