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Background and aim: It is generally accepted that oral health literacy is one of the important determinants of oral health. The aim of this study was to evaluated oral health literacy in Sari City -Northern Iran. Methods: This cross-sectional study was carried out on 855 adult citizens of Sari by random sampling. The data was collected using a standard questionnaire including 17 questions regarding oral health literacy in four sections: content comprehension, number comprehension, listening and decision making; three questions about oral health behaviors and some questions about self-assessment of oral health status, age, gender and education. Citizens were divided into three groups in terms of oral health literacy: inadequate (0-9), marginal (10-11), and adequate (12-17). The data was analyzed using descriptive and analytical statistics including chi-square, t-test, ANOVA and correlation coefficient in SPSS ver. 20 software. Results: 43.3% of the Sari city citizens had adequate oral health literacy. The mean score of oral health literacy was 10.02 ± 3.4 out of 17. Oral health literacy was higher among educated and employed people, as well as those with smaller households. Those who reported better oral health behaviors had higher oral health literacy than others (P-value

Background Recurrent aphthous stomatitis (RAS) is a common lesion that affects the oral mucosa. There are several methods to treat RAS, including systemic and topical formulations. This study was conducted to evaluate the anti-inflammatory effect of topical zinc sulfate and its efficacy in the treatment of RAS. Methods A double-blind randomized clinical trial was conducted on 46 patients with RAS. They were randomly assigned into two groups to receive a zinc sulfate mucoadhesive tablet or placebo for 7 days. The pain severity was measured at baseline and daily while the diameter of the lesion was measured at baseline and on days 3, 5, and 7. The obtained data were analyzed in SPSS V.16. Results There was no significant difference in the mean diameter of lesions and pain at baseline between the two groups (P = 0.643 and P = 0.842, respectively). However, on the third, fifth, and seventh days of the study, the diameter of the lesion significantly reduced in the intervention group (P = 0.001) and the pain intensity became significantly different between groups from the fourth day of the study (P = 0.001). Conclusion Zinc sulfate mucoadhesive tablet was effective in recovery and reducing the pain and diameter of the aphthous lesion and could be considered for the treatment of RAS. Trial registration Evaluation of the effectiveness of zinc sulfate mucoadhesive tablet in the improvement of recurrent aphthous stomatitis (RAS), IRCT20151109024975N9. Registered August 1, 2018, https://en.irct.ir/trial/32423. This project was registered by the Iranian Registry of Clinical Trials (http://www.irct.ir). The IRCT ID was IRCT20151109024975N9.

Introduction Oral mucositis is a common debilitating complication of cancer treatments, particularly chemotherapy and radiation. Objectives The purpose of this study was to improve oral mucositis prevention and control among cancer patients through the implementation of best practice guidelines in a tertiary referral center in Northern Iran. Methods A clinical audit design was utilized in this implementation project. A preimplementation audit was conducted against nine best practice criteria for the prevention and treatment of oral mucositis among new cases of cancer patients in November and December 2019. Fifty cancer patients and 20 nurses participated in this phase of the clinical audit. The next step included a facilitated multidisciplinary focus group identifying targeted strategies and implementing them, completed in late December 2019. A postimplementation audit was then conducted on another 50 cancer patients and the same 20 nurses in January and early February 2020. The project utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice software. Results The preimplementation audit revealed gaps between the current practice and best practice across eight of the nine criteria. After implementing the targeted strategies, the outcomes improved across most of the criteria in the follow-up audit: 80% increase was observed in compliance of staff education, 100% increase in providing standard oral hygiene protocol in place, 64% increase in carrying out a dental examination and conducting initial oral cavity examination, and also 34% increase in conducting of ongoing oral cavity examination by a dentist, and finally 100% increase in providing preventive and therapeutic oral care regimens in place and oral pain assessment using a validated tool. Conclusion The results of this project indicate that clinical auditing is an effective approach to the assessment of evidence-based care practices for oral mucositis among new cancer patients. Evidence-based oral mucositis management among cancer patients can be achieved by educating the patients and nursing staff using the newest guidelines and dentists' comprehensive dental and oral hygiene examinations.

