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1.
Appetite ; 152: 104711, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32283186

RESUMO

Food cravings are a desire for specific foods which, if uncontrolled may lead to excess energy intake and weight gain. However, information on the relation between food cravings, dietary intake, and indices of metabolic health is limited. This study used baseline data from females (n = 229; aged 40.9 ± 0.7 years; BMI 34.7 ± 6.4 kg/m2) who were dependents of active duty and retired military personnel, and enrolled in the Healthy Families Healthy Forces weight loss and maintenance study. Measures obtained included food cravings using the Food Craving Questionnaire-Trait (which provides a habitual and stable measure of food cravings), dietary composition and eating patterns from three 24-h dietary recalls and the Stanford 7-day Physical Activity Recall, body composition from anthropometric measures, cardiometabolic risk factors from blood measures, and demographic information from questionnaires. Linear, quantile, or logistic regression models were used to examine the association of total food craving scores on dietary intake, and indices of metabolic health. In individuals reporting plausible energy intake (n = 146; 2210 ± kcals/day) higher food craving scores were associated with a lower diet quality (P < 0.05), higher eating frequency (P = 0.02), longer daily eating interval (P < 0.05), and a lower likelihood of following a time restricted eating pattern (P = 0.02). Food cravings were also positively associated with BMI (P = 0.03) and waist circumference (P = 0.01), but not with measures of cardiometabolic risk (LDL, HDL, total cholesterol:HDL, triglycerides, glucose, glycated hemoglobin, insulin and C-reactive protein concentrations, blood pressure, metabolic syndrome). Our findings of significant associations of food cravings with lower diet quality, poor eating patterns, and unfavorable body composition strongly support efforts of targeting cravings in behavioral programs for weight management.

2.
J Nutr ; 150(2): 404-410, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586209

RESUMO

BACKGROUND: Quick-service restaurants (QSRs) serve one-third of US children on any given day, yet no methods can directly measure energy (kcal) consumed in QSRs. Weighed plate waste is one feasible option, but the accuracy is unknown. OBJECTIVE: The objective of this study was to determine the accuracy of weighed plate waste for measuring children's energy consumption in QSRs. METHODS: Children's plate waste (entrées and sides) was collected for a larger study assessing a community-wide health messaging campaign to inform parents' orders for children in QSRs; a subsample (n = 194) was used for validation. Gross energy left over estimated by weighed plate waste combined with restaurant-stated nutrition information was compared to gross energy determined by bomb calorimetry, the gold-standard energy assessment technique. Analyses were conducted at the meal level (all food items, combined) and stratified by the number of items per meal (1, 2, or 3). Pearson correlations and paired t tests analyzed agreement; Bland-Altman statistics examined differences between energy estimations for the total and stratified subsample. RESULTS: Overall, significant agreement was observed between weighed plate waste and bomb calorimetry (r = 0.99, P < 0.001). On average, weighed plate waste underestimated energy content by <2 kcal compared with bomb calorimetry (mean percent difference ± SD of 0.3% ± 10.7%); 94% of estimations fell within the limits of agreement (-23.5 to 26.8 kcal), and 63% and 24% of estimations differed by <10 or <20 net kcal, respectively. Although stratification by item number showed slight variation, mean differences for all strata were <5 kcal (t test P > 0.80), suggesting the accuracy of weighed plate waste for measuring meals of various sizes. CONCLUSIONS: Weighed plate waste is an accurate and valid field technique for measuring children's energy consumption from food in QSRs. Future improvements to capturing beverages, self-serve condiments, and sharing behaviors may improve the overall feasibility and accuracy.

