Barriers to USMLE Step-1 accommodations: Students with Type 1 Diabetes.

PURPOSE: Students who earn their medical doctorate (MD) in the U.S. must pass the United States Medical Licensing Exam (USMLE) Step-1. The application process for students with disabilities who seek Step-1 accommodations can be arduous, barrier-ridden, and can impose a significant burden that may have long-lasting effects. We sought to understand the experiences of medical students with Type-1 Diabetes (T1D) who applied for Step-1 accommodations. METHODS: A Qualtrics survey was administered to students enrolled in Liaison Committee on Medical Education (LCME)-accredited MD programs who disclosed having a primary diagnosis of T1D. Basic counts and qualitative inductive analyses were conducted. RESULTS: Of the 21 surveys sent, 16 (76.2%) participants responded. Of the 16 respondents, 11 (68.8%) applied for USMLE Step-1 accommodations, whereas 5 (31.2%) did not. Of the 11 who applied for accommodations, 7 (63.6%) received the accommodations requested, while 4 (36.4%) did not. Of those who received the accommodations requested, 5/7 (71.4%) experienced at least one diabetes-related barrier on exam day. Of those who did not apply for Step-1 accommodations, 4/5 (80%) participants reported experiencing at least one diabetes-related barrier on exam day. Overall, 11/16 (68.8%) students experienced barriers on exam day with or without accommodations. Qualitative analysis revealed themes among participants about their experience with the process: frustration, anger, stress, and some areas of general satisfaction. CONCLUSIONS: This study reports the perceptions of students with T1D about barriers and inequities in the Step-1 accommodations application process. Students with and without accommodations encountered T1D-related obstacles on test day.

Underrepresented Applicants Post-USMLE Pass/Fail: A National Survey of Competitive Residency Directors.

Objective: To report the selection criteria important to residency program directors (PDs) and whether they believe pass/fail scoring will impact underrepresented in medicine (URM), International Medical Graduate (IMG), or osteopathic (DO) residency applicants after the United States Medical Licensing Examination (USMLE) changed Step 1 score reporting to pass/fail in January 2022. Methods: A Qualtrics survey was sent between August 2022 and January 2023 to 1141 US PDs from specialties with traditionally low residency selection rates: dermatology, ophthalmology, otolaryngology, orthopedic surgery, neurosurgery, interventional radiology, diagnostic radiology, radiation oncology, thoracic surgery, vascular surgery, plastic surgery, and urology. Contact information was obtained from AMA, FRIEDA, or program websites. Results: We received 433 responses (38%). When asked to anticipate the difficulty student groups will face matching into their specialty, PDs reported: for URM, 24.0% increased, 46.0% unchanged, and 30.0% decreased; for DO, 49.19% increased, 44.58% unchanged, and 6.23% decreased and for IMG, 56.35% increased, 39.72% unchanged, and 3.93% decreased. When asked to rank the most important selection factors, the top two responses were Step 2 CK score and away rotation participation at their site. Conclusion: PDs overwhelmingly believed residency selection difficulty would either increase or remain unchanged for DO (93.77%) and IMG (96.07%). In contrast, 76.0% reported difficulty for URM students would either decrease or remain unchanged. PDs ranked Step 2 CK score and away rotation participation as the most important selection factors. Despite PDs' belief that the Step 1 pass/fail scoring system may mitigate one barrier for URM students, emphasis on Step 2 CK and away rotations place additional barriers.

Seven-day dietary nitrate supplementation clinically significantly improves basal macrovascular function in postmenopausal women: a randomized, placebo-controlled, double-blind, crossover clinical trial.

