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International audience; Background: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. Methods: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-totreat principle. Results: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); p= 0.60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06 to 2.62]; p=0.027); RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline: +16.7% vs.-27.5%; p= 0.024) and the incidence of acute heart failure (33% vs. 4.2%, p=0.016). Conclusion: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased BNP levels and may increase risk of acute heart failure; where possible, RAASi should be continued.

The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure (HF) in Diabetes (TRS-HFThe TRS-HFIn total, HF hospitalization occurred in 193 (3.6%) patients. Based on the TRS-HFThe TRS-HF

No abstract available.

Background: Type-2 diabetes (T2D) has been associated with increased endogenous formation of advanced glycation end products (AGEs). Their accumulation in different tissues including articular collagen, skeletal and smooth vascular muscles, or glomerular basement membranes in T2D patients have been implicated. Objective: To assess the potential association of T2D in skin ageing associated with AGEs in Chinese population.Methods: A multicentre study was conducted in Chinese population of 560 subjects aged between 50 and 70 years who were evenly assigned in two groups of 280 each, paired by health status (healthy/diabetic), gender, and age group well balanced for hormonal replacement therapy/menopausal status, body mass index (BMI), smoking status and skin characteristics. Skin conditions were examined by a dermatologist and skin autofluorescence (SAF) a marker of AGEs measured by a validated non-invasive in vivo measurement technique.Results: The results from this study confirmed the association of diabetes and skin ageing as increased AGEs accumulation were measured using SAF and contributed evidence on gender and ethnic origin on AGEs variations. This study opens the path of further investigation into the identification of significant effects of diabetes on major facial skin complexion parameters.

Aims Artificial intelligence (A.I) driven voice-based assistants may facilitate data capture in clinical care and trials; however, the feasibility and accuracy of using such devices in a healthcare environment are unknown. We explored the feasibility of using the Amazon Alexa (‘Alexa’) A.I. voice-assistant to screen for risk-factors or symptoms relating to SARS-CoV-2 exposure in quaternary care cardiovascular clinics. Methods We enrolled participants to be screened for signs and symptoms of SARS-CoV-2 exposure by a healthcare provider and then subsequently by the Alexa. Our primary outcome was interrater reliability of Alexa to healthcare provider screening using Cohen’s Kappa statistic. Participants rated the Alexa in a post-study survey (scale of 1 to 5 with 5 reflecting strongly agree). This study was approved by the McGill University Health Centre ethics board. Results We prospectively enrolled 215 participants. The mean age was 46 years (17.7 years standard deviation [SD]), 55% were female, and 31% were French speakers (others were English). In total, 645 screening questions were delivered by Alexa. The Alexa mis-identified one response. The simple and weighted Cohen’s kappa statistic between Alexa and healthcare provider screening was 0.989 (95% CI: 0.982, 0.997) and 0.992 (955 CI 0.985, 0.999) respectively. The participants gave an overall mean rating of 4.4 (out of 5, 0.9 SD). Conclusion Our study demonstrates the feasibility of an A.I. driven multilingual voice-based assistant to collect data in the context of SARS-CoV-2 exposure screening. Future studies integrating such devices in cardiovascular healthcare delivery and clinical trials are warranted. Registration https://clinicaltrials.gov/ct2/show/NCT04508972, Graphical Abstract Graphical Abstract