Compared to the prevalence and complications, there is still limited evidence in this regard.With an incidence rate of 200,000 cases annually and the induction of numerous complications, caustic ingestion imposes a significant burden on the healthcare system. Apart from being fatal in some cases, this injury affects its victims' quality of life as it is followed by many gastrointestinal problems. This injury mainly occurs accidentally among children, whereas in adults, it often occurs with suicidal intentions. Despite recent advances in internal medicine, gastroenterology, and toxicology, this type of injury remains a debilitating and, in some cases, fatal disorder for its victims.This study retrospectively evaluated the clinical, laboratory, and endoscopic findings of 150 patients admitted to a referral center of toxicology and forensic medicine and assessed factors associated with each type of injury.The findings indicated a mortality rate as high as 7.3% in this population. Age, pH, and previous medical conditions were associated with more complications. Higher degrees of injury were also significantly associated with higher mortality. No significant difference was observed between types of corrosive substances.It seems that the most effective intervention for controlling caustic ingestion injuries would be psychiatric support, primary healthcare, and household education.

Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By acting upon particular, G-protein coupled adenosine receptors, i.e., A1, A2- a & b, and A3 receptors mediate a variety of intracellular and immunomodulatory actions. Several studies have elucidated Adenosine's effect and its up-and downstream molecules and enzymes on the anti-tumor response against several types of cancers. We have also targeted a couple of molecules to manipulate this pathway and get the immune system's desired response in our previous experiences. Besides, the outgrowth of the studies on ocular Adenosine in recent years has significantly enhanced the knowledge about Adenosine and its role in ocular immunology and the inflammatory response of the eye. Glaucoma is the second leading cause of blindness globally, and the recent application of Adenosine and its derivatives has shown the critical role of the adenosine pathway in its pathophysiology. However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma.

Background and Purpose: Denture stomatitis is a chronic inflammation disease of the oral mucosa, which is specified by erythematous lesions mainly in the upper palate. Nystatin as a polyene, a class of antifungal agents, is one of the effective drugs to treat denture stomatitis. Considering the expansion of utilizing herbal drugs to cure many kinds of diseases, the present study was conducted to investigate the effects of Camellia sinensis (green tea), which has the most chemical and influence similarity with nystatin, against denture stomatitis. Materials and Methods: This study was conducted on 22 patients with a positive mycological evidence for denture stomatitis caused by Candida species. The study population was divided into two groups, namely green tea and nystatin, receiving green tea mouthwash 0.5% and nystatin suspension 100,000 U/ml, respectively. The lesion size and number of yeast colonies were measured before and after the treatment. Results: According to the results, both groups showed reduced lesion size, clinical improvement, and significant reduction of Candida colony count in both group of patients were showedafter the therapeutic. Based on the results of polymerase chain reaction, Candida albicans was the most common species isolated from denture stomatitis. There was no significant difference between the two study groups in terms of Candida species distribution (P=0.700). Conclusion: Green tea demonstrated a comparable anti-Candida activity with regard to nystatin; therefore, it could be recommended as an alternative treatment.