3.
Lancet Diabetes Endocrinol ; 7(9): 673-683, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31303390

RESUMO

BACKGROUND: For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals. METHODS: CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m2) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193. FINDINGS: From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes. INTERPRETATION: 2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits. FUNDING: National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

4.
Nutrients ; 11(6)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216640

RESUMO

Environmental factors such as food availability and variety can function as cues for overeating in individuals susceptible to overweight or obesity, but relatively little is known about other types of environmental factors that may also be important. This qualitative study compared and contrasted categories of internal and external cues through focus groups and key informant interviews with 24 adults (26 to 77 years old) in the United States who had a body mass index within the healthy range (21.6 ± 2.5 kg/m2) or had overweight or obesity (29.1 ± 3.6 kg/m2). Five domains of external factors influencing food intake were identified: (a) Environmental cues including food availability and variety; (b) normative expectations for dietary intake; (c) food palatability; (d) overt social pressures to overeat; and (e) perceived social expectations around eating. All external domains were noted by participants with overweight or obesity to be challenging, and solutions to avoid overeating were lacking; however, overt social pressures and perceived social expectations appeared to be especially problematic. By explicitly defining different domains of external factors that challenge healthy weight regulation, this study identifies specific targets to address in interventions for healthy weight management.


Assuntos
Ingestão de Alimentos/psicologia , Comportamento Alimentar/psicologia , Obesidade/psicologia , Sobrepeso/psicologia , Adulto , Idoso , Sinais (Psicologia) , Ingestão de Energia , Meio Ambiente , Feminino , Humanos , Hiperfagia/psicologia , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
5.
Mil Med ; 184(11-12): 647-652, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132088

RESUMO

INTRODUCTION: Effective, standardized, and easily accessible weight management programs are urgently needed for military beneficiaries. Videoconference interventions have the potential for widespread scaling, and can provide both real time interaction and flexibility in delivery times regardless of location, but there is little information on their effectiveness and acceptability. MATERIALS AND METHODS: This study as part of a larger weight loss trial describes the videoconference adaption of Group Lifestyle Balance (GLB) program, a community group-based Diabetes Prevention Program intervention, and provides a comparison of weight loss and meeting attendance between in-person and videoconference delivery modes over 12 weeks in adult family members of military service members. Forty-three participants were enrolled from two military installations and received either the videoconference-adapted or an in-person GLB program in a non-randomized trial design. Differences in program attendance and percent weight lost at 12 weeks were compared by independent samples t-tests and nonparametric methods. Group differences in the percentage of weight lost over the 12-week period were analyzed using a linear mixed model. RESULTS: All GLB intervention components were successfully delivered by videoconference with minor adaptations for the different delivery mechanism. Participant retention was 70% and 96% in the in-person and videoconference groups, respectively (p = 0.04). Completing participants in both groups lost a significant percent body weight over the 12 week intervention (p < 0.001) and there was no difference in percent body weight after 12 weeks of intervention (6.2 ± 3.2% and 5.3 ± 3.4% for in-person and videoconference at 12 weeks, respectively; p = 0.60). CONCLUSION: This study describes the first videoconference adaption of the GLB program for use in military families. Attrition was lower in the videoconference group, and there were a similar levels of weight loss in both groups regardless of delivery modality. Videoconference weight loss interventions are effective and feasible for scaling to support healthy weight management in military as well as civilian populations.

