Development and Validation of a Protein Risk Score for Mortality in Heart Failure : A Community Cohort Study.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome with high mortality. Current risk stratification approaches lack precision. High-throughput proteomics could improve risk prediction. Its use in clinical practice to guide the management of patients with HF depends on validation and evidence of clinical benefit. OBJECTIVE: To develop and validate a protein risk score for mortality in patients with HF. DESIGN: Community-based cohort. SETTING: Southeast Minnesota. PARTICIPANTS: Patients with HF enrolled between 2003 and 2012 and followed through 2021. MEASUREMENTS: A total of 7289 plasma proteins in 1351 patients with HF were measured using the SomaScan Assay (SomaLogic). A protein risk score was derived using least absolute shrinkage and selection operator regression and temporal validation in patients enrolled between 2003 and 2007 (development cohort) and 2008 and 2012 (validation cohort). Multivariable Cox regression was used to examine the association between the protein risk score and mortality. The performance of the protein risk score to predict 5-year mortality risk was assessed using calibration plots, decision curves, and relative utility analyses and compared with a clinical model, including the Meta-Analysis Global Group in Chronic Heart Failure mortality risk score and N-terminal pro-B-type natriuretic peptide. RESULTS: The development (n = 855; median age, 78 years; 50% women; 29% with ejection fraction <40%) and validation cohorts (n = 496; median age, 76 years; 45% women; 33% with ejection fraction <40%) were mostly similar. In the development cohort, 38 unique proteins were selected for the protein risk score. Independent of ejection fraction, the protein risk score demonstrated good calibration, reclassified mortality risk particularly at the extremes of the risk distribution, and showed greater clinical utility compared with the clinical model. LIMITATION: Participants were predominantly of European ancestry, potentially limiting the generalizability of the findings to different patient populations. CONCLUSION: Validation of the protein risk score demonstrated good calibration and evidence of predicted benefits to stratify the risk for death in HF superior to that of clinical methods. Further studies are needed to prospectively evaluate the score's performance in diverse populations and determine risk thresholds for interventions. PRIMARY FUNDING SOURCE: Division of Intramural Research at the National Heart, Lung, and Blood Institute of the National Institutes of Health.

Proteomics for heart failure risk stratification: a systematic review.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality. METHODS: We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool. RESULTS: Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies. CONCLUSIONS: In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.

Saccharomyces boulardii improves clinical and paraclinical indices in overweight/obese knee osteoarthritis patients: a randomized triple-blind placebo-controlled trial.

PURPOSE: This study aimed to determine the effect of the probiotic Saccharomyces boulardii (S. boulardii) in patients with knee osteoarthritis (KOA). METHODS: In this study, 70 patients with KOA were recruited via outpatient clinics between 2020 and 2021 and randomly assigned to receive probiotics or placebo supplements for 12 weeks. The primary outcome was a change in pain intensity according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. RESULTS: Sixty-three patients completed the trial. A linear mixed analysis of covariance (ANCOVA) model analysis showed that probiotic was better than placebo in decreasing the pain intensity measured by visual analogue scale (VAS) [-2.11 (-2.59, -1.62) in probiotic group and -0.90 (-1.32, -0.48) in placebo group, p = 0.002] and WOMAC pain score [-3.57 (-4.66, -2.49) in probiotic group and -1.43 (-2.33, -0.53) in placebo group, p < 0.001]. The daily intake of acetaminophen for pain management significantly decreased in the probiotic group [-267.18 (-400.47, -133.89) mg, p < 0.001] that was significantly better than placebo (p = 0.006). Probiotic significantly decreased the serum levels of high-sensitivity C-reactive protein (hs-CRP) inflammatory index [-2.72 (-3.24, -2.20) µg/ml] and malondialdehyde (MDA) oxidative stress index [-1.61 (-2.11, -1.11) nmol/ml] compared to the placebo (p = 0.002 and p < 0.001, respectively). Probiotic was better than placebo in increasing the scores of role disorder due to physical health (p = 0.023), pain (p = 0.048) and physical health (p = 0.031). CONCLUSION: Probiotic S. boulardii supplementation in patients with KOA significantly improved pain intensity, some dimensions of QoL, and inflammatory and oxidative stress biomarkers with no severe side effects. TRIAL REGISTRY: Registered on the Iranian clinical trial website ( http://www.irct.ir : IRCT20161022030424N4) on 2019-09-02.