High levels of lipids in saliva are associated with high decay because they have adverse effects on the protective role of saliva. Our goal is to investigate the level of saliva cholesterol and triglyceride in type 2 diabetic patients and to determine the relationship between these saliva parameters and the status of dental decay. In this casecontrol study, a total 100 patients with diabetes, 50 with high triglycerides and cholesterol and 50 with normal range of these parameters (control) participated in the study. Both groups had at least 22 teeth. Non-stimulated saliva was collected from each individual for 5 minutes. All five tooth surfaces were examined for decay and DMFT of patients was recorded. According to the analysis, there was a significant relationship between serum cholesterol and saliva cholesterol, and also between serum triglyceride and saliva triglyceride. Carbohydrate, FBS, and HbA1c showed a relationship with years of having diabetes mellitus, but salivary cholesterol did not related to age of patients. Salivary triglyceride had a significant relationship only with years of having diabetes not with FBS, HbA1C and age of patients, also decay had a significant relationship with the age of the patients, and years of having diabetes, but it did not have relationship with blood glucose levels. In the study group, salivary cholesterol and DMFT showed a significant relationship, however, saliva triglyceride was not associated with DMFT in study and control group. In our study, it was found that there was a significant relationship between decay, missing, and filled teeth (DMFT) and salivary cholesterol, but this relationship was not found between salivary triglyceride and decay.

Supplemental Digital Content is available in the text., OBJECTIVES: There is increasing evidence of cardiovascular morbidity associated with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). Pro-B-type natriuretic peptide is a biomarker of myocardial stress, associated with various respiratory and cardiac outcomes. We hypothesized that pro-B-type natriuretic peptide level would be associated with mortality and clinical outcomes in hospitalized coronavirus disease 2019 patients. DESIGN: We performed a retrospective analysis using adjusted logistic and linear regression to assess the association of admission pro-B-type natriuretic peptide (analyzed by both cutoff > 125 pg/mL and log transformed pro-B-type natriuretic peptide) with clinical outcomes. We additionally treated body mass index, a confounder of both pro-B-type natriuretic peptide levels and coronavirus disease 2019 outcomes, as an ordinal variable. SETTING: We reviewed hospitalized patients with coronavirus disease 2019 who had a pro-B-type natriuretic peptide level measured within 48 hours of admission between March 1, and August 31, 2020, from a multihospital U.S. health system. PATIENTS: Adult patients (≥ 18 yr old; n = 1232) with confirmed coronavirus disease 2019 admitted to the health system. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for demographics, comorbidities, and troponin I level, higher pro-B-type natriuretic peptide level was significantly associated with death and secondary outcomes of new heart failure, length of stay, ICU duration, and need for ventilation among hospitalized coronavirus disease 2019 patients. This significance persisted after adjustment for body mass index as an ordinal variable. The adjusted hazard ratio of death for log transformed pro-B-type natriuretic peptide was 1.56 (95% CI, 1.23–1.97; p < 0.0001). CONCLUSIONS: Further investigation is warranted on the utility of pro-B-type natriuretic peptide for clinical prognostication in coronavirus disease 2019 as well as implications of abnormal pro-B-type natriuretic peptide in the underlying pathophysiology of coronavirus disease 2019–related myocardial injury.

Cancer immunotherapy aims to enhance the immune system reactivity against tumour cells. Chimeric Antigen Receptor (CAR), presented on the surface of the T cells, specifically redirects the cell and demonstrates significant promises in treating patients with different types of haematologic malignancies. Although several cases of improvement have been reported, clinical experiences, such as excessive activity, poor control, toxicity and limited life span of conventional CAR T cells have emerged as treatment challenges associated with this therapeutic strategy. Recently, multiple switchable CAR T platforms have been made to enable better control in a dose-dependent manner, which is correlated to distinct characteristics of different switch molecules. This review aimed at a brief represention of toxicities of the CAR T cells, the obstacles facing tumour treatments especially in solid tumours, and finally providing a framework for classification of the newly developed Conjugated/Split CAR-T cell technologies to overcome difficulties. Overall, Newly developed Conjugated CAR T cells using among with soluble switch molecules seems to be as responsive as the conventional CAR T cells, yet providing many new useful options to effectively overcome limitations and significantly improve patient safety.