6.
J Acad Nutr Diet ; 119(6): 923-933, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826304

RESUMO

BACKGROUND: US national survey data shows fast food accounted for 11% of daily caloric intake in 2007-2010. OBJECTIVE: To provide a detailed assessment of changes over time in fast-food menu offerings over 30 years, including food variety (number of items as a proxy), portion size, energy, energy density, and selected micronutrients (sodium, calcium, and iron as percent daily value [%DV]), and to compare changes over time across menu categories (entrées, sides, and desserts). DESIGN: Fast-food entrées, sides, and dessert menu item data for 1986, 1991, and 2016 were compiled from primary and secondary sources for 10 popular fast-food restaurants. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Linear mixed-effects analysis of variance was performed to examine changes over time by menu category. RESULTS: From 1986 to 2016, the number of entrées, sides, and desserts for all restaurants combined increased by 226%. Portion sizes of entrées (13 g/decade) and desserts (24 g/decade), but not sides, increased significantly, and the energy (kilocalories) and sodium of items in all three menu categories increased significantly. Desserts showed the largest increase in energy (62 kcal/decade), and entrées had the largest increase in sodium (4.6% DV/decade). Calcium increased significantly in entrées (1.2%DV/decade) and to a greater extent in desserts (3.9% DV/decade), but not sides, and iron increased significantly only in desserts (1.4% DV/decade). CONCLUSIONS: These results demonstrate broadly detrimental changes in fast-food restaurant offerings over a 30-year span including increasing variety, portion size, energy, and sodium content. Research is needed to identify effective strategies that may help consumers reduce energy intake from fast-food restaurants as part of measures to improve dietary-related health issues in the United States.

7.
Am J Health Promot ; 33(1): 118-130, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29807441

RESUMO

PURPOSE: Programs focused on employee well-being have gained momentum in recent years, but few have been rigorously evaluated. This study evaluates the effectiveness of an intervention designed to enhance vitality and purpose in life by assessing changes in employee quality of life (QoL) and health-related behaviors. DESIGN: A worksite-based randomized controlled trial. SETTING: Twelve eligible worksites (8 randomized to the intervention group [IG] and 4 to the wait-listed control group [CG]). PARTICIPANTS: Employees (n = 240) at the randomized worksites. INTERVENTION: A 2.5-day group-based behavioral intervention. MEASURES: Rand Medical Outcomes Survey (MOS) 36-item Short-Form (SF-36) vitality and QoL measures, Ryff Purpose in Life Scale, Center for Epidemiologic Studies questionnaire for depression, MOS sleep, body weight, physical activity, diet quality, and blood measures for glucose and lipids (which were used to calculate a cardiometabolic risk score) obtained at baseline and 6 months. ANALYSIS: General linear mixed models were used to compare least squares means or prevalence differences in outcomes between IG and CG participants. RESULTS: As compared to CG, IG had a significantly higher mean 6-month change on the SF-36 vitality scale ( P = .003) and scored in the highest categories for 5 of the remaining 7 SF-36 domains: general health ( P = .014), mental health ( P = .027), absence of role limitations due to physical problems ( P = .026), and social functioning ( P = .007). The IG also had greater improvements in purpose in life ( P < .001) and sleep quality (index I, P = .024; index II, P = .021). No statistically significant changes were observed for weight, diet, physical activity, or cardiometabolic risk factors. CONCLUSION: An intensive 2.5-day intervention showed improvement in employee QoL and well-being over 6 months.


Assuntos
Promoção da Saúde/métodos , Saúde do Trabalhador , Educação , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Qualidade de Vida , Inquéritos e Questionários , Local de Trabalho
8.
BMJ ; 363: k4864, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541752

RESUMO

OBJECTIVE: To measure the energy content of frequently ordered meals from full service and fast food restaurants in five countries and compare values with US data. DESIGN: Cross sectional survey. SETTING: 223 meals from 111 randomly selected full service and fast food restaurants serving popular cuisines in Brazil, China, Finland, Ghana, and India were the primary sampling unit; 10 meals from five worksite canteens were also studied in Finland. The observational unit was frequently ordered meals in selected restaurants. MAIN OUTCOME MEASURE: Meal energy content, measured by bomb calorimetry. RESULTS: Compared with the US, weighted mean energy of restaurant meals was lower only in China (719 (95% confidence interval 646 to 799) kcal versus 1088 (1002 to 1181) kcal; P<0.001). In analysis of variance models, fast food contained 33% less energy than full service meals (P<0.001). In Finland, worksite canteens provided 25% less energy than full service and fast food restaurants (mean 880 (SD 156) versus 1166 (298); P=0.009). Country, restaurant type, number of meal components, and meal weight predicted meal energy in a factorial analysis of variance (R2=0.62, P<0.001). Ninety four per cent of full service meals and 72% of fast food meals contained at least 600 kcal. Modeling indicated that, except in China, consuming current servings of a full service and a fast food meal daily would supply between 70% and 120% of the daily energy requirements for a sedentary woman, without additional meals, drinks, snacks, appetizers, or desserts. CONCLUSION: Very high dietary energy content of both full service and fast food restaurant meals is a widespread phenomenon that is probably supporting global obesity and provides a valid intervention target.