The effects of Garcinia cambogia (hydroxycitric acid) on lipid profile: A systematic review and meta-analysis of randomized controlled trials.

Garcinia cambogia (GC) has antioxidant, anticancer, antihistamine, and antimicrobial properties. To determine the effect of GC on lipid profiles, a systematic review and meta-analysis was carried out. Up to February 9, 2023, six electronic databases (Web of Science, Cochrane Library, Embase, PubMed, Scopus, and Google Scholar) were searched at any time without limitations. Trials examining the impact of GC on serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in adults were included. The total effect was shown as a weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis approach. This systematic review and meta-analysis included 14 trials involving 623 subjects. Plasma levels of TC (WMD: -6.76 mg/dL; CI: -12.39 to -0.59, p-value = 0.032), and TG (WMD: -24.21 mg/dL; CI: -37.84 to -10.58, p < 0.001) were significantly reduced after GC use, and plasma HDL-C (WMD: 2.95 mg/dL; CI: 2.01 to 3.89, p < 0.001) levels increased. low-density lipoprotein cholesterol levels (WMD: -1.15 mg/dL; CI: -16.08 to 13.78, p-value = 0.880) were not significantly affected. The effects of lowering TC and TG were more pronounced for periods longer than 8 weeks. Consuming GC has a positive impact on TC, TG, and HDL-C concentrations. The limitations of this study include the short duration of analyzed interventions and significant heterogeneity. Nevertheless, it is imperative to conduct well-structured, and high-quality long-term trials to comprehensively evaluate the clinical effectiveness of GC on lipid profile, and validate these findings.

Higher intakes of fiber, total vegetables, and fruits may attenuate the risk of all-cause and cause-specific mortality: findings from a large prospective cohort study.

BACKGROUND: Although studies have reported an inverse association between fruits, vegetables, and fiber consumption and all-cause and cause-specific mortality, the issue remains incompletely defined in the Middle Eastern population. AIMS: The current study aimed to investigate the association between dietary fiber, fruit, and vegetable intake and all-cause and cause-specific mortality. METHODS: A total of 48632 participants (mean age = 52years), 57.5% (n = 27974) women and 42.5% (n = 20658) men, were recruited from an ongoing large-scale prospective cohort study (the Golestan Cohort Study (GCS)), in the north of Iran. Using a validated semi-quantitative 116-item food questionnaire, dietary intakes were collected. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of all-cause and cause-specific mortality were reported. RESULTS: After approximately 14 years of follow-up, 10,774 deaths were recorded. In the fully adjusted model, compared to those in the lowest quintile of intake, those in the second and third quintiles of dietary fiber intake had a 7%-10% reduction in risk of all-cause mortality, and a 15%-17% reduction in the risk of mortality from other causes. Increasing consumption of fruits was also associated with a decreased risk of mortality for all-cause mortality by 9%-11%, and all cancer by 15-20%. Further, those in the third and fourth quintiles of vegetables intake had 11%-12% lower risk for CVD mortality. DISCUSSION: The results from the GCS further support the current recommendations on following a healthy diet containing proper amounts of fiber, vegetables, and fruits, as health-protective dietary items. CONCLUSIONS: Higher intake of dietary fiber, fruits, and vegetables has the potential to reduce both overall and cause-specific mortality rates. However, additional cohort studies with larger sample size and long-term follow-up durations are required to establish these findings.

Meat consumption and risk of esophageal and gastric cancer in the Golestan Cohort Study, Iran.

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high-risk population. The Golestan Cohort Study (GCS) is a population-based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow-up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non-cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00-1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00-1.17) and red meat separately (HR 1.09, 95% CI = 1.00-1.18). The HR for red meat and non-cardia GC was 1.23 (95% CI = 1.02-1.48). No associations were observed for other types of meat. In conclusion, in this high-risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC.