Introduction: Cardiovascular disease (CVD) is the leading cause of death in women, with increased risk following menopause. Dietary intake of beetroot juice and other plant-based nitrate-rich foods is a promising non-pharmacological strategy for increasing systemic nitric oxide and improving endothelial function in elderly populations. The purpose of this randomized, placebo-controlled, double-blind, crossover clinical trial was to determine the effects of short-term dietary nitrate (NO3 -) supplementation, in the form of beetroot juice, on resting macrovascular endothelial function and endothelial resistance to whole-arm ischemia-reperfusion (IR) injury in postmenopausal women at two distinct stages of menopause. Methods: Early-postmenopausal [1-6 years following their final menstrual period (FMP), n = 12] and late-postmenopausal (6+ years FMP, n = 12) women consumed nitrate-rich (400 mg NO3 -/70 mL) and nitrate-depleted beetroot juice (approximately 40 mg NO3 -/70 mL, placebo) daily for 7 days. Brachial artery flow-mediated dilation (FMD) was measured pre-supplementation (Day 0), and approximately 24 h after the last beetroot juice (BR) dose (Day 8, post-7-day BR). Consequently, FMD was measured immediately post-IR injury and 15 min later (recovery). Results: Results of the linear mixed-effects model revealed a significantly greater increase in resting FMD with 7 days of BRnitrate compared to BRplacebo (mean difference of 2.21, 95% CI [0.082, 4.34], p = 0.042); however, neither treatment blunted the decline in post-IR injury FMD in either postmenopausal group. Our results suggest that 7-day BRnitrate-mediated endothelial protection is lost within the 24-h period following the final dose of BRnitrate. Conclusion: Our findings demonstrate that nitrate-mediated postmenopausal endothelial protection is dependent on the timing of supplementation in relation to IR injury and chronobiological variations in dietary nitrate metabolism. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT03644472.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

BACKGROUND: Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. METHODS AND RESULTS: HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. CONCLUSIONS: Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

The underappreciated diversity of bile acid modifications.

The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.

One Avocado per Day as Part of Usual Intake Improves Diet Quality: Exploratory Results from a Randomized Controlled Trial.

Background: Few clinical trials have evaluated diet quality change as a predictor of intervention effectiveness. Objectives: The aim of this study was to examine changes in the Healthy Eating Index (HEI)-2015 after a food-based intervention, and assess the associations between HEI-2015 change and intervention effects on cardiometabolic risk-related outcomes. Methods: The Habitual Diet and Avocado Trial was a 26-wk, multicenter, randomized, controlled parallel-arm study. Participants were 1008 individuals aged ≥25 y with abdominal obesity (females ≥ 35 inches; males ≥ 40 inches). The avocado-supplemented diet group was provided 1 avocado per day, and the habitual diet group maintained their usual diet. Change in diet quality was assessed using the HEI-2015 from a single 24-h recall conducted at 4 time points. Mixed models were used for analysis. Results: The avocado-supplemented diet group had a greater increase in the HEI-2015 (4.74 points; 95% CI: 2.93, 6.55) at 26 wk than the habitual diet group. Compared with the habitual diet group, the avocado-supplemented diet group had greater increases in the following HEI-2015 components from baseline: total vegetables (0.99 points; 95% CI: 0.77, 1.21), fatty acid ratio (2.25 points; 95% CI: 1.74, 2.77), sodium (1.03 points; 95% CI: 0.52, 1.55), refined grains (0.82 points; 95% CI: 0.32, 1.31), and added sugars (0.84 points; 95% CI: 0.49, 1.19). No differences in HEI-2015 improvements were observed by race, ethnicity, study site, body mass index, or age category. In the avocado-supplemented diet compared with the habitual diet group, the HEI-2015 increased in females (6.50 points; 95% CI: 4.39, 8.62) but not in males (0.02 points; 95% CI: -3.44, 3.48). Median HEI-2015 change was not associated with intervention-related changes in cardiometabolic disease risk factors. Conclusions: Intake of 1 avocado per day for 26 wk in adults with abdominal obesity increased adherence to the Dietary Guidelines for Americans. Changes in diet quality did not predict changes in risk factors for cardiometabolic disease.This trial was registered at clinicaltrials.gov as NCT03528031 (https://clinicaltrials.gov/study/NCT03528031).

Intake of Pistachios as a Nighttime Snack Has Similar Effects on Short- and Longer-Term Glycemic Control Compared with Education to Consume 1-2 Carbohydrate Exchanges in Adults with Prediabetes: A 12-Wk Randomized Crossover Trial.