Background The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM ) risk stratifies patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk for heart failure (HF) hospitalization. The utility of TRS-HFDM in risk stratification for HF outcomes requires further validation. Materials and methods We used data from the control group of The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD) trial (n=5123; mean follow up 4.8 years). The TRS-HFDM includes: prior HF (2 points), atrial fibrillation (1 point), coronary artery disease (1 point), estimated glomerular filtration rate 300 mg/g; 2 point and 30-300 mg/g; 1 point). We evaluated discrimination (Harrell C index) and calibration (Nam-D Agostino calibration statistic) of TRS-HFDM for time to HF hospitalization or death due to HF. Results The mean age of participants was 62.8±6.6 years, and 38% were female. The prevalence of TRS-HFDM for 0, 1, 2, 3 and 4+ were 42.1%, 34.9%, 14.6%, 6.0%, and 2.5% respectively. Increasing TRS-HFDM corresponded to an increasing HF risk: 1.3/1000 person years (PY) (TRS-HFDM : 0) to 64.7/1000 PY (TRS-HFDM : 4+). TRS-HFDM demonstrated robust discrimination for HF outcomes (C-index 0.78). Furthermore, the score was well calibrated for HF outcomes (calibration statistic p=0.13). Similar results were seen in participants without baseline HF (C-index 0.75). Conclusion The TRS-HFDM discriminates for HF specific risk among people with T2DM. Using the TRS-HFDM to identify those who maximally benefit from therapies that reduce HF risk warrants evaluation. This article is protected by copyright. All rights reserved.

A sufficiently advanced extraterrestrial civilization can send out a swarm of self-replicating probes for space exploration. Given the fast-growing number of such a probe, even if there is only one extraterrestrial civilization sending out such probes in the Milky Way galaxy, we should still expect to see them. The fact that we do not consists part of the Fermi paradox. The suggestion that self-replicating probes will eventually mutate to consume their progenitors and therefore significantly reduce the number of total probes has been investigated and dismissed in the literature. In this work, we re-visit this question with a more realistic Lotka-Volterra model, and show that mutated probes would drive the progenitor probes into "extinction", thereby replacing them to spread throughout the galaxy. Thus, the efficiency of mutated probes in reducing the total number of self-replicating probes is even less than previously thought. As part of the analysis, we also suggest that, somewhat counter-intuitively, in designing self-replicating probes, one should not program them to stop replicating when sufficient mutation causes the probes to fail to recognize the progenitor probes as "self"., Comment: Revised version to appear in EPJ Plus

Objective: We conducted this study to explore the effect of oral probiotic supplementation on hair density as a primary outcome in subjects with hair loss and at high risk of metabolic syndrome. The secondary objectives were to assess probiotic effects on skin barrier function,metabolic health and stress responses.Methods: We supplemented the diets of Chinese adults presenting with hair loss and high risk of metabolic syndrome (n = 26, male gender 38.5%, age = 33.6 ± 4.5 years) with a multi-strain probiotic formula at a dosage of 18.1 billion colony forming units (CFU) twice daily for 12 weeks. We compared the hair density, hair loss, anthropometrics measures, blood biochemistry markers, skin biophysical characteristics and stress-associated responses between baseline and the end of the trial.Results: After 12 weeks of probiotic supplementation, 96.2% of the study participants had improvement in hair density (median density level increased: 1; interquartile range: 1-2). Participants reported reduced hair loss both quantitatively and qualitatively. The majority (73.1%) of the participants reported apparent relief of scalp itching. Stratum corneum hydration and pH increased, while transepidermal water loss and sebum decreased on both scalp and facial skin. Body weight and body mass index decreased following probiotic consumption. Most components of glucose metabolism and the lipid profile were significantly better, with increases in high-density lipoprotein cholesterol and reductions in glucose, homeostasis model assessment-estimated insulin resistance, total cholesterol, non-high-density lipoprotein cholesterol and triglycerides. Inflammation and oxidative stress markers improved with increases in interferon-γ and superoxide dismutase, and reductions in high-sensitivity C-reactive protein, interleukin-6, interleukin-31 and malondialdehyde. No changes were observed in glycated hemoglobin, insulin, immunoglobulin E and interleukin-10 levels. Besides, perceived stress relieved in participants accompanied with improved sleep quality as well as better overall perception of life quality and health.Conclusion: Twice-daily supplementation with the test probiotic formula over a 12-weeks period may exert profound beneficial effects on hair growth, skin condition, glucose and lipid metabolism, and stress-associated psychological and physiological responses in participants presenting with hair loss and high risk of metabolic syndrome. This study has been registered at Chinese Clinical Trial Registry (ChiCTR2100050498).Keywords: hair density, hair loss, metabolic syndrome, oral probiotic supplementation