Comparing the risk of cardiovascular diseases and all-cause mortality in four lifestyles with a combination of high/low physical activity and healthy/unhealthy diet: a prospective cohort study.

BACKGROUND: In this study, we assessed the risk of cardiovascular diseases (CVDs) and all-cause mortality in subjects having an only physical activity or a healthy diet or both compared to those having none of these healthy behaviors in the Golestan Cohort Study (GCS). METHODS: A total of 50,045 participants aged ≥ 40 years were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a median of 13.9 years. Four lifestyles were compared: healthy diet and active (HDA), healthy diet but inactive (HDI), unhealthy diet but active (UDA), and unhealthy diet and inactive (UDI), with UDI being considered as the reference group. Diet quality was assessed by the Dietary Approaches to Stop Hypertension diet score, which was calculated based on a validated food frequency questionnaire. The primary outcomes were death from any cause and CVDs. Adjusted Cox models were used to estimate the hazards ratio (HR) and 95% confidence intervals (CI) for overall and CVDs mortality. RESULTS: During 467,401 person-years of follow-up, 6,256 overall deaths and 2,043 confirmed CVDs deaths were reported. After adjustment for potential confounders, there was a significant lower risk for all-cause mortality in participants with both healthy behaviors (HR = 0.79, 95% CI = 0.73 to 0.86) or only one healthy behavior [HDI: HR = 0.84, 95% CI = 0.78 to 0.90)] and [UDI: HR = 0.91, 95% CI = 0.85 to 0.97] compared to those with both unhealthy behaviors. For CVDs mortality, the HDA lifestyle (HR = 0.74, 95%CI = 0.65 to 0.86), as well as the UDA lifestyle (HR = 0.83, 95%CI = 0.74 to 0.94) indicated a significant lower risk compared to the UDI lifestyle. The HDI lifestyle was not more effective than UDI. CONCLUSION: The greatest reduction in all-cause and CVDs mortality was related to the HDA. For all-cause mortality, both HDI and UDA lifestyles were associated with a decreased risk in comparison to UDI, but for CVDs mortality, only UDA but not HDI decreased the risk.

Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies.

PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Urinary nitrate and sodium in a high-risk area for upper gastrointestinal cancers: Golestan Cohort Study☆.

BACKGROUND: The epidemiological evidence regarding the carcinogenicity of nitrate and sodium in drinking water is limited, partly because measuring the exposure at the individual level is complex. Most studies have used nitrate in water supplies as a proxy for individual exposure, but dietary intakes and other factors may contribute to the exposure. The present study investigates the factors associated with urinary nitrate and sodium in a high-risk area for esophageal and gastric cancers. METHODS: For this cross-sectional study, we used data and samples collected in 2004-2008 during the enrollment phase of the Golestan Cohort Study from a random sample of 349 participants (300 individuals from 24 rural villages and 49 from the city of Gonbad), stratified by average water nitrate in their district, the source of drinking water, and the usual dietary intake of nitrate and sodium. Nitrate, sodium, and creatinine were measured in a spot urine sample collected at the time of interview. We used the provincial cancer registry data to calculate the cumulative incidence rates of esophageal and gastric cancers for each location through June 1, 2020, and used weighted partial Pearson correlation to compare the incidence rates with median urinary nitrate and sodium in each village or the city. RESULTS: Among 349 participants (mean age±SD: 50.7 ± 8.6 years), about half (n = 170) used groundwater for drinking, and the use of groundwater was significantly more common in high-elevation locations (75.8%). The geometric mean of the creatinine-corrected urinary nitrate concentration was 68.3 mg/g cr (95%CI: 64.6,72.3), and the corresponding geometric mean for urinary sodium was 150.0 mmoL/g cr (95%CI: 139.6,161.1). After adjusting for confounders, urinary nitrate was associated with being a woman, drinking groundwater, and living in high-elevation locations, but not with estimated dietary intake. Urinary sodium concentration was significantly associated with monthly precipitation at the time of sampling but not with elevation or drinking water source. There were significant positive correlations between both median urinary nitrate and sodium in each location and esophageal cancer incidence rates adjusted for sex and age (r = 0.65 and r = 0.58, respectively, p < 0.01), but not with gastric cancer incidence. CONCLUSION: In a rural population at high risk for esophageal and gastric cancers, nitrate excretion was associated with living at a higher elevation and using groundwater for drinking. The associations between nitrate and sodium excretion with esophageal cancer incidence warrant future investigation.

