Gut microbial diversity and functional characterization in people with alcohol use disorder: A case-control study.

Individuals with Alcohol Use Disorder (AUD) typically have comorbid chronic health conditions, including anxiety and depression disorders, increased sleep disruption, and poor nutrition status, along with gut microbial dysbiosis. To better understand the effects of gut dysbiosis previously shown in individuals with AUD, gut microbiome and metabolome were investigated between three cohorts. Two groups of individuals with AUD included treatment-seeking newly abstinent for at least six weeks (AB: N = 10) and non-treatment-seeking currently drinking (CD: N = 9) individuals. The third group was age, gender, and BMI-matched healthy controls (HC: N = 12). Deep phenotyping during two weeks of outpatient National Institutes of Health Clinical Center visits was performed, including clinical, psychological, medical, metabolic, dietary, and experimental assessments. Alpha and beta diversity and differential microbial taxa and metabolite abundance of the gut microbiome were examined across the three groups. Metabolites derived from the lipid super-pathway were identified to be more abundant in the AB group compared to CD and HC groups. The AB individuals appeared to be most clinically different from CD and HC individuals with respect to their gut microbiome and metabolome. These findings highlight the potential long-term effects of chronic alcohol use in individuals with AUD, even during short-term abstinence.

A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

The thermoneutral zone in women takes an "arctic" shift compared to men.

Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.

Youth's energy intake during a laboratory-based loss-of-control eating paradigm: Associations with reported current dieting.

Dieting is theorized as a risk factor for loss-of-control (LOC)-eating (i.e., feeling a sense of lack of control while eating). Support for this association has largely relied on retrospective self-report data, which does not always correlate with objectively assessed eating behavior in youth. We hypothesized that during a laboratory-based LOC-eating paradigm, children and adolescents who reported current (at the time of the visit) dieting would consume meals consistent with LOC-eating (greater caloric intake, and intake of carbohydrates and fats, but less intake of protein). Participants were presented with a buffet-style meal and instructed to "Let yourself go and eat as much as you want." Current dieting (i.e., any deliberate change to the amount or type of food eaten to influence shape or weight, regardless of how effective the changes are) was assessed via interview. General linear models were adjusted for fat mass (%), lean mass (kg), height, sex, protocol, race and ethnicity, pre-meal hunger and minutes since consumption of a breakfast shake. Of 337 participants (Mage 12.8 ± 2.7y; 62.3 % female; 45.7 % non- Hispanic White and 26.1 % non-Hispanic Black; MBMIz 0.78 ± 1.11), only 33 (9.8 %) reported current dieting. Current dieting was not significantly associated with total energy intake (F = 1.63, p = .20, ηp2 = 0.005), or intake from carbohydrates (F = 2.45, p = .12, ηp2 = 0.007), fat (F = 2.65, p = .10, ηp2 = 0.008), or protein (F = 0.39, p = .53, ηp2 = 0.001). Contrary to theories that dieting promotes LOC-eating, current dieting was not associated with youth's eating behavior in a laboratory setting. Experimental approaches for investigating dieting are needed to test theories that implicate dieting in pediatric LOC-eating.

Dynamic Elevation of Aromatic Amino Acids in Hepatitis C Virus-Induced Cirrhosis After a Standard Meal.

