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Understanding nutrient intake of anorexia nervosa (AN) patients is essential for the treatment. Therefore, estimates of total energy and nutrient consumption were made in a group of young women (19 to 30 years) with restricting and binge purge subtypes of

Objective: To determine if human Zn absorption adapts to chronic high Zn intakes.Methods: Zn absorption was measured at 0, 8, and 16 wk in healthy postmenopausal women who consumed controlled diets with approximately 5 mg Zn from food, supplemented to 14 (n = 6), 32 (n = 3), or 47 (n = 3) mg Zn/d for 22 wk. Zn absorption for 1 day was determined by (65)Zn-labeling of meals and whole body scintillation counting.Results: At wk 0, less Zn was absorbed from diets with 14, compared with 32 or 47 mg/d (4.6, 8.7, and 10.3 mg/d, respectively; pooled SE = 0.9; p < 0.05). These differences were not apparent at wk 8 (5.4, 5.8, 6.4; NS) and became negligible by wk 16 (5.0, 5.0, 5.1; NS). Plasma Zn concentrations were unaffected. The results are consistent with a saturation response model of Zn absorption.Conclusion: Within several weeks, postmenopausal women biologically adapted to absorb a relatively uniform amount of 5 mg Zn/d when controlled, Zn-supplemented diets supplied consistent Zn intakes between 14 and 47 mg/d. [ABSTRACT FROM AUTHOR]

Testicular epidermoid cysts are benign tumors that represent only 1% of all testicular tumors. This tumor presents as a palpable mass within the testicle. High-resolution sonography can help provide a presurgical diagnosis due to the tumor's unique sonographic appearance of a 'bow tie' echogenicity. This bow tie pattern is formed by the deposition of keratin in layers by the lining of the cyst. A preoperative sonographic diagnosis of a testicular epidermoid cyst can lead to testicle-sparing surgery in healthy, young males due to the benign nature of this tumor. [ABSTRACT FROM AUTHOR]

The Breastfeeding Attrition Prediction Tool (BAPT) is based on the theory of planned behavior, which explains behavior as a function of attitudes, subjective norm, and perceived control. The BAPT subscales are positive and negative attitudes toward breastfeeding, family and professional expectations, and perceived ability to be successful. The purpose of this study was to test the reliability and validity of the BAPT among 269 women who planned to breastfeed for at least 8 weeks. Subjects completed the BAPT in the hospital and during a telephone interview at 8 weeks. Based on factor analysis, several items were deleted. Using discriminant function analysis, the modified BAPT was an effective predictor of 78% of women who stopped breastfeeding before 8 weeks and 68% of those who were still breastfeeding. There is potential for the modified BAPT to be an adjunct for the clinician in identifying women at risk for early cessation of breastfeeding. [ABSTRACT FROM AUTHOR]

Cutaneous wounds close more slowly in rats and monkeys as age increases. Caloric restriction of 40% in rats and 30% in monkeys did not significantly affect healing rates, although it did exert a trend toward faster closure. Similarly, voluntary exercise did not significantly alter healing rates in rats. Thus, impaired wound healing appears to be a generalized physiological manifestation of aging, but its possible amelioration by "anti-aging" interventions remains to be established. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are becoming the standard of care for recurrent and metastatic cancer. Opioids, the primary treatment for cancer-related pain, are immunosuppressive raising concerns about their potential to interfere with the efficacy of ICIs. We hypothesize that exogenous opioids given for analgesia suppress antitumor immunity via T cell-mediated mu opioid receptor 1 (OPRM1) signaling., Methods: In silico bioinformatics were used to assess OPRM1 receptor expression on tumor-infiltrating immune cells in patients with head and neck squamous cell carcinoma (HNSCC) and across different cancer types. A syngeneic orthotopic mouse model of oral squamous cell carcinoma was used to study the impact of morphine and OPRM1 antagonism on tumor-infiltrating immune cells, tumor growth and antitumor efficacy of anti-Programmed cell death protein 1 (PD-1) monoclonal antibody treatment., Results: In patients with HNSCC, OPRM1 expression was most abundant in CD8+ T cells, particularly in patients who had not been prescribed opioids prior to resection and exhibited increased expression of exhaustion markers. Exogenous morphine treatment in tumor-bearing mice reduced CD4+ and CD8+ T-cell infiltration and subsequently anti-PD1 ICI efficacy. Peripherally acting mu opioid receptor antagonism, when administered in the adjunctive setting, was able to block morphine-induced immunosuppression and recover the antitumor efficacy of anti-PD1., Conclusions: These findings suggest that morphine acts via a peripheral OPRM1-mediated mechanism to suppress CD8+ T cells, thereby fostering a pro-tumor-impaired immune response. Importantly, peripherally-restricted OPRM1 antagonism can effectively block this morphine-induced immunosuppression while still allowing for centrally-mediated analgesia, indicating a potential therapeutic strategy for mitigating the adverse effects of opioid pain relief in cancer treatment., Competing Interests: Competing interests: DNT and LKJ are Employees and Shareholders of Glycyx MOR, Inc. and supplied the mu opioid antagonist, axelopran. They did not provide any funding for the study. DPZ declares competing interests with BICARA (steering committee), Seagen (steering committee), Inhibrx (consulting), Macrogenics (consulting), Prelude Therapeutics (advisory board), and Merck (advisory board) and research support (institutional) from clinical trials with Merck, BMS, AstraZeneca, GlaxoSmithKline, Aduro, Macrogenics, Bicara, and Novasenta. RLF reports grants or contracts from AstraZeneca/MedImmune, Bristol Myers Squibb, Merck, Novasenta, Tesaro; consulting fees with Adagene, Aduro Biotech, Bicara Therapeutics, Brooklyn ImmunoTherapeutics, Catenion, EMD Serono, Everest Clinical Research Corporation, F. Hoffman-La Roche Ltd., Federation Bio, Genocea Biosciences, Kowa Research Institute, Mirati Therapeutics, Nanobiotix, Novartis, Novasenta, PPD Development, Sanofi, Zymeworks; participation on a data safety monitoring or advisory board with Coherus BioSciences, Eisai Europe Ltd., Genmab, Hookipa, Instil Bio, Lifescience Dynamics, MacroGenics, MeiraGtx, Merck, Mirror Biologics, Numab Therapeutics AG, OncoCyte, Pfizer, Rakuten Medical, Seagen, SIRPant Immunotherapeutics, Vir Biotechnology, stock or stock options with Novasenta., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Restricted carbohydrate diets remain among the most popular for weight loss and general health improvement. Recent evidence demonstrates that carbohydrate restricted diets are low in overall diet quality, yet their association with micronutrient inadequacy has not been well characterized at a population-level in adults in the United States., Objective: 1) To evaluate the prevalence of not meeting daily micronutrient recommendations in US adults that met the Acceptable Macronutrient Distribution Ranges (AMDRs) and those who restricted carbohydrate to <45% energy, and 2) examine the effect of total fat and fat class on these results for the restricted carbohydrate group., Design: This study utilized 24-hour recall data on food and nutrient intake from respondents in the National Health and Nutrition Examination Survey (NHANES) 2007-2018., Participants/setting: This study included 15,029 respondents who were ≥20 y, had complete and reliable nutrient intake data, and were not pregnant or breastfeeding., Main Outcome Measures: The main outcome was the prevalence of not meeting daily micronutrient recommendations based on Dietary Reference Intakes (DRIs)., Statistical Analyses Performed: The National Cancer Institute's usual intake methodology was used to estimate usual dietary intake and the prevalence of the US adult population not meeting the DRIs., Results: Compared to participants that met the AMDRs, those that consumed restricted carbohydrate diets had greater prevalence of inadequacy (%