Background and Purpose: Denture stomatitis is a chronic inflammation disease of the oral mucosa, which is specified by erythematous lesions mainly in the upper palate. Nystatin as a polyene, a class of antifungal agents, is one of the effective drugs to treat denture stomatitis. Considering the expansion of utilizing herbal drugs to cure many kinds of diseases, the present study was conducted to investigate the effects of Camellia sinensis (green tea), which has the most chemical and influence similarity with nystatin, against denture stomatitis. Materials and Methods: This study was conducted on 22 patients with a positive mycological evidence for denture stomatitis caused by Candida species. The study population was divided into two groups, namely green tea and nystatin, receiving green tea mouthwash 0.5% and nystatin suspension 100,000 U/ml, respectively. The lesion size and number of yeast colonies were measured before and after the treatment. Results: According to the results, both groups showed reduced lesion size, clinical improvement, and significant reduction of Candida colony count in both group of patients were showedafter the therapeutic. Based on the results of polymerase chain reaction, Candida albicans was the most common species isolated from denture stomatitis. There was no significant difference between the two study groups in terms of Candida species distribution (P=0.700). Conclusion: Green tea demonstrated a comparable anti-Candida activity with regard to nystatin; therefore, it could be recommended as an alternative treatment.

BACKGROUND Galectin-3 (Gal-3) has been associated with heart failure (HF) and poor cardiovascular outcomes. However, the effect of longitudinal changes in Gal-3 on clinical outcomes remains unclear.OBJECTIVES The authors sought to study clinical determinants of change in Gal-3 among community-dwelling individuals. Further, they sought to examine the role of serial Gal-3 measurements in predicting risk of future HF, cardiovascular disease (CVD), and mortality.METHODS A total of 2,477 participants in the Framingham Heart Study Offspring cohort underwent measurement of plasma Gal-3 levels at 2 examinations (1995 to 1998 and 2005 to 2008). Linear regression models were used to examine clinical correlates of change in Gal-3. Proportional hazards models were used to relate future clinical outcomes with change in Gal-3.RESULTS The following clinical correlates were associated with greater longitudinal increases in Gal-3 levels: age, female sex, hypertension, diabetes, body mass index, interim development of chronic kidney disease, and HF (p CONCLUSIONS Longitudinal changes in Gal-3 are associated with traditional cardiovascular risk factors and renal disease. In turn, change in Gal-3 predicts future HF, CVD, and mortality in the community. Future studies are needed to determine whether serial Gal-3 measures may be useful in disease prevention. (J Am Coll Cardiol 2018; 72: 3246-54) (c) 2018 by the American College of Cardiology Foundation.

Background: Oral mucositis is defined as oral mucosal inflammation in cancer patients that is caused by chemotherapy and/or radiotherapy. Propolis is a natural product produced by bees and has antimicrobial, antioxidant, and anti-inflammatory effects. Therefore, considering the anti-inflammatory properties of Propolis, the aim of this study is to evaluate the efficacy of Propolis tablet on oral mucositis caused by chemotherapy. Materials and Methods: In this randomized, double-blinded, placebo-controlled study, 50 patients were enrolled in the study, and samples were taken from patients on Folfox chemotherapy regimen with colon cancer who were admitted to the Oncology Center of Imam Khomeini Hospital in Sari. The patients were then divided into two groups of 25. The first group received 50 mg Propolis tablets as 2 tablets per day for 21 days and the second group received placebo. All patients were examined by oral medicine specialist after initial examination, weekly and for 3 weeks, and the severity of mucositis was recorded according to WHO criteria. Data analysis was performed in SPSS ver. 22 software using T test and Mann-Whitney and Kruskal-Wallis tests. Results: The age range of the participants in the study was between 26-72 years. In the intervention group 13 women (52%) and 12 men (48%) and in the control group 13 women (52%) and 12 men (48%) participated .In this study, there was a significant difference in the mean of oral mucositis severity in the Propolis group compared to placebo group. In the intervention group, oral mucositis grade was significantly lower in the 2nd and 3rd follow up sessions than in the placebo group (p

We appreciate the interest in our paper [(1)][1] by Dr. Oikonomou and colleagues, and read with interest their recently published work on galectin-3 (Gal-3) in heart failure [(2)][2]. Taken together, we agree that Gal-3 may be a promising and informative biomarker with respect to development of