INTRODUCTION: Perturbations in aromatic (AAAs) and branched-chain amino acids (BCAAs) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, postprandial relationship between hepatitis C virus-induced liver disease and amino acid concentrations in patients with compensated liver disease. METHODS: Patients infected with hepatitis C virus underwent a baseline liver biopsy to determine Ishak Fibrosis Score and evaluate the liver transcriptome. Patients ate a standard meal and underwent peripheral vein sampling at defined intervals. Quantitative analysis of amino acids was performed using liquid chromatography-tandem mass spectrometry. RESULTS: At baseline, there was no difference in AAA and BCAA concentrations between patients with cirrhosis and non-cirrhotic patients. After a standard meal, AAAs, but not BCAAs, were elevated in patients with cirrhosis compared with non-cirrhotic patients at every time point. The HepQuant SHUNT fraction was significantly higher in patients with cirrhosis and positively correlated with AAA concentration at all time points, but not BCAA. Analysis of the hepatic transcriptome demonstrated greater downregulation of the AAA degradation pathways than the BCAA degradation pathways. DISCUSSION: At baseline, cirrhotic patients with compensated liver disease have adequate reserve liver function to metabolize AAAs and BCAAs. When faced with a metabolic stressor, such as a standard meal, patients with cirrhosis are less able to metabolize the increased load of AAAs. This impairment correlates with portosystemic shunting. Further evaluation of AAA levels in compensated liver disease might further the understanding of the liver-muscle axis and the role it may play in the development of sarcopenia in liver disease.

Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

Dietary linoleic acid lowering alone does not lower arachidonic acid or endocannabinoids among women with overweight and obesity: A randomized, controlled trial.

The linoleic acid (LA)-arachidonic acid (ARA)-inflammatory axis suggests dietary LA lowering benefits health because it lowers ARA and ARA-derived endocannabinoids (ECB). Dietary LA reduction increases concentrations of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DHA derived ECB. The aim of this study was to examine targeted reduction of dietary LA, with and without EPA and DHA, on plasma EPA and DHA and ECB (2-arachidonoyl glycerol [2-AG], anandamide [AEA], and docosahexaenoyl ethanolamide [DHA-EA]). Healthy, pre-menopausal women (n = 62, BMI 30 ± 3 kg/m2 , age 35 ± 7 years; mean ± SD) were randomized to three 12-week controlled diets: (1) high LA, low omega-3 EPA and DHA (H6L3); (2) low LA, low omega-3 EPA and DHA (L6L3); or (3) low LA, high omega-3 EPA and DHA (L6H3). Baseline plasma fatty acids and ECB were similar between diets. Starting at 4 weeks, L6L3 and L6H3 lowered plasma LA compared to H6L3 (p < 0.001). While plasma ARA changed from baseline by 8% in L6L3 and -8% in L6H3, there were no group differences. After 4 weeks, plasma EPA and DHA increased from baseline in women on the L6H3 diet (ps < 0.001) and were different than the H6L3 and L6L3 diets. No differences were found between diets for AEA or 2-AG, however, in L6L3 and L6H3, AEA increased by 14% (ps < 0.02). L6H3 resulted in 35% higher DHA-EA (p = 0.013) whereas no changes were seen with the other diets. Lowering dietary LA did not result in the expected changes in fatty acids associated with the LA-ARA inflammatory axis in women with overweight and obesity.

Neural underpinnings of threat bias in relation to loss-of-control eating behaviors among adolescent girls with high weight.

Introduction: Loss-of-control (LOC) eating, a key feature of binge-eating disorder, may relate attentional bias (AB) to highly salient interpersonal stimuli. The current pilot study used magnetoencephalography (MEG) to explore neural features of AB to socially threatening cues in adolescent girls with and without LOC-eating. Methods: Girls (12-17 years old) with overweight or obesity (BMI >85th percentile) completed an AB measure on an affective dot-probe AB task during MEG and evoked neural responses to angry or happy (vs. neutral) face cues were captured. A laboratory test meal paradigm measured energy intake and macronutrient consumption patterns. Results: Girls (N = 34; Mage = 15.5 ± 1.5 years; BMI-z = 1.7 ± 0.4) showed a blunted evoked response to the presentation of angry face compared with neutral face cues in the left dorsolateral prefrontal cortex, a neural region implicated in executive control and regulation processes, during attention deployment (p < 0.01). Compared with those without LOC-eating (N = 21), girls with LOC-eating (N = 13) demonstrated a stronger evoked response to angry faces in the visual cortex during attention deployment (p < 0.001). Visual and cognitive control ROIs had trends suggesting interaction with test meal intake patterns among girls with LOC-eating (ps = 0.01). Discussion: These findings suggest that girls with overweight or obesity may fail to adaptively engage neural regions implicated in higher-order executive processes. This difficulty may relate to disinhibited eating patterns that could lead to excess weight gain.

Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers.

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [18F]fallypride and [11C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m2). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [11C]raclopride (r= -0.51; p<0.0001) but not [18F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [18F]fallypride has greater binding affinity to dopamine type-2 receptors than [11C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.

Non-selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels.

BACKGROUND & AIMS: Direct-acting antiviral (DAA) therapy has revolutionized treatment for the hepatitis C virus (HCV). While DAA therapy is common, little is known about the intrahepatic immunological changes after sustained virologic response (SVR). We aim to describe transcriptional alterations of the gut microbiome and the liver after SVR. METHODS: Twenty-two HCV patients were evaluated before and 9 months after 12 weeks of sofosbuvir/velpatasvir treatment. All achieved SVR. A liver biopsy, portal blood (direct portal vein cannulation), peripheral blood and stool samples were obtained. RNA-seq and immunofluorescent staining were performed on liver biopsies. RNA-seq and 16S rRNA metagenomics were performed on stool. RESULTS: Differential expression within liver transcription showed 514 downregulated genes (FDR q < .05; foldchange > 2) enriched in inflammatory pathways; of note, GO:0060337, type 1 IFN signalling (p = 8e-23) and GO:0042742, defence response to bacterium (p = 8e-3). Interestingly, microbial products increased in the portal blood and liver after SVR. Due to the increase in microbial products, the gut microbiome was investigated. There was no dysbiosis by Shannon diversity index or Bacteroides/Firmicutes ratio. There was a differential increase in genes responsible for bacterial lipopolysaccharide production after SVR. CONCLUSIONS: The decrease in the antiviral interferon pathway expression was expected after SVR; however, there was an unanticipated decrease in the transcription of genes involved in recognition and response to bacteria, which was associated with increased levels of microbial products. Finally, the alterations in the function of the gut microbiome are a promising avenue for further investigation of the gut-liver axis, especially in the context of the significant immunological changes noted after SVR.

Changes in Food Consumption, BMI, and Body Composition in Youth in the US during the COVID-19 Pandemic.

Rates of childhood overweight/obesity have risen for decades; however, data show the prevalence increased at a faster rate during the COVID-19 pandemic. Pandemic-associated increases in youth's body mass index (BMI; kg/m2) have been attributed to decreases in reported physical activity; few studies have examined changes in food intake. We therefore examined changes in total energy, nutrient consumption, BMI, BMIz, and adiposity longitudinally over 3 years, comparing healthy youth aged 8-17 years assessed twice prior to the pandemic, to youth seen once before and once during the pandemic. The total energy intake and percent macronutrient consumption were assessed using a standardized, laboratory-based, buffet-style meal. Height and weight were measured and adiposity was collected via dual energy X-ray absorptiometry. Generalized linear model univariate analyses investigated differences between groups. One-hundred-fifteen youth (15.6 + 2.8 years 47.8% female; 54.8% White) from the Washington D.C., Maryland, and Virginia greater metropolitan area participated. In this secondary analysis, neither changes in total energy intake (p = 0.52) nor changes in nutrient consumption were significantly different between the two groups (ps = 0.23-0.83). Likewise, changes in BMI, BMIz, and adiposity (ps = 0.95-0.25) did not differ by group. Further research should investigate food intake and body composition, comparing youth with and without overweight/obesity to better identify those at greatest risk of excess weight gain during the pandemic.

Associated features of pediatric loss-of-control eating severity during a laboratory-based feeding paradigm.