Reducing the environmental pressures stemming from food production is central to meeting global sustainability targets. Shifting diets represents one lever for improving food system sustainability, and identifying sustainable diet opportunities requires computational models to represent complex systems and allow users to evaluate counterfactual scenarios. Despite an increase in the number of food system sustainability models, there remains a lack of transparency of data inputs and mathematical formulas to facilitate replication by researchers and application by diverse stakeholders. Further, many models lack the ability to model multiple geographic scales. The present study introduces Foodprint 2.0, which fills both gaps. Foodprint 2.0 is an updated biophysical simulation model that estimates the agricultural resource requirements of diet patterns and can be adapted to suit a variety of research purposes. The objectives of this study are to: 1) describe the new features of Foodprint 2.0, and 2) demonstrate model performance by estimating the agricultural resource requirements of food demand in the United States (US) using nationally representative dietary data from the National Health and Nutrition Examination Survey from 2009-2018. New features of the model include embedded functions to integrate individual-level dietary data that allow for variance estimation; new data and calculations to account for the resource requirements of food trade and farmed aquatic food; updated user interface; expanded output data for over 200 foods that include the use of fertilizer nutrients, pesticides, and irrigation water; supplementary files that include input data for all parameters on an annual basis from 1999-2018; sample programming code; and step-by-step instructions for users. This study demonstrates that animal-sourced foods consumed in the US accounted for the greatest share of total land use, fertilizer nutrient use, pesticide use, and irrigation water use, followed by grains, fruits, and vegetables. Greater adherence to the Dietary Guidelines for Americans was associated with lower use of land and fertilizer nutrients, and greater use of pesticides and irrigation water. Foodprint 2.0 is a highly modifiable model that can be a useful resource for informing sustainable diet policy discussions., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ZC has research awards from the US Department of Agriculture and The Thomas F. and Kate Miller Jeffress Memorial Trust, and received honoraria from the National Dairy Council for professional activities unrelated to the present research. ER has research awards from the US Department of Agriculture and the Foundation for Food & Agriculture Research for projects unrelated to the present study. DCL was supported by the Johns Hopkins Center for a Livable Future with a gift from the Greater Kansas City Community Foundation. NB receives funding from the Robert Wood Johnson Foundation as a Health Policy Research Scholar., (Copyright: © 2024 Conrad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Roux-en-Y gastric bypass (RYGB) is associated with reduced cardiovascular (CV) risk factors, morbidity, and mortality. Whether these effects are specifically induced by the surgical procedure or the weight loss is unclear., Objective: To compare 6-week changes in CV risk factors in patients with obesity undergoing matching caloric restriction and weight loss by RYGB or a very low-energy diet (VLED)., Design, Setting, and Participants: This nonrandomized controlled study (Impact of Body Weight, Low Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers [COCKTAIL]) was conducted at a tertiary care obesity center in Norway. Participants were individuals with severe obesity preparing for RYGB or a VLED. Recruitment began February 26, 2015; the first patient visit was on March 18, 2015, and the last patient visit (9-week follow-up) was on August 9, 2017. Data were analyzed from April 30, 2021, through June 29, 2023., Interventions: VLED alone for 6 weeks or VLED for 6 weeks after RYGB; both interventions were preceded by 3-week LED., Main Outcomes and Measures: Between-group comparisons of 6-week changes in CV risk factors., Results: Among 78 patients included in the analyses, the mean (SD) age was 47.5 (9.7) years; 51 (65%) were women, and 27 (35%) were men. Except for a slightly higher mean (SD) body mass index of 44.5 (6.2) in the RYGB group (n = 41) vs 41.9 (5.4) in the VLED group (n = 37), baseline demographic and clinical characteristics were similar between groups. Major atherogenic blood lipids (low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein[a]) were reduced after RYGB in comparison with VLED despite a similar fat mass loss. Mean between-group differences were -17.7 mg/dL (95% CI, -27.9 to -7.5), -17.4 mg/dL (95% CI, -29.8 to -5.0) mg/dL, -9.94 mg/dL (95% CI, -15.75 to -4.14), and geometric mean ratio was 0.55 U/L (95% CI, 0.42 to 0.72), respectively. Changes in glycemic control and blood pressure were similar between groups., Conclusions and Relevance: This study found that clinically meaningful reductions in major atherogenic blood lipids were demonstrated after RYGB, indicating that RYGB may reduce CV risk independent of weight loss., Trial Registration: ClinicalTrials.gov Identifier: NCT02386917.