BACKGROUND: Nut intake is associated with better glycemic control and lower cardiovascular disease (CVD) risk. It remains unclear if nut intake timing affects glycemic control and CVD risk factors. Intake of pistachios as a nighttime snack may attenuate morning glucose production and lower fasting plasma glucose (FPG). OBJECTIVES: We assessed the effects of a nighttime (after dinner and before bedtime) pistachio snack (57 g/d) on glycemic control markers, vascular health, lipids/lipoproteins, and diet quality compared with education to consume 1-2 carbohydrate (CHO) exchanges (usual care) in individuals with prediabetes. METHODS: A 2-period, randomized crossover trial was conducted. Participants were provided 57 g/d of dry roasted unsalted pistachios (319 kcal; fat 26 g; CHO 16 g; protein 12 g; fiber 6 g) as a nighttime snack or received usual care for 12 wk. Primary (FPG) and secondary outcomes [hemoglobin A1c (HbA1c), insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipids/lipoproteins, vascular health, and Healthy Eating Index-2015 (HEI-2015)] were measured before and after each condition. RESULTS: A total of 66 participants (50.9 ± 11.6 y, FPG: 106.2 ± 6.4 mg/dL) were randomly assigned, and 51 participants completed the trial. No between-condition differences in FPG {0.9 mg/dL [95% confidence interval (CI): -1.2, 3.1]}, HbA1c, insulin, HOMA-IR, lipids/lipoproteins, blood pressure, or vascular health were observed. The HEI-2015 score was higher after the pistachio condition [6.8 points (95% CI: 1.5, 12.1)] than after usual care driven by higher component scores for seafood and plant proteins [2.0 points (95% CI: 1.0, 2.9)], refined grains [2.3 points (95% CI: 1.1, 3.5)], and the fatty acid ratio [1.7 points (95% CI: 0.0, 3.5)]. CONCLUSIONS: In adults with prediabetes, consuming 57 g/d of pistachios as a nighttime snack increased diet quality but had similar effects on glycemic markers, lipids/lipoproteins, blood pressure, and vascular health compared with the usual care comparator. Pistachios may be a healthful alternative to carbohydrate-rich nighttime snacks to increase alignment with Dietary Guidelines for Americans. This trial was registered at clinicaltrials.gov as NCT04056208.

A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and impacts systemic inflammation and experimental atherosclerosis.

Ketogenic diets (KDs) are very high-fat low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. We investigated a very high-fat KD's vascular impact and plasma metabolic signature compared to a non-ketogenic high-fat diet (HFD). Apolipoprotein E deficient (ApoE -/-) mice were fed a KD (%kcal:81:1:18, fat/carbohydrate/protein), a non-ketogenic high-fat diet with half of the fat content (HFD) (%kcal:40:42:18, fat/carbohydrate/protein) for 12 weeks. Plasma samples were used to quantify the major ketone body beta-hydroxybutyrate (BHB) and several pro-inflammatory cytokines (IL-6, MCP-1, MIP-1alpha, and TNF alpha), and to targeted metabolomic profiling by mass spectrometry. In addition, aortic atherosclerotic lesions were quantified ex-vivo by magnetic resonance imaging (MRI) on a 14-tesla system. KD was atherogenic when compared to the control diet, but KD mice, when compared to the HFD group (1) had markedly higher levels of BHB and lower levels of cytokines, confirming the presence of ketosis that alleviated the well-established fat-induced systemic inflammation; (2) displayed significant changes in the plasma metabolome that included a decrease in lipophilic metabolites and an increase in hydrophilic metabolites; (3) had significantly lower levels of several atherogenic lipid metabolites, including phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides; and (4) presented significantly lower aortic plaque burden. KD was atherogenic and was associated with specific metabolic changes but alleviated the fat-induced inflammation and lessened the progression of atherosclerosis when compared to the HFD.

Using Herbs/Spices to Enhance the Flavor of Commonly Consumed Foods Reformulated to Be Lower in Overconsumed Dietary Components Is an Acceptable Strategy and Has the Potential to Lower Intake of Saturated Fat and Sodium: A National Health and Nutrition Examination Survey Analysis and Blind Tasting.