Background: Sacubitril/valsartan (SV) is a novel and effective therapy for heart failure with reduced ejection fraction (HFrEF). Despite several sex-specific particularities that may influence drug effects, there has been no prior study evaluating the safety of SV in women with HFrEF in the “real-world.” Methods: We performed a literature search to identify observational studies evaluating SV. We contacted all authors to obtain sex-specific data on major adverse outcomes. We compared all-cause and cardiovascular (CV) deaths, heart failure hospitalizations, hyperkalemia, and hypotension in men and women. Results: We identified five cohort studies enrolling 8,981 patients; 6,092 men (67.8%) and 2,889 women (32.2%). The mean age was 67 years in both sexes. The rates for all-cause mortality, CV mortality, heart failure hospitalizations, hypotension, and hyperkalemia were similar between women and men. Although the unadjusted aggregate rates of all-cause and CV mortalities were numerically higher in men than in women, these differences did not reach statistical differences. Conclusion: Our meta-analysis showed similar rates of major adverse events in men and women with HFrEF treated with SV. Larger observational studies with longer duration and a higher number of women are needed to confirm the long-term safety of SV in women in the clinical practice. Résumé: Contexte: Le sacubitril/valsartan (SV) est un médicament novateur et efficace contre l’insuffisance cardiaque à fraction d’éjection réduite (ICFER). Malgré le fait que plusieurs particularités sexospécifiques peuvent influencer les effets du médicament, aucune étude préalable n’a été menée pour évaluer l’innocuité du SV chez les femmes atteintes d’ICFER dans la ''vraie vie''. Méthodologie: Nous avons effectué une recherche de la littérature pour recenser les études observationnelles évaluant le SV Nous avons communiqué avec tous les auteurs pour obtenir des données sexospécifiques sur les principaux issus défavorables. Nous avons comparé les données sur les décès toutes causes confondues et les décès d’origine cardiovasculaire (CV), les hospitalisations pour cause d’insuffisance cardiaque, l’hyperkaliémie et l’hypotension tant chez les hommes que chez les femmes. Résultats: Nous avons recensé cinq études de cohortes auxquelles ont participé 8 981 patients, soit 6 092 hommes (67,8 %) et 2 889 femmes (32,2 %). L’âge moyen était de 67 ans chez les patients des deux sexes. Les taux de décès toutes causes confondues, de décès d’origine CV, d’hospitalisation pour cause d’insuffisance cardiaque, d’hypotension et d’hyperkaliémie chez les femmes étaient similaires à ceux notés chez les hommes. Les taux globaux non ajustés de décès toutes causes confondues et de décès d’origine CV étaient numériquement plus élevés chez les hommes que chez les femmes, mais il n’y avait pas de différence sur le plan statistique. Conclusion: Notre méta-analyse a mis en évidence des taux similaires d’événements indésirables majeurs chez les hommes et chez les femmes atteints d’ICFER traités par le SV. Des études observationnelles à plus grande échelle avec de plus longue durée et un nombre plus élevé de femmes devront être menées pour confirmer l’innocuité à long terme du SV en pratique clinique chez les femmes.

Objectives: In this study, we hypothesized that replacing conventional milk, which contains A1 and A2 β-casein proteins, with milk that contains only A2 β-casein in the diet of dairy or milk-intolerant preschoolers (age 5 to 6 years) would result in reduced gastrointestinal symptoms associated with milk intolerance, and that this would correspond with cognitive improvements. Methods: This randomized, double-blind, crossover study aimed to compare the effects of 5 days’ consumption of conventional milk versus milk containing only A2 β-casein on gastrointestinal symptoms, as assessed via visual analog scales, average stool frequency and consistency, and serum inflammatory and immune biomarkers in healthy preschoolers with mild-to-moderate milk intolerance. The study also aimed to compare changes in the cognitive behavior of preschoolers, based on Subtle Cognitive Impairment Test scores. Results: Subjects who consumed milk containing only A2 β-casein had significantly less severe gastrointestinal symptoms as measured by visual analog scales, reduced stool frequency, and improvements in stool consistency, compared with subjects consuming conventional milk. There were significant increases from baseline in serum interleukin-4, immunoglobulins G, E, and G1, and beta-casomorphin-7 coupled to lower glutathione levels, in subjects consuming conventional milk compared with milk containing only A2 β-casein. Subtle Cognitive Impairment Test analysis showed significant improvements in test accuracy after consumption of milk containing only A2 β-casein. There were no severe adverse events related to consumption of either milk product. Conclusions: Replacing conventional milk with milk containing only A2 β-casein reduced gastrointestinal symptoms associated with milk intolerance in Chinese preschool children, with corresponding improvements in aspects of cognitive performance.