This article summarizes the lessons learned from the COCKTAIL study: an open, three-armed, single-center study including patients with obesity scheduled for treatment with Roux-en-Y gastric bypass (RYGB) or nonsurgical calorie restriction, and a normal- to overweight control group. The clinical implications of the results from multiple peer-reviewed articles describing the effects of RYGB, severe caloric restriction, weight loss, and type 2 diabetes on the in vivo activity and protein expression of drug-metabolizing enzymes (cytochrome P450 (CYP) 1A2, 2C9, 2C19, and 3A) and transporters (DMETs; organic anion-transporting polypeptide (OATP) 1B1 and P-glycoprotein (P-gp)) are discussed in the perspective of three clinically relevant questions: (1) How should clinicians get the dose right in patients after RYGB? (2) Will drug disposition in patients with obesity be normalized after successful weight loss? (3) Are dose adjustments needed according to obesity and diabetes status? Overall, RYGB seems to have a lower impact on drug disposition than previously assumed, but clinicians should pay close attention to drugs with a narrow therapeutic range or where a high maximum drug concentration may be problematic. Whether obesity-related alterations of DMETs normalize with substantial weight loss depends on the DMET in question. Obesity and diabetes downregulate the in vivo activity of CYP2C19 and CYP3A (only obesity) but whether substrate drugs should be dose adjusted is also dependent on other factors that influence clearance, that is, liver blood flow and protein binding. Finally, we recommend frequent and individualized follow-up due to high inter- and intraindividual variability in these patients, particularly following RYGB., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

We investigated the putative redundancy of the Dark Tetrad (specifically, Machiavellianism-psychopathy and sadism-psychopathy) through an examination of the differences between correlations with self-reported narrowband personality traits. In addition to measures of the Dark Tetrad, participants in four studies completed measures of various narrowband traits assessing general personality, aggression, impulsivity, Mimicry Deception Theory, and Reinforcement Sensitivity Theory. Results generally supported empirical distinctions between Machiavellianism and psychopathy, and between sadism and psychopathy. Machiavellianism significantly differed from psychopathy across correlations for nine of 10 traits (Study 1), 8 of 25 facets (Study 2), aggression (Study 3), 12 of 25 facets (Study 3), four of five facets (Study 4), impulsivity (Study 4), and five of six facets (Study 4). Sadism significantly differed from psychopathy across correlations with five of 10 traits (Study 1), eight of 25 facets (Study 2), reactive aggression (Study 3), 10 of 25 facets (Study 3), three of six facets (Study 4), impulsivity (Study 4), and three of six facets (Study 4). Our findings challenge the claims that Machiavellianism and psychopathy, as well as sadism and psychopathy, as currently measured, are redundant., (© 2024. The Author(s).)

