Genetic variations in IKZF3, LET7-a2, and CDKN2B-AS1: Exploring associations with metabolic syndrome susceptibility and clinical manifestations.

BACKGROUND AND AIM: Metabolic syndrome (MetS) increases the risk of atherosclerosis and diabetes, but there are no approved predictive markers. This study assessed the role of specific genetic variations in MetS susceptibility and their impact on clinical manifestations. METHOD: In this study, a genotype-phenotype assessment was performed for IKZF3 (rs907091), microRNA-let-7a-2 (rs1143770), and lncRNA-CDKN2B-AS1 (rs1333045). RESULTS: Analyses indicate that while rs907091 and rs1143770 may have potential associations with MetS susceptibility and an increased risk of atherosclerosis and diabetes, there is an observed trend suggesting that the rs1333045 CC genotype may be associated with a decreased risk of MetS. The genotypes and allele frequencies of rs1333045 were significantly different between studied groups (OR = 0.56, 95% CI 0.38-0.81, p = 0.002, and OR = 0.71, 95% CI 0.55-0.92, p = 0.008), with the CC genotype displaying increased levels of HDL. Furthermore, the rs907091 TT genotype was associated with increased triglyceride, cholesterol, and HOMA index in MetS patients. Subjects with the CC genotype for rs1143770 had higher HbA1c and BMI. In silico analyses illustrated that rs907091 C remarkably influences the secondary structure and the target site of a broad spectrum of microRNAs, especially hsa-miR-4497. Moreover, rs1333045 creates a binding site for seven different microRNAs. CONCLUSION: Further studies on other populations may help confirm these SNPs as useful predictive markers in assessing the MetS risk.

The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been the world's driving fatal bacterial contagious disease globally. It continues a public health emergency, and around one-third of the global community has been affected by latent TB infection (LTBI). This is mostly due to the difficulty in diagnosing and treating patients with TB and LTBI. Exosomes are nanovesicles (40-100 nm) released from different cell types, containing proteins, lipids, mRNA, and miRNA, and they allow the transfer of one's cargo to other cells. The functional and diagnostic potential of exosomal miRNAs has been demonstrated in bacterial infections, including TB. Besides, it has been recognized that cells infected by intracellular pathogens such as Mtb can be secreting an exosome, which is implicated in the infection's fate. Exosomes, therefore, open a unique viewpoint on the investigative process of TB pathogenicity. This study explores the possible function of exosomal miRNAs as a diagnostic biomarker. Moreover, we include the latest data on the pathogenic and therapeutic role of exosomal miRNAs in TB.

Relationship between dietary macronutrient composition and non-alcoholic fatty liver disease in lean and non-lean populations: a cross-sectional study.

OBJECTIVE: The current study aimed to customize dietary changes for lean patients with non-alcoholic fatty liver disease (NAFLD). DESIGN: The current study was done with a population-based cross-sectional design. The FFQ was used to analyse dietary macronutrient intake and ultrasonography results for NAFLD diagnosis. The study subjects were divided into the lean and non-lean groups based on their BMI (< 25 and ≥ 25). Multivariable logistic regression was used to evaluate the relationship between dietary macronutrients and NAFLD. Substitution analyses were also performed. SETTING: Amol and its suburban areas in Iran. PARTICIPANTS: Adults in the age range of 18 to < 65 with full relevant data. RESULTS: Among the total study subjects (2308), 46·7 % had fatty liver. The substitution of polysaccharides for animal protein and SFA in the lean group resulted in a significant NAFLD reduction, whereas the substitution of SFA for all types of macronutrients, except for n-6 and mono-disaccharides, led to a significant increase in NAFLD (P < 0·05). In non-lean participants, the substitution of MUFA for mono-disaccharides resulted in a significant reduction of NAFLD (P < 0·05). In this group, the substitution of SFA and mono-disaccharides for MUFA, and n-6 for all macronutrients, except vegetable protein and SFA, were significantly related to an increase in NAFLD (P < 0·05). CONCLUSIONS: Lower lean NAFLD is correlated with increasing polysaccharides in exchange for SFA and animal protein intake, whereas lower non-lean NAFLD is correlated with increasing MUFA in exchange for mono-disaccharides and reducing n-6 and SFA.