Purpose We assessed the validity of postsurgery venous thromboembolism (VTE) diagnoses identified from administrative databases and compared Bayesian and multiple imputation (MI) approaches in correcting for outcome misclassification in logistic regression models. Methods Sensitivity and specificity of postsurgery VTE among patients undergoing total hip or knee replacement (THR/TKR) were assessed against chart review in six Montreal hospitals in 2009 to 2010. Administrative data on all THR/TKR Quebec patients in 2009 to 2010 were obtained. The performance of Bayesian external, Bayesian internal, and MI approaches to correct the odds ratio (OR) of postsurgery VTE in tertiary versus community hospitals was assessed using simulations. Bayesian external approach used prior information from external sources, while Bayesian internal and MI approaches used chart review. Results In total, 17 319 patients were included, 2136 in participating hospitals, among whom 75 had VTE in administrative data versus 81 in chart review. VTE sensitivity was 0.59 (95% confidence interval, 0.48-0.69) and specificity was 0.99 (0.98-0.99), overall. The adjusted OR of VTE in tertiary versus community hospitals was 1.35 (1.12-1.64) using administrative data, 1.45 (0.97-2.19) when MI was used for misclassification correction, and 1.53 (0.83-2.87) and 1.57 (0.39-5.24) when Bayesian internal and external approaches were used, respectively. In simulations, all three approaches reduced the OR bias and had appropriate coverage for both nondifferential and differential misclassification. Conclusion VTE identified from administrative data had low sensitivity and high specificity. The Bayesian external approach was useful to reduce outcome misclassification bias in logistic regression; however, it required accurate specification of the misclassification properties and should be used with caution.

Background: The effect of menopausal status on the risk factors of cardiovascular (CV) disease is not well ascertained. We aimed to evaluate the impact of menopause on several traditional and non-traditional cardiovascular (CV) risk factors. Methods: The CARTaGENE study was a prospective cohort study with random sampling of individuals in Quebec, Canada. We completed a seven-year follow-up in 2016. For this analysis, we included only subjects without prior cardiovascular (CV) events (CVE) or CV interventions (CVI). We defined the primary endpoint as CVE which can be any of the following events: acute coronary syndromes, heart failure, strokes, CV deaths, and peripheral vascular events. The secondary endpoint was CVI which included coronary, carotid, or peripheral artery revascularization. We used Cox proportional hazard stepwise multivariate analyses to identify independent predictors of the primary endpoint separately in pre- and post-menopausal women. Results Of 9,529 women without prior CV disease, 57% were post-menopausal. The mean age was 47.4 years and 58.6 years for pre-menopausal and post-menopausal women, respectively. There were 793 CVEs and 83 CVIs with a median time to event of 6.6 years. Hypertension, active smoking, increased waist to hip ratio, and glycosylated hemoglobin were independent predictors of the primary endpoint in both pre- and post-menopausal women. Furthermore, advanced age, family history of myocardial infarction, prior cancer, increased gamma-glutamyl transferase, and hyperuricemia also predicted increased riks of the primary endpoint in post-menopausal women. Conclusion: Hypertension, active smoking, increased waist to hip ratio, and high glycosylated hemoglobin were associated with increased CV risk in pre-menopausal women. The impact of hypertension was markedly amplified in pre-menopausal women compared to postmenopausal women. Intensive blood pressure control should be considered in pre-menopausal women.