Background: Mischaracterization of dietary intake by patients and study participants is a common problem that presents challenges to clinical and public health approaches to improve diet quality, identify healthy eating patterns, and reduce the risk of chronic disease., Objective: This study examined participants' self-reported adherence to low-carbohydrate and low-fat diets compared with their estimated adherence using up to 2 24-hour recalls., Design: This cross-sectional study acquired data on dietary intake from respondents in the National Health and Nutrition Examination Survey, 2007-2018., Participants/setting: This study included 30 219 respondents aged 20 years and older who had complete and reliable dietary data and were not pregnant or breastfeeding., Main Outcome Measures: The main outcome was prevalence of self-reported and estimated adherence to low-carbohydrate or low-fat diet patterns., Statistical Analyses Performed: Self-reported adherence to low-carbohydrate or low-fat diets was evaluated using responses to questionnaires. Estimated adherence to these diets was assessed using data from up to 2 24-hour recalls and usual intake methodology developed by the National Cancer Institute., Results: Of the 1.4% of participants who reported following a low-carbohydrate diet, estimated adherence (<26% energy from carbohydrates) using 24-hour recalls was 4.1%, whereas estimated adherence among those that did not report following a low-carbohydrate diet was <1% (P value for difference = .014). Of the 2.0% of participants who reported following a low-fat diet, estimated adherence (<30% energy from fat) was 23.0%, whereas estimated adherence among those who did not report following a low-fat diet was 17.8% (P value for difference = .048)., Conclusions: This research demonstrates that most individuals mischaracterized their diet pattern when compared with up to 2 24-hour recalls. These findings emphasize the need for clinicians and public health professionals to be cautious when interpreting individuals' self-reported diet patterns, and should aim to collect more detailed dietary data when possible., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Selective inhibition of the RGD (Arg-Gly-Asp) integrin αvβ1 has been recently identified as an attractive therapeutic approach for the treatment of liver fibrosis given its function, target expression, and safety profile. Our identification of a non-RGD small molecule lead followed by focused, systematic changes to the core structure utilizing a crystal structure, in silico modeling, and a tractable synthetic approach resulted in the identification of a potent small molecule exhibiting a remarkable affinity for αvβ1 relative to several other integrin isoforms measured. Azabenzimidazolone 25 demonstrated antifibrotic efficacy in an in vivo rat liver fibrosis model and represents a tool compound capable of further exploring the biological consequences of selective αvβ1 inhibition.

Introduction: Cardiometabolic diseases (CMD) are the leading causes of death for people living in the United States. Dietary strategies, such as restricting carbohydrate intake, are becoming popular strategies for improving health status. However, there is limited and often contradictory evidence on whether restricting carbohydrate intake is related to all-cause, CMD, or cardiovascular disease (CVD) mortality., Methods: The objective of the present study was to evaluate the association between restricted carbohydrate diets (<45%en) and mortality from all-causes, CMD, and CVD, stratified by fat amount and class. Data were acquired using the National Health and Nutrition Examination Survey (1999-2018) linked with mortality follow-up until December 31, 2019 from the Public-use Linked Mortality Files. Multivariable survey-weighted Cox proportional hazards models estimated hazard ratios for 7,958 adults (≥20 y) that consumed <45%en from carbohydrates and 27,930 adults that consumed 45-65%en from carbohydrates., Results: During the study period a total of 3,780 deaths occurred, including 1,048 from CMD and 1,007 from CVD, during a mean follow-up of 10.2 y. Compared to individuals that met carbohydrate recommendations (45-65%en), those that consumed carbohydrate restricted diets (<45%en) did not have significantly altered risk of mortality from all-causes (HR: 0.98; 95% CI: 0.87, 1.11), CMD (1.18; 0.95, 1.46), or CVD (1.20; 0.96, 1.49). These findings were maintained when the restricted carbohydrate diet group was stratified by intake of total fat, saturated fat (SFA), monounsaturated fat (MUFA), and polyunsaturated fat (PUFA)., Discussion: Carbohydrate restriction (<45%en) was not associated with mortality from all-causes, CVD, or CMD. Greater efforts are needed to characterize the risk of mortality associated with varied degrees of carbohydrate restriction, e.g., low (<26%en) and high (>65%en) carbohydrate diets separately., Competing Interests: ZC has research awards from The Thomas F. and Kate Miller Jeffress Memorial Trust for a project unrelated to the present study; and received honoraria from MKYoung Food & Nutrition Strategies, National Geographic Society, The Ohio State University, Routledge, Princeton University Press, and Nutrition Today for professional activities unrelated to the present research. MB has a research award from the United Soybean Board that has no relevance to the present project. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Angelotti, Kowalski, Johnson, Belury and Conrad.)