Clinical Manifestations of Gastrointestinal Symptoms in COVID-19 Patients: An Integrative Review.

After the outbreak of novel coronavirus disease 2019 (COVID-19) in Wuhan, China, its spread to other countries is rapidly increasing. In this integrative review, we report the prevalence of gastrointestinal symptoms in patients with COVID-19. For this purpose, available articles on gastrointestinal manifestations in patients with COVID-19, which were reported from China, were reviewed. All reviewed articles were searched from December 11, 2019, to June 20, 2020, based on specific key words. Related findings in these articles show that the main target of COVID-19 is lung tissue, as after the virus enters the body, it mainly causes respiratory symptoms in affected patients. But in addition to respiratory symptoms, it is possible that, over time, these patients present with other symptoms, the most obvious of which are gastrointestinal symptoms. It is well documented that diarrhea and vomiting are the most common gastrointestinal symptoms in COVID-19 patients. As part of this report, we also look at the incidence and frequency of gastrointestinal symptoms in COVID-19 patients in Iran. The results can be used by providers as a guideline for better management of gastrointestinal symptoms in these patients.

Serum level of Vitamin D is associated with COVID-19 mortality rate in hospitalized patients.

BACKGROUND: Due to widespread of coronavirus disease 2019 (COVID-19) infection, identification of its risk factors and clinical characteristics are important. The aim of the present study was to assess Vitamin D levels in individuals with severe acute respiratory syndrome coronavirus-19 infection and to report on its potential as a predictive marker. MATERIALS AND METHODS: All patients, diagnosed with COVID-19 infection from February 16 to March 21, 2020, and referred to Firoozgar Hospital, Tehran, Iran, were enrolled in this study. Vitamin D analysis was undertaken on patient serum samples using a commercial kit (Pars Azmoon Co., Tehran, Iran). SPSS v. 22 was used for statistical analysis. RESULTS: Vitamin D serum concentration was analyzed in a total of 317 patients whose mean age ± standard deviation was 62.05 ± 15 years and with 62.5% being male. A significant association of Vitamin D level and death was observed. Higher levels of serum Vitamin D had protection against death (odds ratio = 0.955 [95% confidence interval = 0.923-0.988], P = 0.008). CONCLUSION: As a preliminary study in the Iranian population who suffered COVID-19 disease, we identified that Vitamin D deficiency was associated with a higher death rate and intensive care unit admission.

Cutaneous hemorrhagic bullae in a patient with COVID-19: A case report.

COVID-19 was first discovered in Wuhan, China, and has spread rapidly around the world. The most important manifestation of COVID-19 was ARDS-like lung injury at first, but the involvement of other organs, such as kidney, heart, liver, and skin, was gradually reported. It is important to report and share all atypical manifestations of this disease to help other physicians to gain more knowledge about this new viral disease. As mentioned, there are also studies that show different types of cutaneous involvement in these patients, but due to the lack of more detailed studies in this field, and on the other hand, the possible usefulness of skin lesions as a diagnostic or alarming sign in the COVID-19 era, in this study we report a COVID-19 patient with a large hemorrhagic blister similar to sepsis-induced skin lesion. Despite the lack of common symptoms of the disease, the lung scan of the patient was positive for COVID-19.

Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) at baseline of treatment in thalassemia patients: a referral center study.

