A longitudinal observational study of skeletal development between ages 3 mo and 6 y in children fed human milk, milk formula, or soy formula.

BACKGROUND: Early infant feeding can affect skeletal development. Most children are fed with breast milk, dairy-based infant formula, or soy-based infant formula during the first year of life. The National Health and Nutrition Examination Survey 2003-2010 reports that 12% of the US infants consume soy-based infant formula. Despite potential effects of soy-associated isoflavones on skeletal development, studies investigating bone metabolism and structural and functional bone indices in children are lacking. OBJECTIVE: The aim of this observational study was to investigate early effects of soy-based infant formula (SF group) intake on bone metabolism and structure during the first 6 y of life comparing with those of infants fed with breast milk (BF group) and dairy-based infant formula (MF group). METHODS: A total of 433 healthy infants were followed up from 3 mo to 6 y of age. Children's skeletal development was assessed using dual-energy X-ray absorptiometry (DXA; N = 433) and peripheral quantitative computed tomography (pQCT; n = 78). The urinary biomarkers of bone metabolism (N-terminal telopeptide of type I collagen [NTx] and osteocalcin) were evaluated using immunoassays at 6, 24, 60, and 72 mo. RESULTS: No statistically significant group differences were observed in bone mineral density (BMD) between the BF, MF, and SF groups, assessed using DXA or pQCT. At 6 y of age, children in the SF group showed significantly greater whole-body bone mineral content measured using DXA than those in the MF group. Six-month-old boys in the SF group demonstrated significantly greater levels of NTx than those in the MF group and significantly greater osteocalcin levels than those in the BF group. CONCLUSIONS: Together, these data suggest that although infants at age 6 mo in the SF group showed some enhanced bone metabolism compared with those in the BF and MF groups, as indicated by the urinary biomarkers, no differences in bone metabolism or BMD were noted between ages 2 and 6 y. This trial was registered at clinicaltrials.gov as NCT00616395.

Associations Between Maternal Physical Activity, Maternal Lipid Levels, and Infant Anthropometric Outcomes at Two Weeks of Age.

BACKGROUND: This study determined the relationship between physical activity (PA), circulating lipids throughout pregnancy and infant anthropometric outcomes at birth and 2 weeks of age. METHODS: Women (N = 234) with normal weight (NW, BMI 18.5-24.9 kg/m2) and with overweight and class I obesity (OW/OB, BMI 25-35 kg/m2) were categorized into high and low PA based on average cohort steps during pregnancy (8099 steps/day). Circulating fasting lipids were measured at each trimester. Standardized methods were used to obtain anthropometrics measures. Infant body composition was estimated by quantitative nuclear magnetic resonance (EchoMRI-AH small; ECHO Medical Systems). RESULTS: Women with NW who had higher activity had lower circulating triglycerides (TG) and total cholesterol (TC) levels at 12 weeks compared to women with NW and low activity (p < 0.05). Women with OW/OB and high activity level throughout pregnancy had lower circulating TG, and low density lipoprotein (LDL), at 12 weeks, lower LDL at 24 weeks, and lower TG at 36 weeks compared to the women with OW/OB who had low activity levels (p < 0.05). For children born to women with OW/OB, maternal circulating TG and LDL were most associated with infant anthropometrics at 2 weeks of age. CONCLUSION: This study supports that higher PA during pregnancy is associated with lower lipid levels throughout pregnancy with a greater effect size in women with OW/OB. Maternal lipids were associated with anthropometrics and infant body composition at two weeks of life in women with OW/OB.

Effect of Obesity on Arithmetic Processing in Preteens With High and Low Math Skills: An Event-Related Potentials Study.