Background and Objective: Several drugs on the market are substrates for P-glycoprotein (P-gp), an efflux transporter highly expressed in barrier tissues such as the intestine. Body weight, weight loss, and a Roux-en-Y gastric bypass (RYGB) may influence P-gp expression and activity, leading to variability in the drug response. The objective of this study was therefore to investigate digoxin pharmacokinetics as a measure of the P-gp phenotype in patients with obesity before and after weight loss induced by an RYGB or a strict diet and in normal weight individuals., Methods: This study included patients with severe obesity preparing for an RYGB (n = 40) or diet-induced weight loss (n = 40) and mainly normal weight individuals scheduled for a cholecystectomy (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day) followed by an additional 6 weeks of <800 kcal/day induced by an RYGB (performed at week 3) or a very-low-energy diet. Follow-up time was 2 years, with four digoxin pharmacokinetic investigations at weeks 0, 3, and 9, and year 2. Hepatic and jejunal P-gp levels were determined in biopsies obtained from the patients undergoing surgery., Results: The RYGB group and the diet group had a comparable weight loss in the first 9 weeks (13 ± 2.3% and 11 ± 3.6%, respectively). During this period, we observed a minor increase (16%) in the digoxin area under the concentration-time curve from zero to infinity in both groups: RYGB: 2.7 µg h/L [95% confidence interval (CI) 0.67, 4.7], diet: 2.5 µg h/L [95% CI 0.49, 4.4]. In the RYGB group, we also observed that the time to reach maximum concentration decreased after surgery: from 1.0 ± 0.33 hours at week 3 to 0.77 ± 0.08 hours at week 9 (-0.26 hours [95% CI -0.47, -0.05]), corresponding to a 25% reduction. Area under the concentration-time curve from zero to infinity did not change long term (week 0 to year 2) in either the RYGB (1.1 µg h/L [-0.94, 3.2]) or the diet group (0.94 µg h/L [-1.2, 3.0]), despite a considerable difference in weight loss from baseline (RYGB: 30 ± 7%, diet: 3 ± 6%). At baseline, the area under the concentration-time curve from zero to infinity was -5.5 µg h/L [95% CI -8.5, -2.5] (-26%) lower in patients with obesity (RYGB plus diet) than in normal weight individuals scheduled for a cholecystectomy. Further, patients undergoing an RYGB had a 0.05 fmol/µg [95% CI 0.00, 0.10] (29%) higher hepatic P-gp level than the normal weight individuals., Conclusions: Changes in digoxin pharmacokinetics following weight loss induced by a pre-operative low-energy diet and an RYGB or a strict diet (a low-energy diet plus a very-low-energy diet) were minor and unlikely to be clinically relevant. The lower systemic exposure of digoxin in patients with obesity suggests that these patients may have increased biliary excretion of digoxin possibly owing to a higher expression of P-gp in the liver., (© 2023. The Author(s).)

Introduction: Fifty-two percent of adults in the United States reported following a popular diet pattern in 2022, yet there is limited information on daily micronutrient intakes associated with these diet patterns. The objective of the present study was to model the impact on micronutrient intake when foods highest in added sugar and sodium were replaced with healthier alternatives to align with the Dietary Guidelines for Americans recommendations., Methods: Dietary data were acquired from 34,411 adults ≥ 20 y in the National Health and Nutrition Examination Survey, 2005-2018. The National Cancer Institute methodology was used to estimate usual dietary intake at baseline of 17 micronutrients using information from up to two dietary recalls per person. A food substitution model was used to evaluate the impact on micronutrient intake when three servings of foods highest in added sugar and sodium were substituted with healthier alternatives., Results: Dietary modeling to replace foods highest in added sugar with healthier alternatives increased the mean intake of fat-soluble vitamins (0.15% for vitamin A to 4.28% for vitamin K), most water-soluble vitamins (0.01% for vitamin B 1 to 12.09% for vitamin C), and most minerals (0.01% for sodium to 4.44% for potassium) across all diet patterns. Replacing foods highest in sodium had mixed effects on the mean intake of micronutrients. The intake of most fatsoluble vitamins increased by 1.37-6.53% (particularly vitamin A and D), yet while the intake of some water-soluble vitamins and minerals increased by 0.18-2.64% (particularly vitamin B 2 , calcium, and iron) others decreased by 0.56-10.38% (notably vitamin B 3 and B 6 , magnesium, sodium, and potassium)., Discussion: Modeled replacement of foods highest in added sugar led to more favorable changes in mean micronutrient intake compared to modeled replacement of foods highest in sodium. Due to the composite nature of mixed dishes that include multiple ingredients, food substitutions may result in both favorable and unfavorable changes in micronutrient intake. These findings highlight the challenges of making singleitem food substitutions to increase micronutrient intake and call for further research to evaluate optimal combinations of replacement foods to maximize the intake of all micronutrients simultaneously., Competing Interests: ZC: had research awards from the Thomas F. and Kate Miller Jeffress Memorial Trust for a project unrelated to the present study; and received honoraria from Routledge, Princeton University Press, MKYoung Food & Nutrition Strategies, National Geographic Society, The Ohio State University, and Nutrition Today for professional activities unrelated to the present research. MB: had a research award from the United Soybean Board that has no relevance to the present project and serves on the Board of Directors for the American Society for Nutrition in a role that is unrelated to this project. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Basak Tukun, Rowe, Johnson, Love, Belury and Conrad.)