Patients with thalassemia major are at high risk of hepatitis C through blood transfusion from donors infected by hepatitis C virus (HCV). The use of direct-acting antiviral (DAA) therapy against such HCV infections has increased in different populations. However, resistant viral variants can affect treatment outcomes, and therefore improved surveillance strategies are needed. Accordingly, we aimed to evaluate resistance-associated substitutions (RASs) to HCV DAAs at the baseline of treatment in thalassemia patients in a referral center. Out of 89 thalassemia patients who suffered from HCV infection and were referred to our center between 2016 and 2017, 43 underwent further analysis of the HCV nonstructural proteins NS5A and NS5B using polymerase chain reaction (PCR) sequencing methods. Unique primers were designed using bioinformatics software for separate detection of HCV subtypes 1a, 3a, and 1b. Detection of RASs was performed based on previously published literature. Statistical analysis was carried out using SPSS version 19. The participants, 60.4% (26/43) of whom were male, had a mean age ± standard deviation (SD) of 33.0 ± 5.0 years. HCV subtype 1a was found in 27 cases, 3a in 13, and 1b in three. In HCV subtype 1a there were 163 mutations in NS5A and 212 mutations in NS5B. The frequency of RASs was 20.9% (8 RASs in 9 patients), including M28V and H58P in subtype 1a, L28M, R30Q, C316N, and C316S in subtype 1b, and S24F in subtype 3a. Statistically, the subtype 1b and a higher mutation rate in NS5A were associated with RASs (p-value < 0.05). The emergence of natural RASs to HCV DAAs serves as a warning of the risk of drug resistance in response to the broad usage of antivirals. However, relapses in these DAA-treated HCV-infected thalassemia patients are rarely reported. Our findings indicate that the prevalence of RASs prevalence at baseline was 20.9% in these patients, and this calls for extrapolation to a larger population study, as highlighted in other studies, with larger sample sizes, high-throughput methods, and follow-up in order to fully evaluate treatment outcomes in RASs-detected individuals. Optimized therapeutic strategies, particularly in complex, difficult-to-cure patients, can effectively prevent DAA treatment failure as a result of selection for RASs.

Erythrocyte membrane fatty acid profile & serum cytokine levels in patients with non-alcoholic fatty liver disease.

Background & objectives: Fatty acids may affect the expression of genes, and this process is influenced by sex hormones. Cytokines are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so this study was aimed to assess the association of erythrocyte membrane fatty acids with three cytokines and markers of hepatic injury in NAFLD patients and to explore whether these associations were the same in both sexes. Methods: In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD during the study period. Tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), aspartate aminotransferase and alanine aminotransferase were measured in a fasting serum sample, and Fibroscan was conducted for each individual. Gas chromatography was used to measure erythrocyte membrane fatty acids. Univariate and multiple linear regressions were used to analyze data. Results: In men, IL-6 had a significant (P <0.05) positive association with total ω-3 polyunsaturated fatty acids (PUFAs). In women, TNF-α had a significant positive association with total ω-3 (P <0.05) and ω-6 (P <0.01) PUFAs, IL-6 had a significant (P <0.05) positive association with total monounsaturated fatty acids and MCP-1 had a significant positive association with total trans-fatty acids (P <0.05). No significant associations were observed between erythrocyte membrane fatty acids and liver enzymes or Fibroscan report in both sexes. In this study, women were significantly older than men [51 (42.75-55) vs 35.5 (29-52), P <0.01], so the associations were adjusted for age and other confounders. Interpretation & conclusions: Erythrocyte membrane fatty acid profile was not associated with serum liver enzymes or Fibroscan reports in NAFLD patients, but it had significant associations with serum TNF-α, IL-6 and MCP-1 and these associations were probably sex dependent.

Metabolic Syndrome Is Associated with Health-Related Quality of Life in Suspected Patients with Nonalcoholic Steatohepatitis.