Laboratory-based loss-of-control eating (LOC-eating; i.e., feeling like one cannot stop eating) paradigms have provided inconsistent evidence that the features of pediatric LOC-eating are consistent with those of DSM-5-TR binge-eating episodes. Thus, this study investigated whether recent LOC-eating (in the prior month) and/or greater LOC-eating severity during a meal are positively associated with faster eating rate, energy intake when adjusting for hunger, post-meal stomachache and sickness (a proxy for eating until uncomfortably full), depression, and guilt. Recent LOC-eating was assessed via interview. Participants were presented with a buffet-type meal and instructed to "Let yourself go and eat as much as you want." Immediately following, youth reported on their experience of LOC-eating during the meal (LOC-eating severity). Eating rate (kcal/min) was computed by dividing total energy intake by the duration of the meal. Prior to and following the meal, youth reported hunger, sickness, and stomachache via sliding Visual Analog Scales, depression via the Brunel Mood Scale and guilt via the PANAS-X. Three-hundred-ten youth participated (61.2 % Female; 46.3 % non-Hispanic White, 12.96 ± 2.72 y). Recent LOC-eating was not significantly associated with any DSM-5-TR binge-eating feature during the laboratory meal (ps = 0.07-0.85). However, LOC-eating severity during the meal was positively associated with eating rate, eating adjusted for hunger, post-meal sickness and stomachache, and guilt (ps < 0.045). LOC-eating severity during a laboratory-based feeding paradigm meal, but not recent LOC-eating, was associated with several features of DSM-5-TR binge-eating episodes. Future studies should assess multiple components of LOC-eating to further characterize the phenomenology of pediatric LOC-eating.

Associations of food reinforcement and food- related inhibitory control with adiposity and weight gain in children and adolescents.

Some, but not all studies have reported that, among youth with disordered eating and high weight, the relative reinforcing value of food (RRV-F, i.e., how hard a person will work for a high-energy-dense food when another reward is available) is greater, and food-related inhibitory control (i.e., ability to withhold a response to food-related stimuli) is lower, compared to peers without disordered eating or overweight. In most studies, high RRV-F and low food-related inhibitory control have been studied separately, as independent factors, with each suggested to predict excess weight and adiposity (fat mass) gain. We hypothesized that the interaction of these factors would prospectively exacerbate risk for weight and adiposity (fat mass) gain three years later in a sample of healthy youth. At baseline, RRV-F was measured using a Behavior Choice Task with the rewards being standardized servings of chocolate candies, cheese crackers, or fruit snacks. Food-related inhibitory control was determined by performance in response to food and non-food stimuli during a Food Go/No-Go task. At baseline and 3-year visits, total body adiposity was measured by dual-energy X-ray absorptiometry (DXA) and body mass index (BMI) was obtained using measured weight and height. A linear regression was conducted with 3-year adiposity as the dependent variable. RRV-F, food-related inhibitory control, and the RRV-F x food-related inhibitory control interaction as independent variables. Baseline adiposity, age, height, sex, race/ethnicity, and days between visits were included as covariates for model predicting 3-year adiposity. Baseline BMI, age, sex, race/ethnicity, and days between visits were included as covariates for model predicting 3-year BMI. One-hundred and nine youth (mean 12.4±2.7y, mean 0.50±1.02 BMIz, 30.3% with overweight/obesity, 45.9% female, 51.4% non-Hispanic White), 8-17 years at baseline, were studied. Baseline food-related inhibitory control (ßunstandardized = 0.33, p = .037, 95% CI [.02, 0.64]), but not baseline RRV-F (ßunstandardized = -0.003, p = .914), 95% CI [-0.05, 0.05]) was significantly associated with 3-year adiposity such that those with the poorest food-related inhibitory control (great number of commision errors) had the greatest adiposity gain. The interaction between RRV-F and food-related inhibitory control did not predict 3-year adiposity (ßunstandardized = -0.07, p = .648, 95% CI [-0.39, 0.25]). The pattern of findings was the same for models examining non-food related inhibitory control. Neither baseline food-related inhibitory control (ßunstandardized = 2.16, p = .256, 95% CI [-1.59, 5.92]), baseline RRV-F (ßunstandardized = 0.14, p = .660, 95% CI [-0.48, 0.75]), nor their interaction (ßunstandardized = -1.18, p = .547, 95% CI [-5.04, 2.69]) were significantly associated with 3-year BMI. However, non-food related inhibitory control (ßunstandardized = 0.54, p = .038, 95% CI [.22, 7.15]) was significantly associated with 3-year BMI. In summary, food-related inhibitory control but not RRV-F, was associated with changes in adiposity in a sample of children and adolescents. Among generally healthy youth, food-related inhibitory control may be a more relevant risk factor than food reinforcement for adiposity gain. Additional data are needed to determine how inhibitory control and reward systems, as well as other disinhibited eating behaviors/traits, may interact to promote excess weight gain over time in youth.