Preadolescence is an important period for the consolidation of certain arithmetic facts, and the development of problem-solving strategies. Obese subjects seem to have poorer academic performance in math than their normal-weight peers, suggesting a negative effect of obesity on math skills in critical developmental periods. To test this hypothesis, event-related potentials (ERPs) were collected during a delayed-verification math task using simple addition and subtraction problems in obese [above 95th body mass index (BMI) percentile] and non-obese (between 5th and 90th BMI percentile) preteens with different levels of math skill; thirty-one with low math skills (14 obese, mean BMI = 26.40, 9.79 years old; 17 non-obese, BMI = 17.45, 9.76 years old) and thirty-one with high math skills (15 obese, BMI = 26.90, 9.60 years old; 16 non-obese, BMI = 17.13, 9.63 years old). No significant differences between weight groups were observed in task accuracy regardless of their mathematical skill level. For ERPs, electrophysiological differences were found only in the subtraction condition; participants with obesity showed an electrophysiologic pattern associated with a reduced ability to allocate attention resources regardless of their math skill level, these differences were characterized by longer P300 latency than their normal-weight peers. Moreover, the participants with obesity with high math skills displayed hypoactivity in left superior parietal lobule compared with their normal-weight peers. Additionally, obese preteens with low math skills displayed smaller arithmetic N400 amplitude than non-obese participants, reflecting difficulties in retrieving visual, semantic, and lexical information about numbers. We conclude that participants with obesity are less able than their normal-weight peers to deploy their attention regardless of their behavioral performance, which seems to have a greater effect on obese participants with low math skills because they also show problems in the retrieval of solutions from working memory, resulting in a delay in the development of mathematical skills.

Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways.

Better biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n = 28) and nonsurvivors (n = 30) of acetaminophen-induced ALF from the NIH-sponsored Acute Liver Failure Study Group and from control volunteers (n = 10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom alanine aminotransferase was lower on day 1 than day 3, indicating a time point before peak injury (n = 10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1682 quantifiable proteins, 361 were ≥ 4-fold elevated or decreased in ALF patients versus controls and 16 of those were further elevated or decreased ≥ 4-fold in nonsurvivors versus survivors, indicating potential to predict death. Interestingly, 1 of the biomarkers was lactate dehydrogenase (LDH), which is already measured in most clinical laboratories. To validate our proteomics results and to confirm the prognostic potential of LDH, we measured LDH activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the nonsurvivors versus survivors on both days. In addition, it had prognostic value similar to the model for end-stage liver disease and outperformed the King's College Criteria, while a combination of model for end-stage liver disease and LDH together outperformed either alone. Finally, bioinformatics analysis of our proteomics data revealed alteration of numerous signaling pathways that may be important in liver regeneration. Overall, we conclude LDH can predict death in APAP-induced ALF.

Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice.

Myoglobin (Mb) is a regulator of O2 bioavailability in type I muscle and heart, at least when tissue O2 levels drop. Mb also plays a role in regulating cellular nitric oxide (NO) pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggest additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance, and insulin sensitivity in Mb knockout (Mb-/-) and wild-type (WT) mice challenged with a high-fat diet (HFD, 45% of calories). In males (n = 10/genotype) and females (n = 9/genotype) tested at 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10°C, 72 h), and glucose and insulin tolerance, were not different compared with within-sex WT controls. At ∼18 and ∼19 wk of age, female Mb-/- adiposity was ∼42%-48% higher versus WT females (P = 0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb-/-, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb-/- mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.NEW & NOTEWORTHY The roles of myoglobin remain to be elaborated. We address sexual dimorphism in terms of outcomes in response to the loss of myoglobin in knockout mice and perform, for the first time, a series of comprehensive metabolic studies under conditions in which fat is mobilized (high-fat diet, cold). The results highlight that myoglobin is not necessary and sufficient for maintaining oxidative metabolism and point to alternative roles for this protein in muscle and heart.

Effect of obesity on inhibitory control in preadolescents during stop-signal task. An event-related potentials study.