OBJECTIVE: This study was designed to examine the effect of metabolic syndrome (MetS) on health-related quality of life (HRQOL) in patients with suspected nonalcoholic steatohepatitis (NASH). SUBJECTS AND METHODS: Three hundred thirty-two patients (236 males and 96 females) with suspected NASH from the Amol cohort study were included in this study. MetS was diagnosed based on Adult Treatment Panel III criteria and HRQOL was measured using the 12-Item Short-Form Health Survey (SF-12) questionnaire (with 8 subscales and 2 summary components). A multivariable linear regression model was used to assess the independent effect of MetS on HRQOL. RESULTS: The mean age of the study population was 42 ± 13 years (range 18-82). The prevalence of MetS was 43.4% (n = 144) and the mean scores on the Physical Component Summary (PCS) and the Mental Component Summary were 72.4 ± 20.86 and 42.7 ± 12.42, respectively. The multivariable linear regression model showed that MetS was negatively associated with 4 subscales of HRQOL that included: role limitations due to physical problems (RP) (B = -14.05, p = 0.004), bodily pain (BP) (B = -7.37, p = 0.02), vitality (VT) (B = -7.72, p = 0.022), and role limitations due to emotional problems (RE) (B = -12.67, p = 0.005) after adjustment for other variables. Also, MetS had a borderline association with the general health and mental health subscales and the PCS (p < 0.1). CONCLUSION: In this study, there was a strong association between MetS and 4 subscales (RP, BP, VT, and RE) of HRQOL in patients with suspected NASH; this could be considered as a part of health policy to improve general health.

Identifying the pattern of unhealthy dietary habits among an Iranian population: A latent class analysis.

Background: An unhealthy diet is one of the most important risk factors for chronic diseases. The goal of this study was to use the latent class analysis (LCA) modeling to define unhealthy diet habits among an Iranian population. Methods: This cross-sectional study was conducted within the framework of Amol (North of Iran) cohort health study (Phase 1). The participants aged 10 to 90 years. All participants provided written informed consent. Latent class analysis was used to classify the participants of the study. All analyses were conducted by PROC LCA in SAS 9.2 software. Significance level was set at 0.05. Results: The mean age of the participants was 42.58±17.23 years. Four classes of individuals with different diet habits were identified using LCA modeling: class 1: individuals with healthy diet patterns (92.6%); class 2: individuals with slightly unhealthy diet habits (6.3%); class 3: individuals with relatively unhealthy diet habits (0.8%); and class 4: individuals with unhealthy diet habits (0.2%). Being female and alcohol consumption increased the odds of membership in latent classes 2,3, and 4 compared to class 1. Physical activity decreased the odds of membership in classes 3 and 4 compared to class 1. Conclusion: Overall, almost more than 7.4% of all participants had some degree of unhealthy dietary habits, and some variables acted as risk factors for membership in risky classes. Therefore, focusing on these variables may help design and execute effective preventive interventions in groups with unhealthy dietary habits.

Pattern of body mass index, chronic diseases, and physical component of quality of life in a population in North of Iran: A latent class analysis.

Background: Due to the rise of non-communicable diseases (NCDs) and lifestyle changes, this study aimed at determining the subclasses of Iranian adults based on body mass index, some NCDs, and status of physical component of quality of life. Methods: A total of 5207 participants of Amol cohort study were studied in this study. Latent class analysis (LCA) was used to determine the best model with the minimum AIC or BIC. Results: We decided that the 6 latent classes model was the best model. The first class described 35.1% of the participants and was characterized by individuals with no disease status. The sixth class described 0.7% of the individuals and was characterized by individuals exhibiting high probability of body mass index (BMI) equal or more than 25, kidney inadequacy, hypertension, and moderate physical component of quality of life status. Conclusion: This study showed the pattern of body mass index, chronic diseases, and physical component of quality of life. Our findings demonstrated that some risk factors and non-communicable diseases tend to accumulate in some classes, especially classes 5 and 6, and thus the risk of developing these diseases rises along with increase in their clustering abilities. These results point out the critical importance of designing specific preventive interventional programs for these stratums of individuals.