The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes.

Disclosure summary: Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose. Background: Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity. Objective: The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity. Methods: In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase. Results: Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m2), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo Proteobacteria, Enterobacteriaceae, and Enterobacteriales were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month. Conclusion: Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04209075.

No significant salt or sweet taste preference or sensitivity differences following ad libitum consumption of ultra-processed and unprocessed diets: a randomized controlled pilot study.

Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053.

Evaluation of a Newly Implemented Critical Thromboelastography (TEG) Value Callback System.

OBJECTIVES: Thromboelastography (TEG) measures whole blood coagulation kinetics in real time and is useful in guiding blood product transfusion. At our institution, providers have immediate remote access to TEG results. However, some critical values are occasionally missed. Our patient blood management program implemented a critical TEG value callback system to improve patient management and blood product utilization. METHODS: This retrospective, observational study assessed the data of trauma and critical care patients preimplementation (n = 20) and postimplementation (n = 100) of the callback system. Provider responses to callbacks and changes in TEG parameters after subsequent testing were compared between the two groups. RESULTS: In response to callbacks, 42% provided appropriate management and 42% ordered a repeat TEG vs 28% and 33% in the historical group (P < .0001 and P = .0002, respectively). Following callback, 90% of the TEG parameters in the study group showed an improvement vs 57% in the control group (P = .011). CONCLUSIONS: The increase in appropriate management and the improvement in TEG parameters upon repeat testing in the study group compared to the control group demonstrate the efficacy of the TEG callback system. Further studies are needed to evaluate the callback system effect on patient outcome.

Effects of interrupting daily sedentary behavior on children's glucose metabolism: A 6-day randomized controlled trial.

BACKGROUND: Metabolic disease risk in youth is influenced by sedentary behaviors. Acute in-lab studies show that, during a single day, interrupting a sedentary period with short bouts of physical activity improves glucometabolic outcomes. OBJECTIVE: To determine if acutely improved glucose metabolism persists after multi-day interruptions of sitting with walking brief bouts. We hypothesized that children who underwent interrupting sitting on multiple days would demonstrate lower insulin area under the curve during an oral glucose tolerance test compared to uninterrupted sitting. METHODS: Healthy, normoglycemic children (N = 109) ages 7-11 years were randomized to one of two conditions: Control (3 h of daily Uninterrupted Sitting) or Interrupted Sitting (3-min of moderate-intensity walking every 30 min for 3 h daily); with dietary intake controlled through provision of foodstuffs for the entire experiment. Participants attended six consecutive daily visits at a research ambulatory unit. The primary outcome was insulin area under the curve during the oral glucose tolerance test on day 6 during interrupted or uninterrupted sitting; secondary outcomes included glucose and c-peptide area under the curve, energy intake at a buffet meal on day 6, and free-living activity. RESULTS: Among 93 children (42 uninterrupted sitting, 51 interrupted sitting), daily interrupted sitting resulted in 21% lower insulin (ß = 0.102 CI:0.032-0.172, p = 0.005) and a 10% lower C-peptide (ß = 0.043, CI:0.001-0.084, p = 0.045) area under the curve. Matsuda and Glucose Effectiveness Indices were also improved (p's < 0.05). There were no group differences in energy intake or expenditure. CONCLUSIONS: Sustained behavioral change by interrupting sedentary behaviors is a promising intervention strategy for improving metabolic risk in children.