Background: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk for developing heart failure (HF), and clinical models are needed to identify patients with a greater risk for HF hospitalization (HHF). The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM) was recently developed and validated to predict HHF in patients with T2DM in two large clinical trials (SAVOR-TIMI 53 and DECLARE-TIMI 58). We aimed to validate the TRS-HFDM in another cohort of patients with T2DM. Methods: We validated the TRS-HFDM score in 5,123 patients with T2DM for fatal or non-fatal HHF in the placebo arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes Study Group). The TRS-HFDM included: prior HF, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. We evaluated discrimination with the Harrell C index, and calibration by comparing observed event rates for HHF with predicted risk, and the Nam-D’Agostino statistic. Results: During a mean follow up of 4.8 years, 212 patients (4.14%) experienced at least one HHF. The mean age was 63 ±6.7 years, and 38% were female. The baseline hemoglobin A1C was 8.3%, and 36% were on insulin. The ACCORD patients had less comorbidities with a lower proportion of patients with renal dysfunction (8% vs. 16% vs. 17%), established cardiovascular disease (35% vs.79% vs. 41%) and pre-existing HF (5% vs. 13% vs. 10%) compared to patients enrolled in the SAVOR-TIMI 53 and DECLARE TIMI-58 trials respectively. In our cohort, the TRS-HFDM score predicted well HHF events with a Harrel C index of 0.78. The integer-based score was well calibrated, with the observed Kaplan-Meier HHF rates closely predicting the Kaplan-Meier event rates at the end follow up (Nam D`Agostino test: 65.39 (p Discussion: Our findings confirm the applicability of the TRS-HFDM in a large cohort of patients with T2DM with less high-risk features than the SAVOR-TIMI 53 and DECLARE-TIMI 58 populations. Future validation of this risk score in observational cohort studies is needed to evaluate its external validity in a general clinical setting.

Objective Outcome misclassification may occur in observational studies using administrative databases. We evaluated a two-step multiple imputation approach based on complementary internal validation data obtained from two subsamples of study participants to reduce bias in hazard ratio (HR) estimates in Cox regressions. Methods We illustrated this approach using data from a surveyed sample of 6247 individuals in a study of statin-diabetes association in Quebec. We corrected diabetes status and onset assessed from health administrative data against self-reported diabetes and/or elevated fasting blood glucose (FBG) assessed in subsamples. The association between statin use and new onset diabetes was evaluated using administrative data and the corrected data. By simulation, we assessed the performance of this method varying the true HR, sensitivity, specificity, and the size of validation subsamples. Results The adjusted HR of new onset diabetes among statin users versus non-users was 1.61 (95% confidence interval: 1.09–2.38) using administrative data only, 1.49 (0.95–2.34) when diabetes status and onset were corrected based on self-report and undiagnosed diabetes (FBG ≥ 7 mmol/L), and 1.36 (0.92–2.01) when corrected for self-report and undiagnosed diabetes/impaired FBG (≥ 6 mmol/L). In simulations, the multiple imputation approach yielded less biased HR estimates and appropriate coverage for both non-differential and differential misclassification. Large variations in the corrected HR estimates were observed using validation subsamples with low participation proportion. The bias correction was sometimes outweighed by the uncertainty introduced by the unknown time of event occurrence. Conclusion Multiple imputation is useful to correct for outcome misclassification in time-to-event analyses if complementary validation data are available from subsamples. Copyright © 2017 John Wiley & Sons, Ltd.