Association between Nicotinamide Phosphoribosyltransferase and de novo Lipogenesis in Nonalcoholic Fatty Liver Disease.

OBJECTIVE: This study explored the association between serum nicotinamide phosphoribosyltransferase (NAMPT) and hepatic de novo lipogenesis (DNL) in nonalcoholic fatty liver disease (NAFLD) and determined whether or not this association is sex dependent. SUBJECTS AND METHODS: In this cross-sectional study, 62 consecutive patients (32 males, 30 females) with NAFLD were recruited. Serum NAMPT (by ELISA), palmitic acid, and the DNL index of erythrocyte membranes as markers of hepatic DNL (by gas chromatography) were analyzed. The controlled attenuation parameter (CAP) and body impedance analyzer were used to assess hepatic and body fat, respectively. Univariate and multiple linear regressions (to adjust for confounders) were used to analyze the association of serum NAMPT with palmitic acid, DNL index, CAP, and body fat. RESULTS: The respective values of serum NAMPT (2.44 ± 1.03 vs. 2.45 ± 1.13 ng/mL, p = 0.98), DNL index (3.11 [2.60-3.71] vs. 3.05 [2.40-3.59], p = 0.90), and palmitic acid (20.55% [15.34-24.04] vs. 22.64% [21.15-25.95], p = 0.07) were not significantly different between men and women, but those of CAP (326 [300-340] vs. 300 [261.25-329], p = 0.002) and body fat (37.71 ± 3.80 vs. 26.60 ± 5.70, p < 0.001) were significantly higher in women. In women, serum NAMPT had a significant negative association with the DNL index (ß = -0.56, p = 0.01). The DNL index also had a significant negative association with body fat (ß = -0.46, p = 0.02). In men, the only significant association was the positive association between serum NAMPT and CAP (ß = 0.35, p = 0.035). CONCLUSION: Higher serum NAMPT in women was associated with a lower hepatic DNL index, while in men it was associated with higher hepatic fat and had no association with the DNL index. Therefore, the serum NAMPT level interpretation for NAFLD prognosis is probably sex dependent.

Investigation of FIH-1 and SOCS3 expression in KRAS mutant and wild-type patients with colorectal cancer.

Colorectal cancer (CRC) is a multistep process based on the accumulation of somatic mutations in genes such as APC and KRAS. Data on the presence of mutations in KRAS gene in CRC and its relationship with clinicopathological parameters and expression of genes involved in tumor progression are scarce. We unbiasedly examined the KRAS status in samples from 99 patients and its correlation with clinicopathological parameters such as age, sex, tumor location, lymph node metastasis, tumor stage, tumor grade, and vascular invasion. Consistent with reports of other researchers, 38.4 % of our samples harbored KRAS mutation in their genomes with preferential mutation in codon 12 (89.4 %). Nevertheless, unlike previous reports, we were not able to correlate KRAS status with clinicopathological parameters (P > 0.05) except for vascular invasion. Patients with KRAS mutation have more vascular invasion compared with patient having wild-type KRAS. Next, we investigated the expression of two tumor suppressor genes, factor-inhibiting hypoxia-inducible factor 1 (FIH-1) and suppressor of cytokine signaling (SOCS3), in both KRAS mutant and wild-type groups and looked for any correlation between their expression and clinicopathological parameters. Although the expression of both genes was not regular, none of the clinicopathological parameters were associated with the expressions of FIH-1 and SOCS3 at mRNA level (P > 0.05). However, decline in FIH-1 expression at protein level in KRAS mutant group was correlated with stage IV and grade 2 of tumor (P ≤ 0.05). Our results demonstrated that there is no or low correlation between KRAS status, FIH-1, and SOCS3 expression with epidemiologic and clinicpathological characteristics in CRC.

Utility of endoscopic ultrasound to diagnose remnant stones in symptomatic patients after cholecystectomy.