Heart Rate Variability and Laboratory-Based Loss-of-Control Eating in Children and Adolescents.

Among youth, greater heart rate (HR) and lesser HR variability (HRV) are precursors to loss-of-control (LOC) eating episodes in the natural environment. However, there are limited data examining whether pre-meal HR and HRV are associated with greater LOC-eating in the laboratory setting. We therefore examined temporal relationships between pre-meal HR, frequency- and time-based metrics of pre-meal HRV, perceived LOC-eating, and energy intake during a meal designed to simulate a LOC-eating episode. Among 209 participants (54.5% female, 12.58 ± 2.72 years, 0.52 ± 1.02 BMIz), 19 reported LOC-eating in the prior month. Perceived LOC-eating during the laboratory meal was not significantly linked to pre-meal HR (p = 0.37), but was positively related to pre-meal HRV (ps = 0.02-0.04). This finding was driven by youth with recent LOC-eating, as these associations were not significant when analyses were run only among participants without recent reported LOC-eating (p = 0.15-0.99). Pre-meal HR and HRV were not significantly related to total energy intake (ps = 0.27-0.81). Additional research is required to determine whether early-stage pediatric LOC-eating is preceded by a healthy pre-meal stress response. Longitudinal studies could help clarify whether this pattern becomes less functional over time among youth who develop recurrent LOC-eating episodes.

Dietary Intakes of Patients with Alcohol Use Disorder During a 4-Week Protocol on an Inpatient Treatment Unit Found to Meet Dietary Reference Intakes for Macronutrients, but Have Variability in Energy Balance and Adequacy of Micronutrient Intake.

BACKGROUND: Despite literature supporting the importance of diet during rehabilitation, minimal research quantifies dietary intake during treatment for alcohol use disorder (AUD). OBJECTIVE: The aim was to quantify dietary intake and energy balance of patients with AUD during inpatient treatment. DESIGN: This was a secondary analysis of data from a 4-week observational protocol. Participants self-selected food from a room service menu. Dietary intake was recorded by patients and reviewed by nutrition staff. To quantify nutrient and food group intake, data were coded into Nutrition Data Systems for Research software, versions 2016 and 2017. Daily average intake was calculated for all dietary variables. PARTICIPANTS/SETTING: Participants (n = 22) were adults seeking treatment for AUD at the National Institutes of Health Clinical Center (Bethesda, MD) between September 2016 and September 2017 and who were enrolled in a study examining the microbiome during AUD rehabilitation. Four participants discontinued protocol participation before study week 4 and were not included in analyses examining change over time. MAIN OUTCOME MEASURES: Weight change, daily energy, and macronutrient and select micronutrient intakes were the main outcome measures included. STATISTICAL ANALYSES PERFORMED: Mean differences in intake and weight were assessed using nonparametric tests. RESULTS: Sixty-four percent of participants were male; mean ± SD age was 46.3 ± 13.0 years, mean ± SD body mass index (calculated as kg/m2) was 23.9 ± 2.5, and mean intake was 2,665 kcal/d (consisting of 45.9% carbohydrate, 34.9% fat, and 19.1% protein). Eighty percent or more of this sample met the Estimated Average Requirement for 10 of 16 micronutrients assessed. Male participants consumed more energy than estimated needs (P = .003) and gained a mean ± SD of 2.67 ± 1.84 kg (P = .006) when an outlier with weight loss and acute pancreatitis was removed from analysis. Female participants did not gain weight or consume more than estimated energy needs. CONCLUSIONS: Overall macronutrient intake was within recommended ranges, but intake of other dietary components and weight gain were variable, supporting the need for individualized nutrition care during AUD treatment.

Postprandial Plasma Lipidomics Reveal Specific Alteration of Hepatic-derived Diacylglycerols in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD. METHODS: In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model. RESULTS: There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids. CONCLUSIONS: We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.