Preadolescence is a period in which structural and functional changes occur in brain network reorganization that relate to the development of executive control functions, particularly in the areas of attention and cognitive inhibition. Obesity has been associated with a deficit in executive functions and behavioral and electrophysiological differences using the go/no-go task (proactive inhibition), but no study has assessed brain-electrical activity using the stop-signal task (reactive inhibition) in this population. Therefore, we hypothesized that obese preadolescents would show less efficiency in reactive inhibition than their same-age non-obese peers. To test this hypothesis, event-related potentials (ERPs) were collected during a stop-signal task and compared between 27 obese preadolescents (mean BMI = 25.9; 9.65 years old) and 29 normal-weight preadolescents (mean BMI = 17.5; 9.60 years old). No significant differences between groups were observed in behavioral responses. As for ERPs, the obese group had an electrophysiological pattern associated with less efficient conflict monitoring during the "no-go" condition (i.e., less modulation of N200 latency based on the experimental condition), differences in attentional allocation in the "go" condition (less modulation of P300a latency based on experimental condition), and difficulties in rule retrieval from working memory associated with the trial-type in both experimental conditions (smaller P300b amplitude). We conclude that obese preadolescents displayed less ability to modulate conflict-monitoring in the "no-go" condition and attention allocation in the "go" condition, evidencing differences between groups in the development of attention and inhibitory control.

Impact of Attitudes and Rurality on Veterans' Use of Veterans Health Administration Mental Health Services.

OBJECTIVE: Veterans, especially those residing in rural areas, continue to underutilize mental health care. This longitudinal study assessed attitudes relevant to seeking mental health care services from the Veterans Health Administration (VHA) over 12 months, adjusting for residence. METHODS: A questionnaire addressing attitudes, sociodemographic factors, residence, place identity, perceived health status and needs, and structural barriers was administered by telephone to 752 veterans with previous VHA service use. Service use data were obtained from a VHA database. RESULTS: In adjusted models, four attitudes were significantly associated with underuse of VHA mental health care (no use vs. any use; no use vs. nonsustained use vs. sustained use). Higher levels of mistrust of others (adjusted odds ratio [AOR]=1.06, p=0.046), emotional stoicism (AOR=1.08, p=0.003), belief in the self-resolving nature of mental health problems (AOR=1.91, p=0.015), and belief in the efficacy of religious counseling for such problems (AOR=1.09, p=0.022) were associated with no subsequent service use versus any use. Place identity (suburban), older age, and greater need were associated with greater odds of VHA use. For the comparison of no use versus sustained use, women had lower odds of no use (AOR=0.49, p<0.001); similarly, women had lower odds of nonsustained use versus sustained use (AOR=0.45, p<0.001). CONCLUSIONS: The association of potentially modifiable attitudes with underuse of VHA mental health services suggests that attitudes offer useful targets for efforts to increase mental health care use. That these attitudes were influential regardless of residence suggests that programs addressing attitudinal barriers can be broadly targeted.

Early infant feeding effect on growth and body composition during the first 6 years and neurodevelopment at age 72 months.

BACKGROUND: This study longitudinally characterized the developmental status, growth, and body composition of children who were fed human milk (breastfed, BF), cow's milk-based (MF), or soy protein-based (SF) infant formula from 3 to 12 months. METHODS: Standardized anthropometrics and dual-energy X-ray absorptiometry were used to characterize growth and body composition at 3, 6, 9, 12, 24, 36, 48, 60, and 72 months (NCT00616395). Preschool Language Scale-3, Children's Memory Scale Index (CMS), and Wechsler Preschool and Primary Scale of Intelligence were administered at age 72 months. Mixed-effects models adjusting for gestational age, birth weight, child race and sex, parental education, and maternal IQ were performed. RESULTS: Body Mass index (BMI) was significantly lower between 24 and 72 months in BF children compared to SF children. At 3 and 6 months, BF infants had significantly higher fat mass (FM) than SF infants, whereas BF children had significantly lower FM at 36 and 48 months than SF children. Delayed Recognition Index of the CMS was higher for SF than for MF participants (p = 0.009). There was no other significant difference in developmental outcomes between groups. CONCLUSIONS: In conclusion, BF, MF, and SF support adequate growth and development up to age 6 years. IMPACT: Although soy protein-based infant formula is reported to support normal infant growth and development compared to cow's milk-based formula and human milk, there are limited data on the effect of these feeding methods in school-aged children. This study suggests a significant difference in body composition, specifically BMI, after 24 months between infant feeding methods during the first year of life and in early childhood; however, all diets provide adequate nutrients to maintain normal development up to 72 months.