BACKGROUND AND STUDY AIMS: Stones in the cystic duct stump (CDS) or gallbladder remnant after cholecystectomy are difficult to identify. The aim of this study was to evaluate the utility of endoscopic ultrasound (EUS) in the diagnosis of stones in the CDS or gallbladder remnant in patients with postcholecystectomy syndrome. METHODS: A prospective study was conducted between January 2011 and December 2012 in consecutive patients with pancreaticobiliary-type pain or acute pancreatitis (n = 112) following cholecystectomy. Diagnostic modalities including EUS were used to diagnose the cause of postcholecystectomy syndrome. RESULTS: A total of 11 patients (10 %) were found to have stones in the gallbladder remnant (n = 8), CDS (n = 2), or both (n = 1). In eight patients, EUS was the first imaging procedure to make the diagnosis. Seven patients agreed to undergo repeat surgery, and six of them remained free of symptoms postoperatively after a median follow-up period of 4 months (range 1 - 13 months). CONCLUSION: EUS may be an important procedure to consider in the study of patients with symptoms after cholecystectomy, as the diagnosis of residual stones is frequently missed by other imaging modalities.

Effects of synbiotic supplementation on insulin resistance in subjects with the metabolic syndrome: a randomised, double-blind, placebo-controlled pilot study.

To evaluate the effects of synbiotic supplementation on insulin resistance and lipid profile in individuals with the metabolic syndrome, we conducted a randomised, double-blind, placebo-controlled pilot study on thirty-eight subjects with the metabolic syndrome; they were supplemented with either synbiotic capsules containing 200 million of seven strains of friendly bacteria plus fructo-oligosaccharide or placebo capsules twice a day for 28 weeks. Both the synbiotic (G1) and the placebo (G2) groups were advised to follow an energy-balanced diet and physical activity recommendations. Parameters related to the metabolic syndrome and insulin resistance were measured every 7 weeks during the course of the study. After 28 weeks of treatment, the levels of fasting blood sugar and insulin resistance improved significantly in the G1 group (P< 0·001). Both the G1 and G2 groups exhibited significant reductions in TAG levels ( - 71·22 v. - 10·47 mg/dl ( - 0·80 v. - 0·12 mmol/l) respectively; P< 0·001) and total cholesterol levels ( - 21·93 v. - 14·2 mg/dl ( - 0·57 v. - 0·37 mmol/l) respectively; P= 0·01), as well as increases in HDL levels (+7·7 v. +0·05 mg/dl (+0·20 v. +>0·01 mmol/l) respectively; P< 0·001). The mean differences observed were greater in the G1 group. No significant changes were observed in LDL levels, waist circumference, BMI, metabolic equivalent of task and energy intake between the groups. The present results indicate that synbiotic supplementation increases the efficacy of diet therapy in the management of the metabolic syndrome and insulin resistance.

The association between dietary inflammatory index (DII) scores and c-reactive protein (CRP) and nonalcoholic fatty liver disease (NAFLD) in a general population cohort.

BACKGROUND AND AIMS: Although there is extensive literature showing the ability of the dietary inflammation index (DII®) to predict concentrations of plasma inflammatory markers, few studies are testing the association between DII scores and nonalcoholic fatty liver disease (NAFLD). Considering the high prevalence of NAFLD and its complications, we conducted a validation study of DII scores and examined its association with NAFLD in the general adult population of Iran. METHODS: This cross-sectional study was conducted on 3110 adult participants in the Amol Cohort Study (AmolCS) who underwent abdominal ultrasonography to diagnose NAFLD. DII and energy-adjusted DII (E-DII™) scores were computed using data from a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Multivariable logistic regression adjusting for socio-demographic, lifestyle, and health-related factors was used to assess association. RESULTS: The EDII was associated with CRP inflammatory biomarker. Participants in the highest, i.e., most pro-inflammatory tertile had the highest odds of NAFLD by ultrasound in all models [fully adjusted model: OR (95 % CI) tertile3vs.1:1.54 (1.05-2.05); Ptrend = 0.04, and 1.63 (1.19-2.21); Ptrend = 0.03 in women and men, respectively]. The highest tertile had the highest OR for NAFLD by fatty liver index (FLI) only in men [fully adjusted model OR (95 % CI) tertile3vs.1: 1.77 (1.15-2.71); Ptrend = 0.01]. Similar results were also obtained for NAFLD by hepatic steatosis index (HSI) in women [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.70 (1.12-2.58); Ptrend = 0.03]. The results of the fully adjusted multivariable model of liver markers and NAFLD status, stratified by gender and abdominal obesity, revealed that the highest tertiles had the highest OR for NAFLD by ultrasound and NAFLD by FLI only in men without abdominal obesity [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.83 (1.17-2.84); Ptrend = 0.03, and, respectively]. NAFLD by FLI tended to increase strongly with tertile E-DII scores in men without abdominal obesity in crude and three adjusted models [full-adjusted model: OR (95 % CI) tertile3vs.1: 3.64 (1.56-8.46); Ptrend = 0.005]. By contrast, women with abdominal obesity in the highest tertile had the highest OR for NAFLD by ultrasound in all models [full-adjusted model: OR (95 % CI) tertile3vs.1: 1.67 (1.07-2.62); Ptrend = 0.02]. CONCLUSIONS: Our results suggest that diet plays a role in regulating inflammation. Additionally, we observed an inflammatory diet predicts the risk of NAFLD in Iranian adults. However, longitudinal studies are required in order to further substantiate the utility of the DII in the development of more effective dietary interventions among populations at risk of chronic disease.

A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis.

Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population. Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years. Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis.

AIM: We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia. METHODS: Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed. RESULTS: TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized ß = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized ß = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis. CONCLUSION: Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.

Atypical Presentation of Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare rheumatic disorder with various presentations. It is diagnosed based on the Yamaguchi criteria, besides the exclusion of infectious diseases and other rheumatic disorders and malignancies. Here, we describe a case of a young man, presenting with remittent fever, abdominal pain, and persistent nausea. Further evaluations showed elevated acute phase reactants, abnormal levels of liver transaminase, multiple lymphadenopathies, and pleural effusion. He was finally diagnosed with AOSD and responded well to corticosteroids and methotrexate. We describe the present case to alert gastroenterologists to AOSD as a rare differential diagnosis in patients with persistent gastrointestinal symptoms.

Serum Alkaline Phosphate Level Associates with Metabolic Syndrome Components Regardless of Non-Alcoholic Fatty Liver; A Population-Based Study in Northern Iran.

Background: Serum alkaline phosphatase (ALP) is an indicator of hepatobiliary disorders, such as metabolic syndrome (MetS). To assess the association between serum ALP levels and MetS, with or without non-alcoholic fatty liver disease (NAFLD), in a cohort study in northern Iran. Methods: Data from approximately 5257 subjects aged more than 18 years participating in the Amol cohort were used. We extracted the required data and investigated the correlation between liver enzyme levels and MetS. Multiple logistic regression analyses based on the serum ALP quartiles were performed. Results: Of them, 2860 were male with a mean age of 42.11±16.1 years. A positive linear trend was observed between serum ALP levels and the number of MetS components in both sexes. In both sexes, systolic blood pressure, waist circumferences, and high-density lipoprotein (HDL) had a significant association with ALP. After adjusting for age, both sexes with NAFLD showed an increased risk of developing MetS. The risk of NAFLD increased in individuals with>2nd quartile of ALP. Furthermore, higher ALP levels were associated with an increased risk of MetS in males (1.1014 [0.782-1.315]) and females (1.441 [1.085-1.913]). Conclusion: There is a significant association between serum ALP levels and MetS, independent of fatty liver changes, suggesting that this marker can be considered as a feasible predictor of MetS.