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.

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.

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.

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.

Death-associated protein kinase 3 regulates the myogenic reactivity of cerebral arteries.

NEW FINDINGS: What is the central question of this study? DAPK3 contributes to the Ca2+ -sensitization of vascular smooth muscle contraction: does this protein kinase participate in the myogenic response of cerebral arteries? What is the main finding and its importance? Small molecule inhibitors of DAPK3 effectively block the myogenic responses of cerebral arteries. HS38-dependent changes to vessel constriction occur independent of LC20 phosphorylation, and therefore DAPK3 appears to operate via the actin cytoskeleton. A role for DAPK3 in the myogenic response was not previously reported, and the results support a potential new therapeutic target in the cerebrovascular system. ABSTRACT: The vascular smooth muscle (VSM) of resistance blood vessels is a target of intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In the brain, the myogenic reactivity of cerebral arteries is critical to homeostatic blood flow regulation. Here we provide the first evidence to link the death-associated protein kinase 3 (DAPK3) to the myogenic response of rat and human cerebral arteries. DAPK3 is a Ser/Thr kinase involved in Ca2+ -sensitization mechanisms of smooth muscle contraction. Ex vivo administration of a specific DAPK3 inhibitor (i.e., HS38) could attenuate vessel constrictions invoked by serotonin as well as intraluminal pressure elevation. The HS38-dependent dilatation was not associated with any change in myosin light chain (LC20) phosphorylation. The results suggest that DAPK3 does not regulate Ca2+ sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. A slow return of myogenic tone was observed during the sustained ex vivo exposure of cerebral arteries to HS38. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signalling compensation in response to attenuation of DAPK3 activity. Additional experiments with VSM cells revealed HS38- and siDAPK-dependent effects on the actin cytoskeleton and focal adhesion kinase phosphorylation status. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38-dependent attenuation of myogenic reactivity found for human pial vessels.

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.

Smoothelin-like 1 knockout mice display sex-dependent alterations in blood flow and cardiac function.

Smoothelin-like 1 (SMTNL1) modulates the contractile performance of smooth muscle and thus has a key role in vascular homeostasis. Elevated vascular tone, recognized as a contributor to the development of progressive cardiac dysfunction, was previously found with SMTNL1 deletion. In this study, we assessed cardiac morphology and function of male and female, wild-type (Smtnl1+/+) and global SMTNL1 knockout (Smtnl1-/-) mice at 10 weeks of age. Gross dissection revealed distinct cardiac morphology only in males; Smtnl1-/- hearts were significantly smaller than Smtnl1+/+, but the left ventricle (LV) proportion of heart mass was greater. Male Smtnl1-/- mice also displayed increased ejection fraction and fractional shortening, as well as elevated aortic and pulmonary flow velocities. The impact of cardiac stress with pressure overload by transverse aortic constriction (TAC) was examined in male mice. With TAC banding, systolic function was preserved, but the LV filling pressure was selectively elevated due to relaxation impairment. Smtnl1-/- mice displayed higher early/passive filling velocity of LV/early mitral annulus velocity ratio (E/E' ratio) and myocardial performance index along with a prolonged isovolumetric relaxation time. Taken together, the findings support a novel, sex-dimorphic role for SMTNL1 in modulating cardiac structure and function of mice.

Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab.

PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P < 0.01) and reduction in ocular motility restriction ( P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

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.

Hyperbaric Oxygen Therapy after Mid-Cervical Spinal Contusion Injury.

Hyperbaric oxygen (HBO) therapy is frequently used to treat peripheral wounds or decompression sickness. Evidence suggests that HBO therapy can provide neuroprotection and has an anti-inflammatory impact after neurological injury, including spinal cord injury (SCI). Our primary purpose was to conduct a genome-wide screening of mRNA expression changes in the injured spinal cord after HBO therapy. An mRNA gene array was used to evaluate samples taken from the contused region of the spinal cord following a lateralized mid-cervical contusion injury in adult female rats. HBO therapy consisted of daily, 1-h sessions (3.0 ATA, 100% O2) initiated on the day of SCI and continued for 10 days. Gene set enrichment analyses indicated that HBO upregulated genes in pathways associated with electron transport, mitochondrial function, and oxidative phosphorylation, and downregulated genes in pathways associated with inflammation (including cytokines and nuclear factor kappa B [NF-κB]) and apoptotic signaling. In a separate cohort, spinal cord histology was performed to verify whether the HBO treatment impacted neuronal cell counts or inflammatory markers. Compared with untreated rats, there were increased NeuN positive cells in the spinal cord of HBO-treated rats (p = 0.004). We conclude that HBO therapy, initiated shortly after SCI and continued for 10 days, can alter the molecular signature of the lesioned spinal cord in a manner consistent with a neuroprotective impact.

Rapid Adaptation of Cancer Education in Response to the COVID-19 Pandemic: Evaluation of a Live Virtual Statistics and Research Skills Workshop for Oncology Trainees.

Due to COVID-19, an annual interactive statistics and research methodology workshop for radiation oncology trainees was adapted at short notice into a live virtual format. This study aimed to evaluate trainee opinions around the educational value of the workshop, logistical aspects and impact on interactivity. A post-course on-line survey was completed by 26/42 trainee attendees (response rate 62%). For five pre-specified learning outcomes (LO), 58 to 69% of trainees agreed that the LO was completely or largely met (Likert scores 6 and 7 on a scale 1 = not met at all; 7 = completely met). All trainees felt that logistical aspects of the workshop including organisation, accessibility to the platform and sound/image quality were good or excellent. With regard to opportunities for interaction and suitability for small-group 'break-out' sessions, the majority felt that interaction could be adequately maintained whilst just under a quarter felt the delivery method was not fit for the purpose. Networking/social engagement with peers and teachers was the factor most impaired using the live virtual delivery format. Over three-quarters of trainees replied they would favour the current event or other educational sessions being offered (at least as an option) in a virtual format in the future. Cost and convenience were given as the major non-COVID-19-related benefits of virtual on-line learning. These preliminary findings provide valuable feedback to help adapt or develop further on-line educational and training initiatives that will be necessary in the COVID-19 pandemic period and beyond.

Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents.

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower "wanting" and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.

Engaging Multiple Worldviews With Quantitative Decision Support: A Robust Decision-Making Demonstration Using the Lake Model.

Many of today's most pressing policy challenges are usefully characterized as wicked problems. With contested framings parties to a decision disagree not only on potential solutions, but on the nature of the problem they are trying to solve. The quantitative tools of risk and policy analysis, commonly designed to develop and compare choices within a single decision framing, are poorly designed to bring quantitative information into debates with contested framings. This study aims to build on recent advances in decision making under deep uncertainty (DMDU) to demonstrate methods and tools that may help resolve the tension between quantitative decision support and multiworldview approaches for addressing wicked problems. The study employs robust decision making (RDM), one common DMDU method, and a new version of the lake model, a simple and widely used model of a coupled human and natural system, to conduct a stylized analysis that reflects three different worldviews. The RDM analysis solves the decision challenge independently for each worldview and then compares each set of solutions from the vantage of the other worldviews. The resulting utopia-dystopia matrix informs problem reframing that seeks robust, adaptive strategies independently consistent with each worldview and thus provides a locus for agreement. The study describes how stakeholder engagements might use such analytic tools and their information products to provide overlapping but alternative entry points for groups with fundamentally different worldviews to engage with each other in deliberative processes appropriate for wicked problems.