Impact of Student-Run Free Clinics in Urgent Care.

As Emergency Departments (EDs) become increasingly crowded, the non-urgent use of EDs exacerbates this problem. Uninsured patients have the highest percentage of non-urgent ED visits and free healthcare clinics provide access to care for the uninsured. This study analyzed the patient population of the 12th Street Health and Wellness Center (HWC), a student-run free clinic (SRFC), to understand the impact of SRFCs in urgent care. 2024 return and new patient intake forms from the HWC were analyzed. Multivariable logistic regression was performed to see which factors from the patient intake forms increase the probability that a patient came will into the clinic for urgent care. About 10% of the HWC patient population uses the clinic for emergencies, of which, 94% of them were not referred to the ED. If the HWC was not available, most of these uninsured individuals would have gone to an ED and incurred an estimated total cost of $39,515.80 in 2019. Multivariable logistic regression indicated that patients that came via walk-in are significantly more likely to seek urgent care at the clinic. Further, patients without insurance and patients who need a Spanish interpreter have a higher tendency to seek urgent care at this clinic. SRFCs save their surrounding EDs thousands of dollars in non-urgent ED visits. SRFCs should be attentive to patients who come in without an appointment, without insurance, and who need a Spanish interpreter because they are more likely to come in for an emergency.

Coupling of energy intake and energy expenditure across a temperature spectrum: impact of diet-induced obesity in mice.

Obesity and its metabolic sequelae are implicated in dysfunction of the somatosensory, sympathetic, and hypothalamic systems. Because these systems contribute to integrative regulation of energy expenditure (EE) and energy intake (EI) in response to ambient temperature (Ta) changes, we hypothesized that diet-induced obesity (DIO) disrupts Ta-associated EE-EI coupling. C57BL/6N male mice were fed a high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for ∼9.5 wk; HFD mice were then split into body weight (BWT) quartiles (n = 8 each) to study DIO-low gainers (Q1) versus -high gainers (Q4). EI and indirect calorimetry (IC) were measured over 3 days each at 10°C, 20°C, and 30°C. Responses did not differ between LFD, Q1, and Q4; EI and BWT-adjusted EE increased rapidly when transitioning toward 20°C and 10°C. In all groups, EI at 30°C was not reduced despite lower EE, resulting in positive energy balance and respiratory exchange ratios consistent with increased de novo lipogenesis, energy storage, and relative hyperphagia. We conclude that 1) systems controlling Ta-dependent acute EI/EE coupling remained intact in obese mice and 2) rapid coupling of EI/EE at cooler temperatures is an important adaptation to maintain energy stores and defend body temperature, but less critical at thermoneutrality. A post hoc analysis using digestible EI plus IC-calculated EE suggests that standard IC assumptions for EE calculation require further validation in the setting of DIO. The experimental paradigm provides a platform to query the hypothalamic, somatosensory, and sympathetic mechanisms that drive Ta-associated EI/EE coupling.

Dietary Protein Intake during Pregnancy Is Not Associated with Offspring Insulin Sensitivity during the First Two Years of Life.