Red Meat Consumption and Risk of Nonalcoholic Fatty Liver Disease in a Population With Low Meat Consumption: The Golestan Cohort Study.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS). METHODS: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD. DISCUSSION: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944).

Dietary quality using four dietary indices and lung cancer risk: the Golestan Cohort Study (GCS).

PURPOSE: The lung cancer incidence in Iran has increased almost ten times over the past three decades. In addition to the known causes such as smoking and certain occupational exposure, dietary quality has been suggested to play a role in lung cancer. We aim to explore the association between dietary pattern and lung cancer risk among a Middle East population. METHODS: Data came from Golestan Cohort Study which included 48,421 participants with 136 lung cancer cases diagnosed during a median follow-up of 12 years. Multivariable Cox proportional hazards regression models were used to calculate the HRs and 95% CI of lung cancer risk by tertile of the four dietary index scores-the Health Eating Index (HEI)-2015, the Alternative Health Eating Index (AHEI)-2010, the Alternative Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)-Fung. RESULTS: A higher DASH-Fung score was inversely associated with risk of lung cancer after adjusting for potential confounders (tertile three vs. tertile one: HR = 0.59 (0.38-0.93); p for trend = 0.07), and pinteraction with smoking was 0.46. Similar findings were observed among current smokers with the HEI-2015 score (tertile three vs. tertile one: HR = 0.22 (0.08-0.60): p for trend < 0.01), and pinteraction between smoking and the HEI-2015 score was 0.03. CONCLUSION: In the GCS, consuming a diet more closely aligned with the DASH diet was associated with a reduced risk of lung cancer, which appeared to be independent of smoking status. There was also an inverse link between the HEI-2015 score and lung cancer risk among current smokers. Our finding is particularly important for the Middle East population, as diet may play an important role in cancer prevention and overall health.

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

BACKGROUND: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies. OBJECTIVE: To examine the prospective associations of total and types of legume intake with the risk of incident T2D. METHODS: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity. RESULTS: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy. CONCLUSIONS: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.

Association of depression, anxiety and menopausal-related symptoms with demographic, anthropometric and body composition indices in healthy postmenopausal women.

BACKGROUND: The termination of the menstrual cycle is correlated with a number of physiological alterations and symptoms that can negatively impact emotion and mood. We aimed to investigate the association of anxiety, depression, and menopausal related symptoms with demographic, anthropometric, and body composition indices in healthy postmenopausal women. METHODS: A total of 320 menopausal women were selected randomly from referrals of health centers between January and June 2018 in Tabriz/Iran. All participants completed a demographic questionnaire. Bioelectrical impedance analysis was applied to evaluate body fat mass (BFM), soft lean mass (SLM), and lean body mass (LBM) of participants. The modified Kupperman index, Beck's depression inventory-II, and Spielberger's state-trait anxiety inventory were applied to measure the severity of menopausal-related symptoms, the frequency, and severity of the symptoms of depression and state (SA) and trait anxiety (TA), respectively. RESULTS: Finally, 245 postmenopausal women with age of 55.33 ± 4.48 years and body mass index (BMI) of 27.96 ± 3.22 kg/m2 were studied. Women with the age of 55 years and older (OR 3.928, 95% CI 1.504-10.256) and also women with mild physical activity (OR 10.104, 95% CI 3.785-26.976) had a greater possibility of having mild and moderate depression in comparison with women less than 50 years old and women with moderate and severe physical activity. Moderate and severe physical activity was correlated with a lower possibility of having medium upward, relatively severe and severe TA in comparison with participants with mild physical activity in these women (OR 0.372, 95% CI 0.151-0.917). Women with higher BMI and BFM had and more severe menopause-related symptoms (r = 0.143, p = 0.025 and r = 0.139, p = 0.030, respectively) and more severe TA symptoms (r = 0.198, p = 0.018 and r = 0.151, p = 0.021, respectively). Women with lower LBM (r = - 0.139, p = 0.031) and lower SLM (r = - 0.128, p = 0.047) had more severe depressive symptoms. CONCLUSION: Postmenopausal women with higher age and lower physical activity had a greater possibility of having mild and moderate depression. Lower physical activity was also correlated with a greater possibility of having medium upward to severe TA symptoms. Postmenopausal women with higher BMI and BFM had more severe menopause-related and TA symptoms. Women with lower LBM and SLM had more severe depressive symptoms.