Introduction Iron deficiency anemia (IDA) is a common comorbidity among patients with heart failure (HF). There is ongoing data suggesting the importance of balanced iron homeostasis amongst patients with HF. However, little is known about the clinical impact of IDA in patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Hypothesis The aim of this study was to assess the impact of IDA on HF hospitalizations by HF subtype, i.e. HFpEF and HFrEF. Methods We queried the National Inpatient Sample (NIS), Health Care and Utilization Project (HCUP) database from 2008 to 2014 for patients ≥ 18 years old with a primary discharge diagnosis of HF based on the Clinical Classifications Software code 108. Patients were further stratified to HFpEF using ICD-9 codes 428.3x and HFrEF using ICD-9 codes 428.2x, and 428.4x. IDA was identified using ICD-9 codes 280.1, 280.9, and 280.8. Primary outcome of interest was length of stay (LOS) and total hospital charges by HF subtypes. Secondary outcome was readmission score estimated using Elixhauser-based comorbidities by HF subtypes. Multivariable- adjusted regression models were used to examine the impact of IDA on outcomes. Hospital trend weights were accounted in all models. All analyses were performed using SAS 9.4. Results A total of 1,684,227 patients with primary diagnosis of HFpEF (mean age 76±13, 64% female) and 2,675,477 patients with primary diagnosis of HFrEF (mean age 71±15, 41% female) were identified and included in the study. Prevalence of IDA was significantly higher among patients with HFpEF as compared to HFrEF (6.1 vs. 4.6%, p Conclusions Prevalent IDA is associated with significantly longer hospital stay, higher total hospital charges, and increased likelihood of readmission in both HFpEF and HFrEF patient populations. Parallel clinical results in both HFpEF and HFrEF implicate a potential benefit of addressing IDA in all HF patients regardless of subtype.

To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m2) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state.

Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.

Backgrounds: Lichen planus is a chronic systemic disease and oral mucosa is commonly involved. Oral lichen planus (OLP) most commonly affects middle-aged women. The prevalence of the disease ranges between 0.5% and 2.6% in the general population and the range of malignant transformation varies between 0% and 10%. Objectives: To assess the rate of malignant transformation of OLP samples. Materials and Methods: This retrospective study was carried out on 112 medical records of patients with histological diagnosis of OLP who attended the Department of Pathology at the Educational Hospital from 2005 to 2012. H&E-stained slides were reviewed by two pathologists using strict clinical and histopathological diagnostic World Health Organization (WHO) criteria. Dysplastic changes were diagnosed and graded according to the latest WHO classification. Results: Of the 112 cases diagnosed as OLP, there were 39 males and 73 females and the patients' ages ranged from 15 to 86 years (mean age 44.5 years). The erosive form with fifty cases was the most common clinical type and the papular type with one case was the least common clinical type. Regarding the site, the buccal mucosa was the most common site with 52 cases. Totally, dysplastic changes were found in 12 samples, among them five cases showed mild dysplasia and seven cases showed moderate dysplasia. One case developed oral squamous cell carcinoma after 3 years. Conclusion: OLP is considered as a premalignant condition by the WHO and several authors. Although the malignancy rate is not so high, to reduce morbidity and mortality from cancer arising on OLP lesions, a regular follow-up examination is recommended.