Assuntos
Ingestão de Energia , Fast Foods/análise , Análise de Alimentos/estatística & dados numéricos , Refeições , Análise de Variância , Brasil , China , Comportamento do Consumidor , Estudos Transversais , Análise Fatorial , Finlândia , Gana , Humanos , Índia , Necessidades Nutricionais , Restaurantes , Estados Unidos
9.
Nutrients ; 10(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513876

RESUMO

Gluten-free (GF) eating patterns are frequently perceived to be healthier than gluten-containing (GC) ones, but there has been very little research to evaluate this viewpoint. The effect of GF eating patterns on dietary composition was assessed using two independent approaches. One approach compared macronutrients and typical shortfall nutrients between MyPlate example menus developed with either GC or equivalent GF foods. In this analysis, the GF menus were significantly lower in protein, magnesium, potassium, vitamin E, folate, and sodium (p = 0.002⁻0.03), with suggestive trends towards lower calcium and higher fat (p = 0.06⁻0.08). The second approach was a meta-analysis of seven studies comparing information on the nutrient intakes of adults with celiac disease following a GF diet with control subjects eating a GC diet, and differences were evaluated using paired t-tests or Wilcoxon Signed rank tests. In this analysis, consuming a GF diet was associated with higher energy and fat intakes, and lower fiber and folate intakes compared to controls (p < 0.001 to p = 0.03). After adjusting for heterogeneity and accounting for the large mean effect size (-0.88 ± 0.09), the lower fiber remained significant (p < 0.001). These combined analyses indicate that GF diets are not nutritionally superior except for sodium, and in several respects are actually worse.


Assuntos
Dieta Livre de Glúten , Valor Nutritivo , Adulto , Doença Celíaca/dietoterapia , Alimentos Especializados , Humanos , Refeições , Estado Nutricional
11.
Obesity (Silver Spring) ; 26 Suppl 2: S16-S24, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29575782

RESUMO

BACKGROUND: The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments. OBJECTIVES: The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity-related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high-priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self-monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed. SIGNIFICANCE: Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field.


Assuntos
Obesidade/terapia , Adulto , Peso Corporal , Ingestão de Alimentos/psicologia , Exercício Físico , Humanos , Obesidade/psicologia , Sono , Perda de Peso
12.
Nutr Metab (Lond) ; 15: 12, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29445415

RESUMO

Background: Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur's bioavailability and efficacy, may be candidate agents for controlling body fat, metabolism and low grade inflammation. Methods: 47 eight-week-old male C57BL/6 mice were fed a high fat diet (HFD) for 23 weeks to induce obesity. Then, mice were divided into 5 groups. Group 1 continued on HFD ad libitum. The other 4 groups underwent CR (reduced 10% HFD intake for 10 weeks, 20% for 20 weeks) with Cur, Pip, Cur + Pip or none of these. Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-γ, interleukin (IL)-10, IL-12 p70, IL-1ß, IL-6 and KC/GRO), plasma Cur metabolites and liver telomere length were measured. Results: Compared to the other groups, obese mice who underwent CR and received Cur + Pip in their diet lost more fat and had significantly lower IL-1ß and KC/GRO. Tandem mass spectrometry analysis of plasma from obese mice under CR showed no difference in Cur metabolite levels between groups supplemented with Cur alone or combined with Pip. However, plasma IL-1ß levels were inversely correlated with curcumin glucuronide. Minor modulation of telomere length were observed. Conclusions: It is plausible that supplementing the high fat diet of CR mice with Cur + Pip may increase loss of body fat and suppresses HFD induced inflammation. Combination of Cur and Pip has potential to enhance CR effects for the prevention of metabolic syndrome.