Background: More than one-third of adults in the United States have metabolic syndrome, and dietary carbohydrate intake may modify the likelihood of developing this condition. Currently, there is a lack of consistent evidence demonstrating the relationship between carbohydrate intake that falls below recommendations and metabolic syndrome. Not accounting for the differences in fatty acid classes of these dietary patterns may be a reason for inconsistent findings., Objective: This study evaluated the association between a carbohydrate intake below recommendations and metabolic syndrome stratified by fat quantity and fatty acid classes in a nationally representative sample of US adults., Design: This cross-sectional study acquired data on food and nutrient intake and markers of metabolic syndrome from respondents in the National Health and Nutrition Examination Survey 1999-2018., Participants/setting: This study included 19,078 respondents who were aged 20 years or older, had reliable and complete data on food and nutrient intake and markers of metabolic syndrome, and were not pregnant or breastfeeding., Main Outcome Measures: The main outcome was prevalence of metabolic syndrome., Statistical Analyses Performed: Usual dietary intake was estimated using the National Cancer Institute's usual intake methodology. Multivariable logistic regression models assessed the relative odds of prevalent metabolic syndrome between those who had a carbohydrate intake below recommendations and those who met carbohydrate recommendations., Results: Those who had a carbohydrate intake below recommendations had 1.067 (95% CI 1.063 to 1.071) times greater odds of having metabolic syndrome compared with those who met carbohydrate recommendations (P < 0.001). High intake of fat of any class was associated with higher odds of metabolic syndrome (total fat: 1.271, 95% CI 1.256 to 1.286; saturated fatty acid: 1.072, 95% CI 1.060 to 1.085; monounsaturated fatty acid: 1.317, 95% CI 1.300 to 1.333; polyunsaturated fatty acid: 1.056, 95% CI 1.047 to 1.066; P < 0.001 for all comparisons) in those who had a carbohydrate intake below recommendations., Conclusions: The odds of prevalent metabolic syndrome were higher among individuals who had a carbohydrate intake below recommendations compared with individuals who met carbohydrate recommendations., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Bariatric surgery is the most effective treatment for obesity but is invasive and associated with serious complications. Endoscopic sleeve gastroplasty (ESG) is a less invasive weight loss procedure to reduce the stomach volume by full-thickness sutures. ESG has been adopted in many countries, but implementation at Scandinavian centres has not yet been documented. We performed a clinical pilot trial at a Norwegian centre with the primary objective to assess the feasibility of the ESG procedure., Patients and Methods: We included the first 10 patients treated with ESG at a Norwegian centre in a single-arm pilot study. The eligibility criteria were either a body mass index (BMI) of 40-49.9 kg/m 2 , BMI 35-39.9 kg/m 2 and at least one obesity-related comorbidity, or BMI 30-34.9 kg/m 2 and type 2 diabetes. Patient follow-up resembled the scheme used for bariatric surgery at the center, including dietary plans and outpatient visits., Results: All procedures were technically successful except for one patient who had adhesions between the stomach and anterior abdominal wall, related to a prior hernia repair, resulting in less-than-intended stomach volume reduction. Mean total body weight loss (TBWL) after 26 and 52 weeks was 12.2% (95% CI 8.1-16.2) and 9.1% (95% CI 3.3 - 15.0). One patient experienced a minor suture-induced diaphragmatic injury, which was successfully managed conservatively., Conclusions: This first Scandinavian clinical trial of ESG, documenting the implementation of the procedure at a Norwegian center, demonstrated acceptable feasibility and safety, with large variations in individual weight loss during the 52-week follow-up period.

A radical/polar crossover annulation between allyl-substituted arenes and electron-deficient alkenes is described. Cobalt-catalyzed hydrogen atom transfer (HAT) facilitates tandem radical C-C bond formation that generates functionalized tetralin products in the face of potentially problematic hydrofluorination, hydroalkoxylation, hydrogenation, alkene isomerization, and radical polymerization reactions. The reactions proceed under mild conditions that tolerate many functional groups, leading to a broad substrate scope. This powerful ring-forming reaction very quickly assembles complex tetralins that are the formal products of the largely infeasible Diels-Alder cycloadditions of styrenes., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Introduction: Rosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity., Methods: Patients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; < 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; < 800 kcal/day)., Results: A total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant., Conclusions: Neither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance., (© 2023. The Author(s).)

Background: The randomized Oseberg study compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the 1-y remission of type 2 diabetes and β-cell function (primary outcomes). However, little is known about the comparable effects of SG and RYGB on the changes in dietary intakes, eating behavior, and gastrointestinal discomfort., Objectives: To compare 1-y changes in intakes of macro- and micronutrients, food groups, food tolerance, hedonic hunger, binge eating, and gastrointestinal symptoms after SG and RYGB., Methods: Among others, prespecified secondary outcomes were dietary intake, food tolerance, hedonic hunger, binge eating, and gastrointestinal symptoms assessed with a food frequency questionnaire, food tolerance questionnaire, Power of food scale, Binge eating scale, and Gastrointestinal symptom rating scale, respectively., Results: A total of 109 patients (66% females), with mean (SD) age 47.7 (9.6) y and body mass index of 42.3 (5.3) kg/m 2 , were allocated to SG (n = 55) or RYGB (n = 54). The SG group had, compared with the RYGB group, greater 1-y reductions in the intakes of: protein, mean (95% CI) between-group difference, -13 (-24.9, -1.2) g; fiber, -4.9 (-8.2, -1.6) g; magnesium, -77 (-147, -6) mg; potassium, -640 (-1237, -44) mg; and fruits and berries, -65 (-109, -20) g. Further, the intake of yogurt and fermented milk products increased by >2-folds after RYGB but remained unchanged after SG. In addition, hedonic hunger and binge eating problems declined similarly after both surgeries, whereas most gastrointestinal symptoms and food tolerance remained stable at 1 y., Conclusions: The 1-y changes in dietary intakes of fiber and protein after both surgical procedures, but particularly after SG, were unfavorable with regard to current dietary guidelines. For clinical practice, our findings suggest that health care providers and patients should focus on sufficient intakes of protein, fiber, and vitamin and mineral supplementation after both SG and RYGB. This trial was registered at [clinicaltrials.gov] as [NCT01778738]., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Childhood obesity is associated with adult obesity, which is a risk factor for chronic diseases. Obesity, as an environmental cue, alters circadian rhythms. The hypothesis of this study was that consumption of a high-fat diet alters metabolic rhythms in pubertal mice., Methods: Weanling female C57BL/6NHsd mice were fed a standard AIN93G diet or a high-fat diet (HFD) for 3 weeks. Livers were collected from six-week-old mice every 4 h over a period of 48 h for transcriptome analysis., Results and Discussion: The HFD altered rhythmicity of differentially rhythmic transcripts in liver. Specifically, the HFD elevated expression of circadian genes Clock , Per1 , and Cry1 and genes encoding lipid metabolism Fads1 and Fads2 , while decreased expression of circadian genes Bmal1 and Per2 and lipid metabolism genes Acaca , Fasn , and Scd1 . Hierarchical clustering analysis of differential expression genes showed that the HFD-mediated metabolic disturbance was most active in the dark phase, ranging from Zeitgeber time 16 to 20. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes showed that the HFD up-regulated signaling pathways related to fatty acid and lipid metabolism, steroid and steroid hormone biosynthesis, amino acid metabolism and protein processing in the endoplasmic reticulum, glutathione metabolism, and ascorbate and aldarate metabolism in the dark phase. Down-regulations included MAPK pathway, lipolysis in adipocytes, Ras and Rap1 pathways, and pathways related to focal adhesion, cell adhesion molecules, and extracellular matrix-receptor interaction. In summary, the HFD altered metabolic rhythms in pubertal mice with the greatest alterations in the dark phase. These alterations may disrupt metabolic homeostasis in puberty and lead to metabolic disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Sundaram, Rust, Palmer, Johnson and Zeng.)