BACKGROUND Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations. METHODS We measured sST2 using a highly sensitive ELISA in 3450 Framingham Heart Study participants who attended a routine examination. We used multivariable linear regression models to identify covariates associated with sST2 in the general sample. We obtained a reference sample (n = 1136) by excluding individuals with prevalent coronary disease, heart failure, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, left ventricular systolic dysfunction, and pulmonary and renal dysfunction. We used empiric and quantile regression techniques to estimate the 2.5th, 50th, 97.5th, and 99th quantiles. RESULTS In the general sample (mean age 59 years, 55% women), systolic blood pressure (P = 0.006), antihypertensive medication use (P = 0.03), and diabetes (P < 0.001) were associated with sST2 concentrations. In the reference sample (mean age 55, 59% women), male sex (P < 0.0001) and older age (P = 0.004) were predictive of higher sST2 concentrations. Quantile and empirical methods were used to define the reference intervals. Using the empirical approach, upper 99% percentile values in different age groups ranged from 46.6 to 64.4 μg/L in men and 36.7 to 53.0 μg/L in women. CONCLUSIONS In a well-characterized, community-based cohort, values for sST2 differ between men and women, increase with age, and are associated with diabetes and hypertension.

BACKGROUND Growth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. RESULTS GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h2 = 0.38; P = 2.5 × 10−11). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 × 10−32 for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS In ambulatory individuals, both cardiometabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation.

Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome (IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore, Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort.

BACKGROUND:Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling. METHODS AND RESULTS:We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P

Nature Communications 6: Article number:6791 (2015); Published 13 April 2015; Updated 21 May 2015. In Fig. 1c,d of this Article, the y axis labels were inadvertently changed from ‘Log isocitrate’ to ‘Log aconitase’ during the production process. The correct version of Fig. 1 appears below.

Background In epidemiologic studies, obesity has been associated with reduced natriuretic peptide ( NP ) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading. Methods and Results We enrolled 15 obese individuals (mean BMI 45±5.4 kg/m 2 ) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large‐volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre‐operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6‐month visit, N‐terminal pro‐atrial NP (Nt‐pro ANP ) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre‐operative visit ( P ANP induced by the saline infusion (≈50%) was similar both before and after surgery (saline, P P =0.2). Similar results were obtained for BNP and Nt‐pro BNP ; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure ( P =0.004) and heart rate ( P P =0.02). Conclusion In obese individuals, weight loss is associated with a substantial increase in the “setpoint” of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss.

BACKGROUND Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described. METHODS We measured plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995–1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT >1.5 mm), and mean common carotid artery IMT. We carried out multivariable regressions for carotid measurements vs biomarkers using linear and logistic models; P < 0.0056 was deemed statistically significant. RESULTS Maximal ICA IMT was significantly associated with plasma GDF-15 [β-estimate 0.04 per 1-U increase in log(GDF-15), SE 0.01, P < 0.0001]. Similarly, the odds of having carotid plaque increased 33% [odds ratio 1.33 per 1-U increase in log(GDF-15), 95% CI 1.20–1.48, P < 0.0001]. In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the 3 biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together. CONCLUSIONS Increased GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted.

Background Obesity is associated with cardiometabolic disease, including insulin resistance (IR) and diabetes. Cyclic guanosine monophosphate ( cGMP ) signaling affects energy balance, IR, and glucose metabolism in experimental models. We sought to examine effects of phosphodiesterase‐5 inhibition with tadalafil on IR in a pilot study of obese nondiabetic individuals. Methods and Results We conducted a randomized, double‐blinded, placebo‐controlled trial of adults age 18 to 50 years with obesity and elevated fasting insulin levels (≥10 μU/ mL ). Participants were randomized to tadalafil 20 mg daily or placebo for 3 months. Oral glucose tolerance tests were performed, and the effect of tadalafil on IR was examined. A total of 53 participants (mean age, 33 years; body mass index [BMI], 38 kg/m 2 ) were analyzed, 25 randomized to tadalafil and 28 to placebo. In the overall sample, measures of IR did not differ between tadalafil and placebo groups at 3 months. However, in individuals with severe obesity (BMI ≥36.2 kg/m 2 ), tadalafil use was associated with improved IR (homeostatic model assessment for IR), compared to placebo ( P =0.02, respectively). Furthermore, one measure of β‐cell compensation for IR (oral disposition index) improved with tadalafil in the overall sample ( P =0.009) and in the subgroup with severe obesity ( P =0.01). Conclusion Results of this pilot study did not show improvements in IR with tadalafil, compared to placebo. However, tadalafil may have favorable effects on β‐cell compensation, particularly in individuals with severe obesity. Future studies evaluating the potential metabolic benefits of cGMP modulation in obesity are warranted. Clinical Trial Registration URL: ClinicalTrials.gov. Unique Identifier: NCT01444651.