13.
ACS Med Chem Lett ; 9(12): 1217-1222, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30613329

RESUMO

In solving the P-gp and BCRP transporter-mediated efflux issue in a series of benzofuran-derived pan-genotypic palm site inhibitors of the hepatitis C virus NS5B replicase, it was found that close attention to physicochemical properties was essential. In these compounds, where both molecular weight (MW >579) and TPSA (>110 Å2) were high, attenuation of polar surface area together with weakening of hydrogen bond acceptor strength of the molecule provided a higher intrinsic membrane permeability and more desirable Caco-2 parameters, as demonstrated by trifluoroacetamide 11 and the benchmark N-ethylamino analog 12. In addition, the tendency of these inhibitors to form intramolecular hydrogen bonds potentially contributes favorably to the improved membrane permeability and absorption. The functional group minimization that resolved the efflux problem simultaneously maintained potent inhibitory activity toward a gt-2 HCV replicon due to a switching of the role of substituents in interacting with the Gln414 binding pocket, as observed in gt-2a NS5B/inhibitor complex cocrystal structures, thus increasing the efficiency of the optimization. Noteworthy, a novel intermolecular S=O···C=O n → π* type interaction between the ligand sulfonamide oxygen atom and the carbonyl moiety of the side chain of Gln414 was observed. The insights from these structure-property studies and crystallography information provided a direction for optimization in a campaign to identify second generation pan-genotypic NS5B inhibitors.

14.
Med Sci Sports Exerc ; 49(11): 2240-2249, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29045325

RESUMO

PURPOSE: Calorie restriction (CR) improves health span and delays age-related diseases in many species. The multicenter Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was the first randomized controlled trial of CR in nonobese humans. The aim of this investigation was to determine the effects of CR on V˙O2max and muscle strength in the CALERIE trial. METHODS: Healthy, normal-weight, and mildly overweight women and men (n = 218, mean ± SE age = 37.9 ± 0.5 yr) were randomized to 25% CR or an ad libitum (AL) control condition in a 2:1 allocation (143 CR, 75 AL). V˙O2max was determined with an incremental treadmill test; the strength of the knee flexors and extensors was assessed by dynamometry at baseline, 1 yr, and 2 yr. RESULTS: The CR group achieved an average 11.9% ± 0.7% CR during the 2-yr intervention. Body weight decreased in CR (-7.7 ± 0.4 kg), but not AL (+0.2 ± 0.5 kg). Absolute V˙O2max (L·min) decreased at 1 and 2 yr with CR, whereas V˙O2max expressed relative to body mass increased at both time points (1 yr: +2.2 ± 0.4; 2 yr: +1.9 ± 0.5 mL·kg·min) and relative to AL. The CR group increased their treadmill test time and workload at 1 and 2 yr. Strength results in CR were similar, with decreases in absolute flexor and extensor strength, but increases when expressed relative to body mass. No changes were observed for V˙O2max expressed relative to lean body mass or leg lean mass. CONCLUSIONS: Two years of modest CR without a structured exercise component did not appear to compromise aerobic capacity in healthy nonobese adults. The clinical implications of the observed changes in V˙O2max and muscle strength will be important to explore in future studies.


Assuntos
Restrição Calórica , Força Muscular/fisiologia , Consumo de Oxigênio/fisiologia , Adulto , Índice de Massa Corporal , Proteínas na Dieta/administração & dosagem , Teste de Esforço , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Resistência Física/fisiologia , Perda de Peso , Adulto Jovem
15.
Am J Clin Nutr ; 106(3): 947-948, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28864576
16.
Am J Clin Nutr ; 106(4): 1052-1061, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28814395

RESUMO

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined.Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation.Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8.Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation.Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394.