Literature describing a relationship between dietary protein intake during pregnancy and offspring insulin resistance are equivocal perhaps because of the lapse between maternal and offspring measurements (~9-40 years). Thus, we evaluated protein intake in healthy women [n = 182, mean ± SD; body mass index (BMI): 26.2 ± 4.2 kg/m2] in early pregnancy (8.4 ± 1.6 weeks, EP), late pregnancy (30.1 ± 0.4 weeks, LP), and averaged throughout pregnancy, and determined the relationship between protein intake and offspring homeostatic model assessment of insulin resistance (HOMA2-IR) at 12 (12mo) and 24 (24mo) months. EP protein (g·kg-1·day-1) did not associate with HOMA2-IR at 12mo (ß = 0.153, p = 0.429) or 24mo (ß = -0.349, p = 0.098). LP protein did not associate with HOMA2-IR at 12mo (ß = 0.023, p = 0.916) or 24mo (ß = -0.442, p = 0.085). Finally, average protein did not associate with HOMA2-IR at 12mo (ß = 0.711, p = 0.05) or 24mo (ß = -0.445, p = 0.294). Results remained unchanged after adjusting for plant protein intake quartiles during pregnancy, maternal BMI, and offspring sex and body fat percentage. Additionally, these relationships did not change after quartile analysis of average protein intake, even after considering offspring fasting time and HOMA2-IR outliers, and maternal under-reporters of energy intake. Protein intake during pregnancy is not associated with indirect measurements of insulin sensitivity in offspring during the first two years of life.

Obesity Status Affects the Relationship Between Protein Intake and Insulin Sensitivity in Late Pregnancy.

The purpose of this study was to determine the associations between amount and type of dietary protein intake and insulin sensitivity in late pregnancy, in normal weight and overweight women (29.8 ± 0.2 weeks gestation, n = 173). A 100-gram oral glucose tolerance test (OGTT) was administered following an overnight fast to estimate the metabolic clearance rate of glucose (MCR, mg · kg-1 · min-1) using four different equations accounting for the availability of blood samples. Total (TP), animal (AP), and plant (PP) protein intakes were assessed using a 3-day food record. Two linear models with MCR as the response variable were fitted to the data to estimate the relationship of protein intake to insulin sensitivity either unadjusted or adjusted for early pregnancy body mass index (BMI) because of the potential of BMI to influence this relationship. There was a positive association between TP (ß = 1.37, p = 0.002) and PP (ß = 4.44, p < 0.001) intake in the last trimester of pregnancy and insulin sensitivity that weakened when accounting for early pregnancy BMI. However, there was no relationship between AP intake and insulin sensitivity (ß = 0.95, p = 0.08). Therefore, early pregnancy BMI may be a better predictor of insulin sensitivity than dietary protein intake in late pregnancy.

Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration.

The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury-acetaminophen (APAP)-in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury-the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity.

Measuring Health Spillover Effects in Caregivers of Children with Autism Spectrum Disorder: A Comparison of the EQ-5D-3L and SF-6D.

BACKGROUND AND OBJECTIVE: Healthcare interventions that improve the health of children with autism spectrum disorder (ASD) have the potential to affect the health of caregivers. This study compares the three-level EuroQoL-5 Dimension (EQ-5D-3L) and the Short Form-6 Dimension (SF-6D) in their ability to value such spillover effects in caregivers. METHODS: Clinical data collected from two Autism Treatment Network (ATN) sites was combined with survey data of caregivers of children diagnosed with ASD. Caregivers completed instruments by proxy describing child health and completed the EQ-5D-3L and SF-6D preference-weighted instruments to describe their own health. RESULTS: There was a strong correlation between the health utility scores of the two preference-weighted instruments (ρ = 0.6172, p < 0.001) measuring caregiver health-related quality of life. There was a similar correlation between both the SF-6D and EQ-5D-3L scores with a previously validated care-related quality of life measure (Care-related Quality of Life instrument [CarerQol-7D]) (ρ = 0.569, p < 0.001 and ρ = 0.541, p < 0.001, respectively). The mean SF-6D scores for caregivers differed significantly in relation to four of the five child health or behavior measures whereas the EQ-5D-3L differed for only two of them. CONCLUSIONS: Health utility values of caregivers for children with ASD vary by the health characteristics of the child, suggesting significant potential for spillover effects. The comparison of the EQ-5D-3L and SF-6D demonstrated that both instruments can be used to estimate spillover effects of interventions to improve child health, but the SF-6D exhibited greater sensitivity to child health among children with ASD.