We aimed to develop an artificial intelligence (AI) based electrocardiogram (ECG) algorithm to screen patients for DM. A convolutional neural network was used to identify diabetes using ECG signal data in the CARTeGENE registry (population-based study in Quebec, Canada). In the registry, 7,460

It remains unclear whether black and white women with acute coronary syndromes (ACS) have similar short-term mortality. We completed a meta-analysis comparing the short-term mortality of black women to white women with ACS. We completed an extensive literature search from January 1987 to February

Outcome misclassification may occur in observational studies using administrative databases. We evaluated a two-step multiple imputation approach based on complementary internal validation data obtained from two subsamples of study participants to reduce bias in hazard ratio (HR) estimates in Cox regressions.We illustrated this approach using data from a surveyed sample of 6247 individuals in a study of statin-diabetes association in Quebec. We corrected diabetes status and onset assessed from health administrative data against self-reported diabetes and/or elevated fasting blood glucose (FBG) assessed in subsamples. The association between statin use and new onset diabetes was evaluated using administrative data and the corrected data. By simulation, we assessed the performance of this method varying the true HR, sensitivity, specificity, and the size of validation subsamples.The adjusted HR of new onset diabetes among statin users versus non-users was 1.61 (95% confidence interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when diabetes status and onset were corrected based on self-report and undiagnosed diabetes (FBG ≥ 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report and undiagnosed diabetes/impaired FBG (≥ 6 mmol/L). In simulations, the multiple imputation approach yielded less biased HR estimates and appropriate coverage for both non-differential and differential misclassification. Large variations in the corrected HR estimates were observed using validation subsamples with low participation proportion. The bias correction was sometimes outweighed by the uncertainty introduced by the unknown time of event occurrence.Multiple imputation is useful to correct for outcome misclassification in time-to-event analyses if complementary validation data are available from subsamples. Copyright © 2017 John WileySons, Ltd.

The long-term residual risks for cardiovascular (CV) events among individuals taking statins for primary prevention remain unclear. Our objective was to determine the long-term rates and predictors of CV interventions (CVI) and CV events (CVE) in statin users for primary CV prevention. The

This study reports the plasma glutathione concentrations in a double-blind, randomized, controlled, 2 × 2 cross-over study in which healthy participants consumed conventional milk (2 × 250 mL per day) containing both A1 and A2 types of β-casein, or milk containing only A2 type β-casein. Beta-casomorphin-7 (BCM-7), a peptide uniquely derived from the A1 type of β-casein, was previously reported to downregulate glutathione expression in human gut epithelial and neuronal cell lines by limiting cysteine uptake. The current human study demonstrates that consumption of milk containing only A2 β-casein was associated with a greater increase in plasma glutathione concentrations compared with the consumption of milk containing both β-casein types, and did not increase plasma BCM-7 concentrations compared with the washout diet in the study participants. Thus, milk containing only A2 β-casein and not A1 β-casein has the potential to promote the production of the antioxidant glutathione in humans. Clinical Trial Registration ClinicalTrials.gov; identifier: NCT02406469 Electronic supplementary material The online version of this article (doi:10.1186/s12937-016-0201-x) contains supplementary material, which is available to authorized users.