Lower serum levels of alpha tocopherol and lycopene are associated with higher pain and physical disability in subjects with primary knee osteoarthritis: A case-control study.

Background: We aimed to determine dietary intake and serum concentration of α-tocopherol and lycopene in subjects with knee osteoarthritis (KOA) in relation to pain intensity and functional status and comparing them with healthy controls. Methods: This case-control study was conducted among 35 patients with primary KOA and 35 matched healthy subjects selected using convenience sampling method. Dietary intakes of alpha-tocopherol and lycopene were estimated from 24-hour dietary records. Visual Analogue Scale (VAS) and Western Ontario and McMaster (WOMAC) index were used to assess the pain and functional status, respectively. Results: Serum concentrations of alpha-tocopherol (0.024 ± 0.005 vs. 0.028 ± 0.007 µmol/ml, p-value =  0.021) and lycopene (0.616 ± 0.191 vs. 0.727 ± 0.159 µmol/l, p-value = 0.011) were significantly lower in OA patients in comparison with healthy controls. Dietary intake of alpha-tocopherol was negatively associated with total WOMAC score (r = -0.401, p-value = 0.021) and pain (r = -0.356, p-value = 0.042) and physical function (r = -0.355, p-value = 0.043) subscales. Dietary intake of lycopene was negatively associated with total WOMAC score (r = -0.616, p-value < 0.001) and pain (r = -0.348, p-value = 0.047) and physical function (r = -0.606, p-value < 0.001) subscales. Additionally, serum concentration of alpha-tocopherol was negatively associated with total WOMAC score (r = -0.574, p-value < 0.001) and physical function subscale (r = -0.571, p-value < 0.001). Serum concentration of lycopene was negatively associated with total WOMAC score (r = -0.360, p-value = 0.040) and physical function subscale (r = -0.350, p-value = 0.046) Conclusion: Serum concentrations of α-tocopherol and lycopene were significantly lower in patients with KOA than in healthy controls. Significant negative association was detected between serum concentration and dietary intake of α-tocopherol and lycopene with functional disability in patients with KOA.

The relationship between dietary patterns, dietary quality index, and dietary inflammatory index with the risk of all types of cancer: Golestan cohort study.