A One-Year Institutional View of Resident Physician Burnout.

OBJECTIVES: This prospective study explores the prevalence, associated characteristics, and trajectory of burnout over one academic year in a multidisciplinary sample of resident physicians using a relatively new burnout survey instrument. METHODS: All residents from a U.S. academic health center (n = 633) were invited to complete the Copenhagen Burnout Inventory (CBI) three times, with 4-month time lags between invitations. A total of 281 (44%) provided complete CBI survey responses at least once, and 43 (7%) did at all three times. Descriptive statistics, cross-sectional analyses, correlations, and multivariable linear regression analyses were computed, as well as repeated measures ANOVAs and paired t tests, as appropriate, for each CBI domain (personal, work, patient-related burnout). RESULTS: About half had CBI scores indicating moderate-to-high levels of personal burnout (49-52%) and work-related burnout (45-49%), whereas patient-related burnout was less common (14-24%). However, patient-related burnout increased significantly from the beginning to the end of the year. Regression analyses indicated patient-related burnout was significantly higher for postgraduate year 1-2 residents compared to PGY 4+ residents, but was not significantly different by gender. Personal and work burnout scores were significantly higher for females. Persistently high burnout was observed in only 6% of respondents. CONCLUSIONS: In this study of resident physicians using the CBI, burnout was prevalent and higher levels of burnout were observed for females on the personal and work burnout domains, while junior residents had higher patient-related burnout. Persistently, high burnout was rare. The CBI demonstrated high reliability, was practical to administer, and produced similar results with existing burnout research.

Heart Rate Variability and Cognitive Bias Feedback Interventions to Prevent Post-deployment PTSD: Results from a Randomized Controlled Trial.

Introduction: There is a long history of pre-deployment PTSD prevention efforts in the military and effective pre-deployment strategies to prevent post-deployment PTSD are still needed. Materials and Methods: This randomized controlled trial included three arms: heart rate variability biofeedback (HRVB), cognitive bias modification for interpretation (CBM-I), and control. The hypothesis was that pre-deployment resilience training would result in lower post-deployment PTSD symptoms compared with control. Army National Guard soldiers (n = 342) were enrolled in the Warriors Achieving Resilience (WAR) study and analyzed. The outcome was PTSD symptom severity using the PTSD Checklist - Military version (PCL) measured at pre-deployment, 3- and 12-month post-deployment. Due to the repeated measures for each participant and cluster randomization at the company level, generalized linear mixed models were used for the analysis. This study was approved by the Army Human Research Protection Office, Central Arkansas Veterans Healthcare System Institutional Review Board (IRB), and Southeast Louisiana Veterans Health Care System IRB. Results: Overall, there was no significant intervention effect. However, there were significant intervention effects for subgroups of soldiers. For example, at 3-months post-deployment, the HRVB arm had significantly lower PCL scores than the control arm for soldiers with no previous combat zone exposure who were age 30 and older and for soldiers with previous combat zone exposure who were 45 and older (unadjusted effect size -0.97 and -1.03, respectively). A significant difference between the CBM-I and control arms was found for soldiers without previous combat zone exposure between ages 23 and 42 (unadjusted effect size -0.41). Similarly, at 12-months post-deployment, the HRVB arm had significantly lower PCL scores in older soldiers. Conclusion: Pre-deployment resilience training was acceptable and feasible and resulted in lower post-deployment PTSD symptom scores in subgroups of older soldiers compared with controls. Strengths of the study included cluster randomization at the company level, use of iPod device to deliver the resilience intervention throughout the deployment cycle, and minimal disruption of pre-deployment training by using self-paced resilience training. Weaknesses included self-report app use, study personnel not able to contact soldiers during deployment, and in general a low level of PTSD symptom severity throughout the study. In future studies, it would important for the study team and/or military personnel implementing the resilience training to be in frequent contact with participants to ensure proper use of the resilience training apps.

Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments.

Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging clinical problem. In this study, we investigated the liver and heart toxicity of HDS OxyELITE-PRO™ New Formula (OEP-NF), a dietary supplement marketed for weight loss and performance enhancement that was recently withdrawn from the market. Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and hepatotoxic risks following both short- and long-term administration schedules. Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in 40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF for eight weeks, while not exhibiting significant effects on body weights, significantly altered hepatic gene expression, increased the number of apoptotic and mast cells in the heart and affected cardiac function. The degree of toxicity in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of other hepato- and cardiotoxicity cases associated with HDS ingestion, argue strongly for introduction of quality standards and pre-marketing safety assessments for multi-ingredient HDS.

Safety assessment of the dietary supplement OxyELITE™ Pro (New Formula) in inbred and outbred mouse strains.

Herbal dietary supplements have gained wide acceptance as alternatives to conventional therapeutic agents despite concerns regarding their efficacy and safety. In 2013, a spate of severe liver injuries across the United States was linked to the dietary supplement OxyELITE Pro-New Formula (OEP-NF), a multi-ingredient product marketed for weight loss and exercise performance enhancement. The principal goal of this study was to assess the hepatotoxic potential of OEP-NF in outbred and inbred mouse models. In an acute toxicity study, significant mortality was observed after administering 10X and 3X mouse-equivalent doses (MED) of OEP-NF, respectively. Increases in liver/body weight ratio, ALT and AST were observed in female B6C3F1 mice after gavaging 2X and 1.5X MED of OEP-NF. Similar findings were observed in a 90-day feeding study. These alterations were paralleled by altered expression of gene- and microRNA-signatures of hepatotoxicity, including Cd36, Nqo1, Aldoa, Txnrd1, Scd1 and Ccng1, as well as miR-192, miR-193a and miR-125b and were most pronounced in female B6C3F1 mice. Body weight loss, observed at week 1, was followed by weight gain throughout the feeding studies. These findings bolster safety and efficacy concerns for OEP-NF, and argue strongly for implementation of pre-market toxicity studies within the dietary supplement industry.

Stability of and Factors Related to Medical Student Specialty Choice of Psychiatry.

OBJECTIVE: Targeted efforts are needed to increase the number of medical students choosing psychiatry, but little is known about when students decide on their specialty or what factors influence their choice. The authors examined the timing and stability of student career choice of psychiatry compared with other specialties and determined what pre- and intra-medical school factors were associated with choosing a career in psychiatry. METHOD: Using survey data from students who graduated from U.S. allopathic medical schools in 2013 and 2014 (N=29,713), the authors computed rates of psychiatry specialty choice at the beginning and end of medical school and assessed the stability of that choice. A multivariate-adjusted logistic regression and recursive partitioning were used to determine the association of 29 factors with psychiatry specialty choice. RESULTS: Choice of psychiatry increased from 1.6% at the start of medical school to 4.1% at graduation. The stability of psychiatry specialty choice from matriculation to graduation, at just over 50%, was greater than for any other specialty. However, almost 80% of future psychiatrists did not indicate an inclination toward the specialty at matriculation. A rating of "excellent" for the psychiatry clerkship (odds ratio=2.66), a major in psychology in college (odds ratio=2.58), and valuing work-life balance (odds ratio=2.25) were the factors most strongly associated with psychiatry career choice. CONCLUSIONS: Students who enter medical school planning to become psychiatrists are likely to do so, but the vast majority of students who choose psychiatry do so during medical school. Increasing the percentage of medical students with undergraduate psychology majors and providing an exemplary psychiatry clerkship are modifiable factors that may increase the rate of psychiatry specialty choice.