International audience; Background: Dietary fibers have been associated with a reduction in appetite and energy intake. Although a few studies suggest that nonviscous fibers can exert such effects, likely through colonic fermentation, limited data are available. Objective: The objective of this study was to determine whether alpha-galacto-oligosaccharides (alpha-GOSs), fermentable soluble fibers extracted from legumes, could reduce appetite, food intake, and inflammation in overweight subjects. Methods: In 2 single-center, double-blind, randomized, placebo-controlled trials, 88 overweight adults [50% men and 50% women; 18-60 y old; body mass index (in kg/m(2)): 25-28] were supplemented for 14 d with tea that contained alpha-GOSs with different alpha-GOS dosages (6, 12, or 18 g alpha-GOSs/d), formulas (12 g alpha-GOSs/d with > 80% of molecules with a degree of polymerization of 2, 3, or 4), or a control substance (glucose syrup). Appetite scores (5 appetite dimensions were assessed on visual analog scales during a preload test meal), food intake (test meal and 24-h food recall), and inflammatory markers [plasma lipopolysaccharide (LPS) and C-reactive protein (CRP)] were evaluated at day 0 (baseline) and day 15. Results: Changes in appetite scores from day 0 to day 15 were significantly higher after alpha-GOS intake, with areas under the curve for the satiety score of + 121 +/- 108, +218 +/- 218, and +306 +/- 205 score . min for 6, 12, and 18 g alpha-GOSs/d, respectively, and -5 +/- 64 score . min for the control group. We observed dose-dependent effects that did not vary by alpha-GOS composition. The administration of 6, 12, or 18 g alpha-GOSs/d significantly and dose-dependently increased the change in energy intake from day 0 to day 15 during a test meal (-13 +/- 19, -26 +/- 22, and -32 +/- 22 kcal, respectively; +6 +/- 21 kcal for the control group). Reductions in energy intake during lunch and dinner were also higher in the alpha-GOS groups in the dose-effect study. At day 15, LPS was dose-dependently reduced without an association with alpha-GOS composition (0.16 +/- 0.02, 0.12 +/- 0.08, and 0.08 +/- 0.05 EU/mL for 6, 12, and 18 g alpha-GOSs/d, respectively, and 0.06 +/- 0.04 EU/mL for the control group) and CRP was significantly lower in the alpha-GOS groups than in the control group in the formulation-effect study. Conclusions: Consumption of alpha-GOSs for 14 d dose-dependently reduced appetite, food intake, and inflammation in overweight adults with no impact of alpha-GOS composition. Consequently, alpha-GOSs appear to promote long-term weight loss and mitigate metabolic disorders.

Ethnopharmacological relevance Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb in Uighur medicine in China, and it is traditionally used for treatment of cough and asthma.The aim of the present study is to evaluate the antitussive, expectorant and bronchodilating effects of extract and fractions (alkaloids and flavonoids) from APP, and to support its folk use with scientific evidence, and lay a foundation for its further researches. Materials and methods APP was extracted with 50% ethanol by reflux, extracts were concentrated in vacuum to afford total extract of APP (EXT). EXT was separated to provide alkaloid fraction (ALK) and flavonoid fraction (FLA) by macroporous resin. Antitussive evaluations were carried out with cough models in mice and guinea pigs induced by ammonia liquor, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity. Bronchodilating activities were evaluated with a bronchoconstrictive challenge induced by acetylcholine chloride and histamine in guinea pigs. Results In all the three antitussive tests, the EXT and ALK could significantly inhibit the frequency of cough, and prolong the cough latent period in animals. High dose of EXT (1650 mg/kg) and ALK (90 mg/kg) in mice and in guinea pigs created therapeutic activities as good as that of codeine phosphate (30 mg/kg). EXT could significantly increase phenol red secretion in mice for 0.64, 1.08 and 1.29 fold averagely at dosages of 183, 550, and 1650 mg/kg, ALK for 0.63, 0.96, 1.06 fold averagely at dosages of 10, 30, and 90 mg/kg, and ammonium chloride (1500 mg/kg, standard expectorant drug) for 0.97 fold, comparing with control group. Aminophylline could dramatically prolong the preconvulsive time for 162.28% in guinea pigs, EXT for 67.34%, 101.96% and 138.00% at dosages of 183, 550, and 1650 mg/kg, ALK for 55.47%, 97.74% and 126.77% at dosages of 10, 30, and 90 mg/kg, and FLA for 84.69%, 95.94% and 154.52% at dosages of 10, 30, and 90 mg/kg, comparing with pretreatment. Conclusions APP is an effective traditional folk medicine for the treatment of cough with potent antitussive, expectorant and bronchodilating activities. The alkaloid fraction is proved to be the most effective components of APP. The alkaloids from APP may be valuable lead compounds for drug development of respiratory diseases.

Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU(®) Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU(®) Restore probiotic 1.70×10(10) CFU (high-dose, n=168), HOWARU(®) Restore probiotic 4.17×10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.

Background Cows’ milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance. Methods Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events. Results Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects. Conclusions Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein. Trial registration ClinicalTrials.gov/NCT02406469 Electronic supplementary material The online version of this article (doi:10.1186/s12937-016-0147-z) contains supplementary material, which is available to authorized users.