Background: Cardiometabolic diseases (CMDs), which include heart disease, stroke, and diabetes, account for over one-third of the mortality burden in the United States annually. Nearly one-half of all deaths from CMD are attributable to suboptimal diet quality, and many Americans are turning to special diets for general health improvement. Among the most popular of these diets restrict daily carbohydrate intake to <45% of energy, yet their association with CMD is not well understood., Objectives: This study evaluated the association between restricted carbohydrate diets and prevalent CMD, stratified by fat intake., Methods: Dietary and CMD data were retrieved from 19,078 participants aged ≥20 y in the National Health and Nutrition Examination Survey, 1999-2018. The National Cancer Institute methodology was used to assess usual dietary intake., Results: Compared to participants that met recommendations for all macronutrients, those that consumed restricted carbohydrate diets were 1.15 (95% CI: 1.14, 1.16) times as likely to have CMD; and those that met recommendations for carbohydrates, but not all macronutrients, were 1.02 (95% CI: 1.02, 1.03) times as likely to have CMD. Higher intakes of saturated and polyunsaturated fat were associated with greater prevalence of CMD in restricted and recommended carbohydrate intake groups. Higher intake of monounsaturated fat was associated with lower prevalence of CMD among participants that met carbohydrate, but not all macronutrient, recommendations., Conclusions: To our knowledge, this is the first nationally representative study to evaluate the relationship between carbohydrate restriction and CMD, stratifying by fat intake. Greater efforts are needed to understand longitudinal relationships between carbohydrate restriction and CMD., (© 2023 The Authors.)

Adults in the United States are increasingly following 'popular' diet patterns that restrict food groups, macronutrients, or eating time. However, the intake of food groups associated with these diet patterns has not been well characterized. The objectives of this study were to (1) characterize the mean intake of food groups among consumers of popular diet patterns in the US, and (2) model the effect of targeted food substitutions on the intake of food groups. Data were acquired from the National Health and Nutrition Examination Survey, 2005-2018 (n = 34,411). A diet model was developed to assess the effects of replacing one serving each of foods highest in added sugar, sodium, saturated fat, and refined grains with healthy alternatives on the intake of key food groups for each diet pattern. Modeled replacement resulted in increased intake of fruit and whole grains and decreased intake of dairy for most diet patterns, while the effects on the intake of vegetables, protein foods, and oils were variable across diet patterns. The complexity of the natural eating environment, in which many people consume mixed dishes that include both healthy and less healthy ingredients, produces a challenge for health professionals when providing dietary counseling. Nevertheless, this substitution approach may help improve adherence to dietary guidelines, especially if used as a steppingstone for further dietary improvement.