Background Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow‐up. Methods and Results Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P =0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P P P =0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P =0.001). Conclusions Individuals with a higher heart rate are at elevated long‐term risk for cardiovascular events, in particular, heart failure, and all‐cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation.

Objective To examine the relation of endothelial microparticles (EMPs) with cardiometabolic risk in the community. Background Circulating EMPs are small membrane vesicles released after endothelial cell injury. Endothelial microparticles are reportedly increased among individuals with a high burden of cardiovascular risk factors. However, prior investigations have been limited to small, highly selected samples. Methods We studied 844 individuals without a history of cardiovascular disease in the Framingham Offspring cohort (mean age 66 ± 9 years, 57% women). We used standardized flow cytometry methods to identify and quantify circulating CD144+ and CD31+/CD41− EMPs. We then used multivariable regression analyses to investigate the relations of EMP phenotypes with cardiovascular and metabolic risk factors. Results In multivariable analyses, the following cardiovascular risk factors were associated with one or more of the circulating EMP populations: hypertension ( P = 0.025 for CD144+,), elevated triglycerides ( P = 0.002 for CD144+, P < 0.0001 for CD31+/CD41−), and metabolic syndrome ( P < 0.0001 for CD144+,). Overall, each tertile increase in the Framingham risk score corresponded to a 9% increase in log-CD31+/CD41− EMPs ( P = 0.022). Furthermore, the presence of hypertriglyceridaemic waist status was associated with 38% higher levels of CD144+ EMPs ( P < 0.0001) and 46% higher levels of CD31+/CD41− EMPs ( P < 0.0001). Conclusion In a large community-based sample, circulating EMP levels were associated with the presence of cardiometabolic risk factors, particularly dyslipidaemia. These data underscore the potential influence of high-risk metabolic profiles on endothelial integrity.

Introduction: Whereas physical activity (PA) reduces IHD and stroke, effects on atrial fibrillation (AF) are controversial, with concern that vigorous PA (VPA) or even moderate PA (MPA) could increase AF. In addition, little is known about the association between sedentary activity (SA) and AF. Methods: We prospectively investigated habitual PA and new-onset AF in 28,169 US men age 68±9 years and free of AF in 2002. PA was assessed biennially via validated questionnaires including 11 recreational PAs and 6 SAs. MET-hours/week of MPA (MET6), TPA (total PA), and hours/week of SA were quantified every 4 years from 1986 to 2010, and cumulatively averaged to assess long-term effects. Incident AF was evaluated from 2002 (first year of assessment) to 2010, based on self-reported physician diagnosis that was further confirmed by a supplementary questionnaire (positive predictive value 95% vs. medical records). We separately evaluated symptomatic vs. asymptomatic AF, based on prior evidence for ascertainment bias of the latter in this cohort (healthier people being more likely to be seen and diagnosed by their physician). Cox models estimated risk across quintiles of MPA, VPA, TPA, and SA. Results: During 231,108 person years of follow-up, 782 incident AF cases were confirmed (493 symptomatic, 283 asymptomatic, 6 symptoms unknown). In multivariable analyses, there was no significant association between MET-hours/week of MPA, VPA, or TPA and risk of symptomatic AF (p-value < 0.05) (Table). Also, hours/week of SA and TV watching were not associated with AF risk. These results remained the same after mutual adjusting for other activities, after further adjusting for potential confounders or mediators, or after excluding baseline CVD. Similar results were seen for asymptomatic and total AF. Conclusion: In this cohort of middle-aged men, neither PA nor SA was significantly associated with risk of AF.