Assuntos
Citocinas/sangue , Dieta , Fezes/química , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Vitamina K 2/metabolismo , Grãos Integrais , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Citocinas/metabolismo , Fezes/microbiologia , Comportamento Alimentar , Feminino , Manipulação de Alimentos , Humanos , Inflamação/sangue , Intestinos/microbiologia , Masculino , Pessoa de Meia-Idade , Necessidades Nutricionais , Vitamina K/metabolismo , Vitamina K 2/sangue
17.
ACS Med Chem Lett ; 8(7): 771-774, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28740615

RESUMO

Iterative structure-activity analyses in a class of highly functionalized furo[2,3-b]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (14) is described.

18.
Bioorg Med Chem Lett ; 27(15): 3294-3300, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28633899

RESUMO

The synthesis, structure-activity relationship (SAR) data, and further optimization of the metabolic stability and pharmacokinetic (PK) properties for a previously disclosed class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors are described. These efforts led to the discovery of BMS-961955 as a viable contingency backup to beclabuvir which was recently approved in Japan for the treatment of HCV as part of a three drug, single pill combination marketed as XimencyTM.


Assuntos
Antivirais/química , Antivirais/farmacologia , Benzazepinas/química , Benzazepinas/farmacologia , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Antivirais/farmacocinética , Benzazepinas/farmacocinética , Cães , Haplorrinos , Hepacivirus/enzimologia , Hepacivirus/metabolismo , Hepatite C/virologia , Humanos , RNA Replicase/antagonistas & inibidores , RNA Replicase/metabolismo , Ratos , Proteínas não Estruturais Virais/metabolismo
19.
Sci Am ; 316(6): 36-41, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28510561
20.
BMC Public Health ; 17(1): 310, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28399838

RESUMO

BACKGROUND: Nutrition clubs (NC) operate in community settings and provide members with nutrition education and meal replacements for weight management. NC are owned and operated by distributors of Herbalife products. There are over 6200 NC in the US, but there has been no independent assessment of the association of these NC with biomarkers of health. METHODS: We conducted a cross-sectional pilot study to compare the health status of 100 NC members to 100 community-matched controls (CC) in the greater Boston area. Each CC was matched to a NC member for community of residence (zip code), age category, gender, BMI category, race/ethnicity, education level (category), and readiness to make health changes. Measures obtained included cardio-metabolic risk factors, body composition, markers of nutritional status, reported health status, dietary intake, physical activity, sleep and depression. RESULTS: Participants were predominantly female (64%) and Hispanic (73%). NC members had significantly lower fasting insulin (P < 0.001) and lower HbA1c (P = 0.008), higher levels of 25 hydroxy-vitamin D (P = 0.001), and vitamin E:cholesterol ratio (P < 0.001), and lower prevalence of metabolic syndrome (P = 0.02) compared to CC. In addition, most of the NC members (99%) were satisfied with Herbalife NC membership for themselves and their families. A higher percentage of NC members (86%) compared to CC (32%) reported being in much better or somewhat better health compared to a year ago (P < 0.001); and they reported significantly better physical health (P = 0.03), and fewer sleep problems (P = 0.03). CONCLUSION: Herbalife NC membership was positively associated with perceived health and measured cardiometabolic benefits. However, causality cannot be inferred from these findings.


Assuntos
Dieta , Nível de Saúde , Apoio Social , Adolescente , Adulto , Fatores Etários , Biomarcadores , Composição Corporal , Índice de Massa Corporal , Boston , Estudos Transversais , Exercício Físico , Jejum , Feminino , Hemoglobina A Glicada/análise , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Projetos Piloto , Fatores Sexuais , Sono , Fatores Socioeconômicos , Adulto Jovem
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