BACKGROUND: Foods lower in saturated fat, sodium, and added sugars (ie, overconsumed dietary components) must have an acceptable flavor profile to promote intake. OBJECTIVE: The aim of this research was to model the influence of using herbs/spices as flavor-enhancers when reducing overconsumed dietary components in commonly consumed foods and evaluate acceptance of these flavor-enhanced reformulations. DESIGN: Ten leading sources of overconsumed dietary components were identified using the National Health and Nutrition Examination Survey 2015-2018 dietary data. These foods were reformulated to reduce overconsumed dietary components and herbs/spices were used to preserve acceptability. The influence of consumer adoption of the reformulated foods on intake of overconsumed dietary components was modeled using National Health and Nutrition Examination Survey data. Consumer acceptability of the reformulated recipes was assessed with blind taste testing. PARTICIPANTS/SETTING: Dietary data from adults aged 19 years and older (n = 9,812) included in the National Health and Nutrition Examination Survey 2015-2018 were used to identify foods for reformulation and model the potential influence of reformulation. The blind taste testing included 85 to 107 consumers per panel. MAIN OUTCOME MEASURES: Estimated daily change in total intake of saturated fat, sodium, added sugars, and energy with intake of the reformulated foods instead of the original foods. Consumer ratings of overall liking of the reformulated recipes vs the original recipes were assessed using standard 9-point hedonic scales. STATISTICAL ANALYSES PERFORMED: Descriptive statistics with use of survey procedures were used to model the influence of reformulated food adoption. Mixed effect models were used for analysis of the blind tasting data. RESULTS: With intake of the reformulated foods, instead of the original versions, by 25% to 100% of current consumers, estimates suggest lowering of saturated fat (25% consumer adoption to 100% consumer adoption -2.9% to -11.4%, respectively), sodium (-3.2 to -11.5%, respectively), and added sugars (-0.5 to -2.7%, respectively) intake. The overall liking ratings for seven of the 10 reformulated foods were superior or at parity with the original foods. CONCLUSIONS: This proof-of-concept research suggests that using herbs/spices to create flavor-enhanced recipes lower in overconsumed dietary components has the potential to reduce intake and is acceptable to consumers.

Parental cardiovascular disease and cardiovascular disease risk factors in the offspring: The Diet, Cancer and Health cohorts.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) aggregates in families and offspring with parental CVD may have adverse risk factor levels long time before the potential onset of CVD. We compared risk factor levels in offspring of parents with atherosclerotic CVD (ASCVD) and parents with no ASCVD at different parental ages at onset. METHODS: The study included 5751 participants (median age: 50 years) of the Diet, Cancer and Health - Next Generations study. Measurements included blood pressure, body composition and lipid fractions. Information on parental ASCVD and age at disease onset was obtained through register linkage. Parental ASCVD was defined as myocardial infarction, ischemic stroke or peripheral artery disease occurring <70 years, prematurely (mothers: <65 years fathers: <55 years), divided into age categories or using a broader classification of CVD. Linear regression models using Generalized Estimating Equations were used for analysis. Analyses were adjusted for age, sex, education, smoking, alcohol intake, physical activity and some additionally for BMI. RESULTS: Offspring with parental ASCVD had a higher blood pressure, waist circumference, BMI, visceral adipose tissue, percentage of body fat and non-HDL cholesterol levels, but not other lipid levels, compared to offspring with no parental ASCVD (all p < 0.01). Overall, the same patterns were observed for parental ASCVD occurring prematurely and using a broader CVD classification. CONCLUSIONS: Offspring with parental ASCVD had a higher blood pressure, higher body composition measures and higher non-HDL cholesterol levels compared to offspring with no parental ASCVD. Findings were overall consistent across different classifications of parental ASCVD.

Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study.

BACKGROUND & AIMS: The effect of walnut-related modulation of gut microbiota composition on microbiota functionality is unknown. The aim was to characterize the effect of a walnut-enriched diet (WD), compared to a fatty acid-matched diet devoid of walnuts (WFMD) and a diet where oleic acid replaces alpha-linolenic acid (ORAD), on bacterial gene expression. METHODS: A 3-period, randomized, crossover, controlled-feeding study was conducted. Participants were provided a 2-week run-in standard western diet (SWD; 50% kcal carbohydrate, 16% protein, 34% fat, 12% SFA). Following the SWD in random sequence order, participants were provided the WD, WFMD, and ORAD (48% carbohydrate; 17% protein; fat 35%; 7% SFA). The WD contained 18% of energy from walnuts (57 g/d/2100 kcal). The WFMD and ORAD were devoid of walnuts; liquid non-tropical plant oils were included in these diets. Metatranscriptomic analyses were performed as an exploratory outcome. RESULTS: The analytical sample included 35 participants (40% female) with a mean ± SD age of 43 ± 10 y and BMI of 30.3 ± 4.9 kg/m2. The ⍺-diversity of taxa actively expressing genes, assessed by observed species (p = 0.27) and Pielou's Evenness (p = 0.09), did not differ among the diets. The ⍺-diversity of actively expressed genes was greater following the WD compared to the WFMD and ORAD as assessed by the observed genes and Pielou's Evenness metrics (p < 0.05). ß-Diversity of the actively expressed genes differed following the WD compared to the WFMD (p = 0.001) and ORAD (p = 0.001); ß-diversity did not differ between the WFMD and ORAD. Active composition analyses showed increased Gordonibacter (p < 0.001) activity following the WD vs. the ORAD. Greater expression of many genes was observed following the WD compared to the WFMD and ORAD. Following the WD, greater expression of metabolism-related genes encoding glycine amidinotransferase (GATM; K00613) and arginine deiminase (K01478) was observed compared to the WFMD. Greater expression of glycine amidinotransferase (GATM; K00613) by Gordonibacter was also observed following the WD vs. the WFMD and ORAD. CONCLUSION: Our results suggest walnut intake may increase endogenous production of homoarginine through gut microbiota-mediated upregulation of GATM, which is a novel mechanism by which walnuts may lower cardiovascular disease risk. However, given the exploratory nature replication is needed. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT02210767).

Diet-derived and diet-related endogenously produced palmitic acid: Effects on metabolic regulation and cardiovascular disease risk.

Palmitic acid is the predominant dietary saturated fatty acid (SFA) in the US diet. Plasma palmitic acid is derived from dietary fat and also endogenously from de novo lipogenesis (DNL) and lipolysis. DNL is affected by excess energy intake resulting in overweight and obesity, and the macronutrient profile of the diet. A low-fat diet (higher carbohydrate and/or protein) promotes palmitic acid synthesis in adipocytes and the liver. A high-fat diet is another source of palmitic acid that is taken up by adipose tissue, liver, heart and skeletal muscle via lipolytic mechanisms. Moreover, overweight/obesity and accompanying insulin resistance increase non-esterified fatty acid (NEFA) production. Palmitic acid may affect cardiovascular disease (CVD) risk via mechanisms beyond increasing low-density lipoprotein-cholesterol (LDL-C), notably synthesis of ceramides and possibly through branched fatty acid esters of hydroxy fatty acids (FAHFAs) from palmitic acid. Ceramides are positively associated with incident CVD, whereas the role of FAHFAs is uncertain. Given the new evidence about dietary regulation of palmitic acid metabolism there is interest in learning more about how diet modulates circulating palmitic acid concentrations and, hence, potentially CVD risk. This is important because of the heightened interest in low carbohydrate (carbohydrate controlled) and high carbohydrate (low-fat) diets coupled with the ongoing overweight/obesity epidemic, all of which can increase plasma palmitic acid levels by different mechanisms. Consequently, learning more about palmitic acid biochemistry, trafficking and how its metabolites affect CVD risk will inform future dietary guidance to further lower the burden of CVD.

The effect of cottonseed oil on lipids/lipoproteins: a systematic review and plasma cholesterol predictive equations estimations.

CONTEXT: Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils. OBJECTIVES: To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations. DATA SOURCES: A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population. DATA ANALYSES: The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic). RESULTS: In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ -7.7 mg/dL) and triglycerides (≈ -7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ -14.8 mg/dL), LDL-C (≈ -14.0 mg/dL), and non-high-density lipoprotein cholesterol (≈ -14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (-8.1 mg/dL) and LDL-C (-7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (-1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL. CONCLUSION: Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins.