Background: Dietary patterns and diet quality index (DQI) are widely discussed in relation with different health conditions and have recently been taken into consideration for all cancer types. Since chronic inflammation has been recognized as an important biologic risk factor for cancer occurrence, especially in epithelial tissues, proinflammatory or anti-inflammatory characteristics of diet has become the center of attention. In the present study, we aimed to identify whether a specific dietary pattern, Mediterranean dietary score (MDs), and dietary inflammatory index (DII) were associated with overall cancer risk in Iranian population. Methods: This study was performed in the context of the Golestan cohort study. Participants with extreme daily energy intake or those who did not answer more than 30 question of the Food Frequency questionnaire (FFQ) were excluded. Dietary patterns, MDs, and DII were measured from FFQ. Age, sex, total energy, place of residence, smoking, wealth score, ethnicity, opiate use, BMI, education, marital status, and physical activity score were considered as confounding variables. Using Cox proportional hazards regression models, hazard ratios (HRs) and 95% confidence interval of cancer were estimated. Results: HRs (95% CIs) of all cancers by quartiles of Western dietary pattern, DII, and MDs showed that the forth quartile of the Western dietary pattern is attributed to 23% higher cancer risk (HRs: 1.23, CI: 1.09-1.40, P< 0.001, adjusted for age and sex) compared to the first quartile. It also remained significant after further adjustments (HRs = 1.20, CI: 1.06-1.36, P< 0.001). There was a higher cancer risk in the fourth quartile of DII in comparison with the first quartile (HRs = 1.16, CI: 1.01-1.32, P trend < 0.001, adjusted for age and sex). The lower adherence to the Mediterranean dietary pattern also largely contributes to 27% higher cancer risk (HRs: 1.27, CI: 1.12-1.44), P trend < 0.001, adjusted for age and sex), which also remained remarkable after further adjustments ((HRs =1.19, CI: 1.05-1.35, P trend < 0.001). Conclusion: Cancer is highly correlated to dietary intake and dietary patterns, such as the Western dietary pattern, while the Mediterranean diet score was inversely associated with cancer risk. Further investigations are required to get a broader insight into cancer determinants in population.

Individual and Combined Effects of Environmental Risk Factors for Esophageal Cancer Based on Results From the Golestan Cohort Study.

BACKGROUND & AIMS: Northeast Iran has one of the highest reported rates of esophageal squamous cell carcinoma (ESCC) worldwide. Decades of investigations in this region have identified some local habits and environmental exposures that increase risk. We analyzed data from the Golestan Cohort Study to determine the individual and combined effects of the major environmental risk factors of ESCC. METHODS: We performed a population-based cohort of 50,045 individuals, 40 to 75 years old, from urban and rural areas across Northeast Iran. Detailed data on demographics, diet, lifestyle, socioeconomic status, temperature of drinking beverages, and different exposures were collected using validated methods, questionnaires, and physical examinations, from 2004 through 2008. Participants were followed from the date of enrollment to the date of first diagnosis of esophageal cancer, date of death from other causes, or date of last follow-up, through December 31, 2017. Proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between different exposures and ESCC. RESULTS: During an average 10 years of follow-up, 317 participants developed ESCC. Opium smoking (HR 1.85; 95% CI 1.18-2.90), drinking hot tea (≥60°C) (HR 1.60; 95% CI 1.15-2.22), low intake of fruits (HR 1.48; 95% CI 1.07-2.05) and vegetables (HR 1.62; 95% CI 1.03-2.56), excessive tooth loss (HR 1.66; 95% CI 1.04-2.64), drinking unpiped water (HR 2.04; 95% CI 1.09-3.81), and exposure to indoor air pollution (HR 1.57; 95% CI 1.08-2.29) were significantly associated with increased risk of ESCC, in a dose-dependent manner. Combined exposure to these risk factors was associated with a stepwise increase in the risk of developing ESCC, reaching a more than 7-fold increase in risk in the highest category. Approximately 75% of the ESCC cases in this region can be attributed to a combination of the identified exposures. CONCLUSIONS: Analysis of data from the Golestan Cohort Study in Iran identified multiple risk factors for ESCC in this population. Our findings support the hypothesis that the high rates of ESCC are due to a combination of factors, including thermal injury (from hot tea), exposure to polycyclic aromatic hydrocarbons (from opium and indoor air pollution), and nutrient-deficient diets. We also associated ESCC risk with exposure to unpiped water and tooth loss.

The application of six dietary scores to a Middle Eastern population: a comparative analysis of mortality in a prospective study.