Previous studies have not accounted for the close link between type 2 diabetes mellitus (T2DM) and obesity when investigating the impact of T2DM on cytochrome P450 (CYP) activities. The aim was to investigate the effect of T2DM on in vivo activities and protein expressions of CYP2C19, CYP3A, CYP1A2, and CYP2C9 in patients with obesity. A total of 99 patients from the COCKTAIL study (NCT02386917) were included in this cross-sectional analysis; 29 with T2DM and obesity (T2DM-obesity), 53 with obesity without T2DM (obesity), and 17 controls without T2DM and obesity (controls). CYP activities were assessed after the administration of a cocktail of probe drugs including omeprazole (CYP2C19), midazolam (CYP3A), caffeine (CYP1A2), and losartan (CYP2C9). Jejunal and liver biopsies were also obtained to determine protein concentrations of the respective CYPs. CYP2C19 activity and jejunal CYP2C19 concentration were 63% (-0.39 [95% CI: -0.82, -0.09]) and 40% (-0.09 fmol/μg protein [95% CI: -0.18, -0.003]) lower in T2DM-obesity compared with the obesity group, respectively. By contrast, there were no differences in the in vivo activities and protein concentrations of CYP3A, CYP1A2, and CYP2C9. Multivariable regression analyses also indicated that T2DM was associated with interindividual variability in CYP2C19 activity, but not CYP3A, CYP1A2, and CYP2C9 activities. The findings indicate that T2DM has a significant downregulating impact on CYP2C19 activity, but not on CYP3A, CYP1A2, and CYP2C9 activities and protein concentrations in patients with obesity. Hence, the effect of T2DM seems to be isoform-specific., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Many Americans have adopted popular diet patterns for general health improvement that restrict specific foods, macronutrients, or eating time. However, there is limited evidence to characterize the quality of these diet patterns., Objectives: This study 1 ) evaluated the quality of popular diet patterns in the United States and 2 ) modeled the effect of targeted food substitutions on diet quality., Methods: Dietary data from 34,411 adults ≥20 y old were acquired from the NHANES, 2005-2018. Dietary intake was assessed using the National Cancer Institute's usual intake methodology, and the Healthy Eating Index-2015 was used to evaluate diet quality. A diet model was used to evaluate the effect of targeted food substitutions on diet quality., Results: A pescatarian diet pattern had the highest diet quality (65.2; 95% CI: 64.0, 66.4), followed by vegetarian (63.0; 95% CI: 62.0, 64.0), low-grain (62.0; 95% CI: 61.6, 62.4), restricted-carbohydrate (56.9; 95% CI: 56.6, 57.3), time-restricted (55.2; 95% CI: 54.8, 55.5), and high-protein (51.8; 95% CI: 51.0, 62.7) diet patterns. Modeled replacement of ≤3 daily servings of foods highest in added sugar, sodium, saturated fat, and refined grains with alternative foods led to an increase in diet quality and a decrease in energy intake for most diet patterns., Conclusions: Low diet quality was observed for all popular diet patterns evaluated in this study. Modeled dietary shifts that align with recommendations to choose foods lower in added sugar, sodium, saturated fat, and refined grains led to modest improvements in diet quality and larger reductions of energy intake. Greater efforts are needed to encourage the adoption of dietary patterns that emphasize consumption of a variety of high-quality food groups., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Aim: Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls., Methods: This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations., Results: Mean ± SD weight loss from baseline was similar in the RYGB-group (13 ± 2.4%) and the diet group (10.5 ± 3.9%) at week 9, but differed at year 2 (RYGB -30 ± 6.9%, diet -3.1 ± 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference -0.30 [-0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities., Conclusion: Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4β-hydroxycholesterol (4βOHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4βOHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range., Methods: The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4βOHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam., Results: 4βOHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (ρ = 0.53, p < 0.001), and hepatic CYP3A4 concentrations (ρ = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (ρ = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (ρ = 0.15, p = 0.53). 4βOHC concentrations correlated weakly with midazolam absolute bioavailability (ρ =  - 0.23, p = 0.027) and apparent oral clearance (ρ = 0.28, p = 0.008), but not with systemic clearance (ρ =  - 0.03, p = 0.81)., Conclusion: These findings suggest that 4βOHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4βOHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs., Trial Registration: Clinical., Trials: gov identifier: NCT02386917., (© 2022. The Author(s).)

Background: The COVID-19 pandemic has highlighted the importance of mental wellbeing. The identification and implementation of quality measures can improve health outcomes and patient experience. The objective was to identify and define a core set of valid and relevant pediatric mental health quality measures that will support health system evaluation and quality improvement in British Columbia, Canada., Methods: The study consisted of four phases. First, a comprehensive database search identified valid pediatric quality measures focused on mental health and substance use (MH/SU). Second, the identified quality measures were mapped to focus areas, which were then prioritized by two stakeholder groups consisting of 26 members. Third, up to two representative measures for each prioritized focus area were pre-selected by an expert panel ( n = 9). And fourth, a three-step modified Delphi approach was employed to (1) assess each quality measure on a 7-point Likert scale against three relevance criteria (representative of a quality problem, value to intended audience and actionable), (2) discuss the results, and (3) select and rank the most relevant measures. Forty-eight stakeholders were invited to participate; of those 24 completed the round 1 survey, 21 participated in the round 2 discussion and 18 voted in the round 3 selection and ranking survey. For round 1, consensus was determined when at least 70% of the response rates were within the range of five to seven. For round 3, Kendall's coefficient of concordance W was used as an estimator of inter-rater reliability., Results: One-hundred pediatric mental health quality measures were identified in the database search. Of those, 37 were mapped to ten focus areas. Pre-selection resulted in 19 representative measures moving forward to the Delphi study. Eleven measures met the consensus thresholds and were brought forward to the round 2 discussion. Round 3 ranking showed moderate to strong raters' agreement (Kendall's W = 0.595; p < 0.01) and resulted in the following five highest-ranked measures: level of satisfaction after discharge from inpatient admission due to MH/SU, number of patients experiencing seclusion or restraint, length of time from eating disorder referral to assessment, number of ED visits due to MH/SU, and number of readmissions to ED., Conclusion: The selected core set of valid and relevant pediatric quality measures will support sustainable system change in British Columbia. The five top-ranked measures will be refined and tested for data collection feasibility before being implemented in the province., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Waibel, Wu, Smith, Johnson and Janke.)