Contribution of Circulating Host and Microbial Tryptophan Metabolites Toward Ah Receptor Activation.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that plays an integral role in homeostatic maintenance by regulating cellular functions such as cellular differentiation, metabolism, barrier function, and immune response. An important but poorly understood class of AHR activators are compounds derived from host and bacterial metabolism of tryptophan. The commensal bacteria of the gut microbiome are major producers of tryptophan metabolites known to activate the AHR, while the host also produces AHR activators through tryptophan metabolism. We used targeted mass spectrometry-based metabolite profiling to determine the presence and metabolic source of these metabolites in the sera of conventional mice, germ-free mice, and humans. Surprisingly, sera concentrations of many tryptophan metabolites are comparable between germ-free and conventional mice. Therefore, many major AHR-activating tryptophan metabolites in mouse sera are produced by the host, despite their presence in feces and mouse cecal contents. Here we present an investigation of AHR activation using a complex mixture of tryptophan metabolites to examine the biological relevance of circulating tryptophan metabolites. AHR activation is rarely studied in the context of a mixture at relevant concentrations, as we present here. The AHR activation potentials of individual and pooled metabolites were explored using cell-based assays, while ligand binding competition assays and ligand docking simulations were used to assess the detected metabolites as AHR agonists. The physiological and biomedical relevance of the identified metabolites was investigated in the context of a cell-based model for rheumatoid arthritis. We present data that reframe AHR biology to include the presence of a mixture of ubiquitous tryptophan metabolites, improving our understanding of homeostatic AHR activity and models of AHR-linked diseases.

Self-reported and measured anthropometric variables in association with cardiometabolic markers: A Danish cohort study.

General obesity is a recognized risk factor for various metabolically related diseases, including hypertension, dyslipidemia, and pre-diabetes. In epidemiological studies, anthropometric variables such as height and weight are often self-reported. However, misreporting of self-reported data may bias estimates of associations between anthropometry and health outcomes. Further, few validation studies have compared self-reported and measured waist circumference (WC). This study aimed to quantify the agreement between self-reported and measured height, weight, body mass index (BMI), WC, and waist-to-height ratio (WHtR), and to investigate associations of these anthropometric measures with cardiometabolic biomarkers. A total of 39,514 participants aged above 18 years were included into the Diet, Cancer, and Health-Next Generation Cohort in 2015-19. Self-reported and measured anthropometric variables, blood pressure, and cardiometabolic biomarkers (HbA1c, lipid profiles, C-reactive protein and creatinine) were collected by standard procedures. Pearson correlations (r) and Lin's concordance correlations were applied to evaluate misreporting. Misreporting by age, sex and smoking status was investigated in linear regression models. Multivariable regression models and Receiver Operating Characteristic analyses assessed associations of self-reported and measured anthropometry with cardiometabolic biomarkers. Self-reported height was overreported by 1.07 cm, and weight was underreported by 0.32 kg on average. Self-reported BMI and WC were 0.42 kg/m2 and 0.2 cm lower than measured, respectively. Self-reported and measured height, weight, BMI, WC and WtHR were strongly correlated (r = 0.98, 0.99, 0.98, 0.88, 0.86, respectively). Age, sex, smoking, and BMI contributed to misreporting of all anthropometric measures. Associations between self-reported or measured anthropometric measures and cardiometabolic biomarkers were similar in direction and strength. Concordance between self-reported and measured anthropometric measures, including WC, was very high. Self-reported anthropometric measures were reliable when estimating associations with cardiometabolic biomarkers.

Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association.

Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations for lifestyle therapies to manage dyslipidemia. This Clinical Perspective provides an update with a focus on nutrition interventions for the three most common dyslipidemias in adults: 1) low-density lipoprotein cholesterol (LDL-C) elevation; 2) triglyceride (TG) elevation, including severe hypertriglyceridemia with chylomicronemia; and 3) combined dyslipidemia, with elevations in both LDL-C and TG levels. Lowering LDL-C and non-high-density lipoprotein cholesterol are the primary objectives for reducing ASCVD risk. With severe TG elevation (≥500 mg/dL), the primary objective is to prevent pancreatitis and ASCVD risk reduction is secondary. Nutrition interventions that lower LDL-C levels include reducing cholesterol-raising fatty acids and dietary cholesterol, as well as increasing intakes of unsaturated fatty acids, plant proteins, viscous fibers, and reducing adiposity for patients with overweight or obesity. Selected dietary supplements may be employed as dietary adjuncts. Nutrition interventions for all patients with elevated TG levels include restricting intakes of alcohol, added sugars, and refined starches. Additional lifestyle factors that reduce TG levels are participating in daily physical activity and reducing adiposity in patients with overweight or obesity. For patients with severe hypertriglyceridemia, an individualized approach is essential. Nutrition interventions for addressing concurrent elevations in LDL-C and TG include a combination of the strategies described for lowering LDL-C and TG. A multidisciplinary approach is recommended to facilitate success in making and sustaining dietary changes and the assistance of a registered dietitian nutritionist is highly recommended.

Popular Dietary Patterns: Alignment With American Heart Association 2021 Dietary Guidance: A Scientific Statement From the American Heart Association.

The evolution of dietary guidelines from isolated nutrients to broader dietary pattern recommendations results from growing knowledge of the synergy between nutrients and their food sources as they influence health. Macronutrient and micronutrient needs can be met by consuming various dietary patterns, but guidance is often required to facilitate population-wide adherence to wise food choices to achieve a healthy dietary pattern. This is particularly true in this era with the proliferation of nutrition misinformation and misplaced emphasis. In 2021, the American Heart Association issued a scientific statement outlining key principles of a heart-healthy dietary pattern that could be operationalized in various ways. The objective of this scientific statement is to assess alignment of commonly practiced US dietary patterns with the recently published American Heart Association criteria, to determine clinical and cultural factors that affect long-term adherence, and to propose approaches for adoption of healthy dietary patterns. This scientific statement is intended to serve as a tool for clinicians and consumers to evaluate whether these popular dietary pattern(s) promote cardiometabolic health and suggests factors to consider when adopting any pattern to improve alignment with the 2021 American Heart Association Dietary Guidance. Numerous patterns strongly aligned with 2021 American Heart Association Dietary Guidance (ie, Mediterranean, DASH [Dietary Approaches to Stop Hypertension], pescetarian, vegetarian) can be adapted to reflect personal and cultural preferences and budgetary constraints. Thus, optimal cardiovascular health would be best supported by developing a food environment that supports adherence to these patterns wherever food is prepared or consumed.

Dried Fruits: Bioactives, Effects on Gut Microbiota, and Possible Health Benefits-An Update.

Dried fruits contain many bioactive compounds broadly classified as phytochemicals including phenolics, flavonoids, carotenoids, proanthocyanidins, stilbenes, chalcones/dihydrochalcones, and phytoestrogens. These compounds have antioxidant effects that may benefit health. Dried fruits are also a diverse group of foods with varying fibre contents. The evaluation of the biological activity of these bioactive compounds, including their bioaccessibility and bioavailability, may contribute to the understanding of the health effects of dried fruits. Limited evidence suggests that dried fruits (raisins, cranberries, dates, and prunes) affect human gut microbiota composition in a potentially beneficial manner (in terms of effects on Bifidobacteria, Faecalibacterium prausnitzii, Lactobacillus, Ruminococcaceae, Klebsiella spp., and Prevotella spp.). There is little epidemiological evidence about the association of dried fruit consumption with cardiovascular disease incidence and mortality, as well as the risk of type 2 diabetes or obesity. Clinical trial evidence for the effects of dried fruit consumption on cardiovascular risk factors, including glycaemic control, is mixed. Clinical trial evidence suggests prunes might preserve bone mineral density in postmenopausal women. Consumption of dried fruits is associated with higher-quality diets. Studies are needed to increase our understanding of the health effects of dried fruits and the underlying biological mechanisms.