Background The associations between dietary indices and mortality have not been evaluated in populations from the Middle East, which have different dietary patterns compared to the US and Europe. In this study, we evaluated the association between six dietary indices and mortality in the Golestan Cohort Study (GCS) in Iran, which is the largest prospective study in the Middle East with 50,045 participants. Methods The six dietary indices, namely the Healthy Eating Index (HEI-2015), Alternative Healthy Eating Index (AHEI-2010), Alternative Mediterranean Diet (AMED), Dietary Approach to Stop Hypertension created by Fung (DASH-Fung) and Mellen (DASH-Mellen), and the World Cancer Research Fund (WCRF/AICR) index, were applied to data from a food frequency questionnaire, computed and divided into quintiles. Adjusted Cox models were used to estimate hazards ratio (HR) and 95% confidence intervals (CI) for overall and cause-specific mortality, using the lowest quintile as a reference group. Results Among 42,373 participants included in the current analyses, 4424 subjects died during 10.6 years of follow-up. Participants with the highest quintile dietary scores, compared with the lowest quintile dietary scores, had significantly decreased overall mortality in the AHEI-2010, AMED, DASH-Fung, and WCRF/AICR indices (HR 0.88, 95% CI = 0.80-0.97; 0.80, 0.70-0.91; 0.77, 0.70-0.86; and 0.79, 0.70-0.90, respectively). A reduced cardiovascular mortality was found for high AHEI-2010 and DASH-Fung scores (17% and 23%, respectively), and a reduced cancer mortality for high HEI-2015, AMED, and DASH-Fung scores (21, 37 and 25%, respectively). Conclusion Various indices of dietary quality are inversely associated with overall mortality, and selectively with cancer and cardiovascular mortality in the GCS, which contribute to the generalizability and validity of dietary guidelines.

Nut consumption and the risk of oesophageal squamous cell carcinoma in the Golestan Cohort Study.

BACKGROUND: Nut consumption has been inversely associated with gastric cancer incidence in US-based studies, but not with oesophageal cancer. However, there is aetiologic heterogeneity, among oesophageal squamous cell carcinoma (ESCC) cases in low-risk vs. high-risk populations. The objective of this study was to evaluate the association between nut consumption and risk of ESCC in a high-risk population. METHODS: The Golestan Cohort Study enroled 50,045 participants in Northeastern Iran, between 2004 and 2008. Intake of peanuts, walnuts and mixed nuts (including seeds) were assessed using a validated food frequency questionnaire at baseline. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals for subsequent ESCC adjusted for potential confounders. Non-consumers of nuts were used as the reference category and the consumers were categorised into tertiles. RESULTS: We accrued 280 incident ESCC cases during 337,983 person-years of follow up. Individuals in the highest tertiles of total nut consumption, and mixed nut consumption were significantly associated with lower risk of developing ESCC compared to non-consumers (HR = 0.60, 95% CI = 0.39-0.93, p-trend = 0.02, and HR = 0.52, 95% CI = 0.32-0.84, p trend = 0.002, respectively). CONCLUSIONS: We found a statistically significant inverse association between total nut consumption and the risk of ESCC in this high-risk population.

Daily Consumption of Synbiotic Yogurt Decreases Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed and developing countries. The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD. Objective: We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers, adipokine concentration, and gut peptide concentration as secondary outcomes in patients with NAFLD. Methods: In this 24-wk, open-label, randomized controlled clinical trial, 102 patients [50 men and 52 women; mean age: 40 y; body mass index (in kg/m2) (mean ± SD): 31.2 ± 4.9] were randomly assigned to 3 groups, including 2 intervention groups and 1 control group. The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle (i.e., diet and exercise). The control group was advised to follow a healthy lifestyle alone. We evaluated differences between groups in liver function measures by using repeated-measures ANOVA, ANCOVA, and logistic regression. Results: At the end of the study, the grades of NAFLD, as determined by ultrasonography, showed a significant decrease in the synbiotic group compared with the conventional and control groups (P < 0.001). The following significant mean ± SD decreases were seen in the synbiotic, conventional, and control groups, respectively: serum concentration of alanine aminotransferase (-14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L; P = 0.008), aspartate aminotransferase (-7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L; P < 0.001), alkaline phosphatase (-26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L; P = 0.024), and γ-glutamyltransferase (-6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L; P < 0.001). Conclusion: Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD. This trial was registered at the Iranian Registry of Clinical Trials website (www.irct.ir) as IRCT2017020932417N2.

Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives.

A simple synthetic route affording 27%-85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The ¹H- and (13)C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra.