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This study determined the relationship between physical activity (PA), circulating lipids throughout pregnancy and infant anthropometric outcomes at birth and 2 weeks of age.Women (N = 234) with normal weight (NW, BMI 18.5-24.9 kg/mWomen 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.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.

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

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. 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. 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. In conclusion, BF, MF, and SF support adequate growth and development up to age 6 years.

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.

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.

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.

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 non-survivors (n=30) of acetaminophen (APAP)-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 ALT was lower on day 1 than day 3, indicating a time point before the peak of injury (n=10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1,682 quantifiable proteins, 79 were elevated ≥4-fold in ALF patients vs. controls and 23 of those were further elevated ≥4-fold in non-survivors vs. survivors, indicating potential to predict death. Interestingly, the biomarker with best performance was LDH. To confirm the prognostic potential of LDH, we measured activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the non-survivors vs. survivors on both days. In addition, receiver operating characteristic (ROC) curve analyses revealed that LDH alone performed similarly to the model for end-stage liver disease (MELD), while a combination of MELD and LDH outperformed either alone. Finally, Upstream Analysis of our proteomics data indicated activation of LKB1-AMPK signaling in liver regeneration after APAP overdose and we confirmed that in mice. Overall, we conclude LDH can predict death in APAP-induced ALF and that LKB1-AMPK signaling may be a promising therapeutic target to improve survival.

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. 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. There was a strong correlation between the health utility scores of the two preference-weighted instruments (ρ = 0.6172, p

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.

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.

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.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.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.In conclusion, BF, MF, and SF support adequate growth and development up to age 6 years.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.

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. 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). 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. 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.

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&ndash, 40 years). Thus, we evaluated protein intake in healthy women [n = 182, mean &plusmn, SD, body mass index (BMI): 26.2 &plusmn, 4.2 kg/m2] in early pregnancy (8.4 &plusmn, 1.6 weeks, EP), late pregnancy (30.1 &plusmn, 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&middot, kg&minus, 1&middot, day&minus, 1) did not associate with HOMA2-IR at 12mo (&beta, = 0.153, p = 0.429) or 24mo (&beta, = &minus, 0.349, p = 0.098). LP protein did not associate with HOMA2-IR at 12mo (&beta, = 0.023, p = 0.916) or 24mo (&beta, 0.442, p = 0.085). Finally, average protein did not associate with HOMA2-IR at 12mo (&beta, = 0.711, p = 0.05) or 24mo (&beta, 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.

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.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.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.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.

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 &plusmn, 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 &middot, kg-1 &middot, 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 (&beta, = 1.37, p = 0.002) and PP (&beta, = 4.44, p &lt, 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 (&beta, = 0.95, p = 0.08). Therefore, early pregnancy BMI may be a better predictor of insulin sensitivity than dietary protein intake in late pregnancy.

Heart rate variability is a physiological measure associated with autonomic nervous system activity. This study hypothesized that lower pre-deployment HRV would be associated with higher post-deployment post-traumatic stress disorder (PTSD) symptoms. Three-hundred-forty-three Army National Guard soldiers enrolled in the Warriors Achieving Resilience (WAR) study were analyzed. The primary outcome was PTSD symptom severity using the PTSD Checklist – Military version (PCL) measured at baseline, 3- and 12-month post-deployment. Heart rate variability predictor variables included: high frequency power (HF) and standard deviation of the normal cardiac inter-beat interval (SDNN). Generalized linear mixed models revealed that the pre-deployment PCL*ln(HF) interaction term was significant (p < 0.0001). Pre-deployment SDNN was not a significant predictor of post-deployment PCL. Covariates included age, pre-deployment PCL, race/ethnicity, marital status, tobacco use, childhood abuse, pre-deployment traumatic brain injury, and previous combat zone deployment. Pre-deployment heart rate variability predicts post-deployment PTSD symptoms in the context of higher pre-deployment PCL scores.

OBJECTIVES: Findings of an association between maternal dietary protein intake (1.1–1.7 g·kg(−1)·day(−1)) close to requirements for pregnant women throughout gestation (1.22–1.52 g·kg(−1)·day(−1)) and offspring insulin sensitivity are mixed, perhaps as a result of the small spread in protein intake and the large gap between measurements (∼9–40 years). Therefore, our objective was to evaluate the association between a wider spread of dietary protein intake during pregnancy and measurements of insulin sensitivity in the offspring in early life. METHODS: Healthy women (n = 182, mean ± SD; BMI: 26.2 ± 4.2 kg/m2) were recruited early in pregnancy (

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.

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.

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 B6C3F(1) 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 B6C3F(1) 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.

This study assessed clinical scenarios of continuing monoclonal antibody (mAb) treatment for (+)-methamphetamine (METH) addiction, and the implications of missing or discontinuing this therapy. We hypothesized that chronic anti-METH mAb7F9 (METH KD = 9 nM) treatment of rats could significantly decrease METH-induced behaviors; even with repeated METH challenges, use of METH doses in excess of mAb binding sites, and after discontinuing mAb treatment which results in a 10-fold reduction in mAb7F9 serum concentrations. Male Sprague Dawley rats (n=6/group) were treated with i.v. saline or a loading dose of mAb7F9 to achieve instant steady-state conditions followed by two weekly (141 mg/kg) doses ending on day 14. METH (0.56 mg/kg) was administered four hours and three days after each saline or mAb7F9 treatment, and on day 21. This produced locomotion and rearing behavior that lasted about 120 min in control rats. In mAb7F9 treated rats, METH-induced distance traveled was significantly reduced from 60–120 min (P

This lead candidate selection study compared two anti-(+)-methamphetamine (METH) monoclonal antibodies (mAb) to determine their ability to reduce METH-induced locomotor effects and redistribute METH and (+)-amphetamine (AMP) in a preclinical overdose model. Both mAbs have high affinity for METH, but mAb4G9 has moderate and mAb7F9 has low affinity for AMP. In the placebo-controlled behavioral experiment, the effects of each mAb on the locomotor response to a single 1 mg/kg intravenous (IV) METH dose were determined in rats. The doses of mAb binding sites were administered such that they equaled 1, 0.56, 0.32, and 0.1 times the molar equivalent (mol-eq) of METH in the body 30 min after the METH dose. METH disposition was determined in separate animals that similarly received either a 1 or 0.32 mol-eq dose of mAb binding sites 30 min after a 1 mg/kg METH dose. Total METH-induced distance traveled was significantly reduced in rats that received the highest three doses of each mAb compared with saline. The duration of METH effects was also significantly reduced by mAb7F9 at the highest dose. The disposition of METH was altered dose-dependently by both mAbs as shown in reductions of volume of distribution and total clearance, and increases in elimination half-life. These data indicate that both mAbs are effective at reducing METH-induced behavior and favorably altering METH disposition. Both were therefore suitable for further preclinical testing as potential human medications for treating METH use; however, due to results reported here and in later studies, mAb7F9 was selected for clinical development.

Cocaine dependence is a major public health problem that is associated with serious medical,1 psychiatric,2 and social3 problems. Despite these compelling factors, no robustly effective pharmacotherapy for cocaine dependence has been developed. Depressive symptoms are common among cocaine-dependent patients4 and have been associated with greater severity of cocaine dependence and impairment5 as well as poor treatment outcome.6 Although most well-controlled trials have had disappointing results with antidepressants in unselected cocaine-dependent patients,7 antidepressants have shown some efficacy in treating depressed subgroups of cocaine-dependent patients8,9 (for exception10). Dopaminergic11 and serotonergic12 deficits have been shown to occur after long-term cocaine administration, suggesting a neurobiological link to depression, because the dopaminergic system has also been implicated in depression.13 Consequently, administration of antidepressants that inhibit both dopamine and serotonin reuptake would theoretically modulate serotonergic and/or dopaminergic dysfunction associated with cocaine abuse and/or depression. In a recently published study, we were able to demonstrate that the selective serotonin reuptake inhibitor (SSRI) sertraline (SERT), which also blocks reuptake of dopamine,14 significantly delayed time to relapse in recently abstinent cocaine-dependent patients presenting with depressive symptoms.8 These findings suggest that SERT may have utility as a relapse prevention agent for cocaine dependence. Nevertheless, response to SERT was not complete, with 53.1% of SERT-treated participants versus 70.3% of placebo (PLA)-treated participants having relapsed.8 Thus, the purpose of this study was to determine whether the prior results with SERT alone can be not only replicated, but also enhanced, with the addition of another agent to augment SERT’s effects. More recent evidence suggests that gamma-aminobutyric acid (GABA) function is also an important factor to be considered both in depression15 and cocaine dependence.16 Moreover, ample evidence suggests that cocaine interacts with the GABA system.17 Augmenting the efficacy of antidepressants with GABAergic agents has also been examined for the treatment of depression.18 Thus, we examined the clinical efficacy of the SSRI SERT,19 augmented with a low dose of the GABAergic agent gabapentin (GBP) that promotes release of GABA.20 As in our recently published SERT study,8 a relapse paradigm was used such that participants abstained from cocaine while residing at a residential facility during initial study medication induction and reinstatement of cocaine use was determined during subsequent outpatient treatment.

OBJECTIVE: To determine whether the diastolic closing margin (DCM), defined as diastolic blood pressure minus critical closing pressure, is associated with the development of early severe intraventricular hemorrhage (IVH). STUDY DESIGN: A reanalysis of prospectively collected data was conducted. Premature infants (gestational age 23-31 weeks) receiving mechanical ventilation (n = 185) had ∼1-hour continuous recordings of umbilical arterial blood pressure, middle cerebral artery cerebral blood flow velocity, and PaCO2 during the first week of life. Models using multivariate generalized linear regression and purposeful selection were used to determine associations with severe IVH. RESULTS: Severe IVH (grades 3-4) was observed in 14.6% of the infants. Irrespective of the model used, Apgar score at 5 minutes and DCM were significantly associated with severe IVH. A clinically relevant 5-mm Hg increase in DCM was associated with a 1.83- to 1.89-fold increased odds of developing severe IVH. CONCLUSION: Elevated DCM was associated with severe IVH, consistent with previous animal data showing that IVH is associated with hyperperfusion. Measurement of DCM may be more useful than blood pressure in defining cerebral perfusion in premature infants.

Premature infants are at an increased risk of intraventricular hemorrhage (IVH). The roles of hypotension and hyperemia are still debated. Critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. When diastolic ABP is equal to CrCP, CBF occurs only during systole. The difference between diastolic ABP and CrCP is the diastolic closing margin (DCM). We hypothesized that a low DCM was associated with IVH. One hundred eighty-six premature infants, with a gestational age (GA) range of 23-33 weeks, were monitored with umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity for 1-h sessions over the first week of life. CrCP was calculated linearly and using an impedance model. A multivariate generalized linear regression model was used to determine associations with severe IVH (grades 3-4). An elevated DCM by either method was associated with IVH (p 0.0001 for the linear method; p 0.001 for the impedance model). Lower 5-min Apgar scores, elevated mean CBF velocity, and lower mean ABP were also associated with IVH (p 0.0001). Elevated DCM, not low DCM, was associated with severe IVH in this cohort.

Aims Whether the selective serotonin reuptake inhibitor sertraline at 200 mg/day delays relapse in recently abstinent cocaine dependent individuals

Developmental ethanol exposure in rats during postnatal days (PN) 4-6 is known to cause significant loss of the cerebellar Purkinje cells. It is not known what happens to the surviving neurons as they continue to develop. This study was designed to quantify the interactions between the olivary climbing fibers and the Purkinje cells when the cerebellar circuits have matured. Rat pups were treated with a daily dose of ethanol (4.5g/kg body weight) delivered by intragastric intubation on PN4, PN4-6, or PN7-9. The interactions between the climbing fibers and the Purkinje cells were examined on PN40 using confocal microscopy. Mid-vermal cerebellar sections were stained with antibodies to calbindin-D28k (to visualize Purkinje cells) and vesicular glutamate transporter 2 (VGluT2, to visualize climbing fibers). Confocal z-stack images were obtained from Lobule 1 and analyzed with Imaris software to quantify the staining of the two antibodies. The VGluT2 immunostaining was significantly reduced and this was associated with alterations in the synaptic integrity, and synaptic number per Purkinje cell with only a single exposure on PN4 enough to cause the alterations. Previously, we demonstrated similar deficits in climbing fiber innervation when analyzed on PN14 (Pierce, Hayar, Williams, and Light, 2010). The present study confirms that these alterations are sustained and further identifies the decreased synaptic density as well as alterations to the general morphology of the molecular layer of the cerebellar cortex that are the result of the binge ethanol exposure.

Objective: The aim of this prospective observational trial was to generate reference values of middle cerebral artery cerebral blood flow velocity (CBFv) in normotensive, ventilated newborn survivors born at 23–24 weeks’ gestation during the first week (with normal cranial ultrasounds during the hospitalization), and to analyze how reference values may be affected by PCO2. Methods: Baseline systolic, diastolic, and mean CBFv were determined for 12 infants born at 23–24 weeks’ gestation (birth weight 643± 68 g) using transcranial Doppler ultrasound during several monitoring sessions during the first week, prior to intensive care procedures. Mean and 95% CI reference curves were generated using a locally weighted regression technique. Results: Mean CBFv increased from ∼10 to 21 cm/sec, and when baseline PCO2 was adjusted to 40, 50, and 60 mmHg, increased from ∼8.5 to 9, ∼12.5 to 16, and ∼16.5 to 23 cm/sec during the first week, respectively. Conclusion: Reference curves for middle cerebral artery CBFv for normotensive ventilated newborns born at 23–24 weeks’ gestation (with normal cranial ultrasounds) are presented for the first time. Since PCO2 is a potent regulator of CBF, when reporting cerebral hemodynamic values in the future, investigators must also report PCO2.

Most faith-based obesity intervention research has been conducted in African-American Protestant churches. However, Catholic communities might also benefit from a faith-tailored approach. Overweight Catholic individuals ( n = 34, 71% female) were randomized to a Catholic-tailored or standard behavioral 16-week group weight control program. Both conditions experienced significant weight losses (Catholic-tailored: -8.1 + 4.1%, Standard: -7.9 + 4.2%); however, treatment satisfaction was significantly greater in the Catholic-tailored program. The Catholic-tailored program experienced trends for greater attendance, more completed self-monitoring journals, and smaller weight regain six months post-treatment than the standard program. Catholic-tailored programs may represent a feasible, culturally acceptable and effective approach to weight loss/maintenance in this faith community.

PC-IDMS experiments for two peptides, laminin nonapeptide and the N-terminal tryptic peptide of prostate specific antigen, were performed utilizing a variety of alkylating reagents. These experiments were conducted to investigate how hydrophobicity influences the limits-of-detection (LOD) by altering their electrospray ionization response. Nonpolar surface areas were calculated for both peptides and all alkylating reagents to provide an estimate of the hydrophobicity of the differently alkylated peptides. Decreases in LOD by 2-fold were observed for both peptides between the best and worst performing combination of alkylating reagent. However, while an increase in hydrophobicity was found to aid in decreasing LOD to an extent, beyond a certain hydrophobicity, we observed a decrease.

A method employing protein cleavage isotope dilution mass spectrometry (PC-IDMS) was developed for quantification of C-reactive protein (CRP) in human plasma. This method was completed without the use of immunoaffinity chromatography or size exclusion chromatography, as previous mass spectrometric methods for the quantification of CRP have employed. A total of 110 human plasma samples were analyzed with PC-IDMS via 1-D nanoLC-MS/MS using a 30 min gradient with a triple quadrupole mass spectrometer operated in selective reaction monitoring (SRM) mode. The results from this newly developed method were compared to results generated from an enzyme-linked immunosorbent assay (ELISA) performed by an independent CLIA certified laboratory. The comparison of these results generated an R(2) = 0.9708 which indicates successful quantification of CRP from human plasma utilizing the methodology described herein. Interestingly, the PC-IDMS method provided concentration values that were approximately 10x the concentration reported by the ELISA method, which demonstrated that the method of detection is an important consideration when determining reference ranges of a particular analyte. In addition, data is shown that illustrates that, as epithelial ovarian cancer (EOC) progresses from stage I to stage IV, mean levels of CRP increase.

Objective: This observational study assessed the influence of family support and substance abuse on patterns of service use by individuals with schizophrenia. Methods: Polychotomous logistic regression was used to analyze an existing database for 258 individuals with schizophrenia who were between the ages of 18 and 67 and were recruited from public mental health care settings. Analyses determined the extent to which two consumer-identified factors, family support and substance abuse status, influenced patterns of outpatient service use (regular, irregular, and infrequent) for schizophrenia. Results: After the analysis adjusted for insight into illness, cognitive functioning, rural or urban residence, and gender, comorbid substance abuse and the interaction between substance abuse status and family support were significantly associated with patterns of service use. Comorbid substance abuse predicted irregular or infrequent patterns of service use over time. Stratified analyses indicated that weekly family support substantially reduced the adverse impact of substance abuse status on consumers’ patterns of service use, especially for those living in rural areas. Conclusions: This study provides evidence that ongoing family support is associated with substantial reductions in the adverse impact of substance abuse on consumers’ patterns of service use, especially for consumers living in rural areas. If confirmed in other populations, study findings suggest that reinforcing services and support for family members who provide informal care helps to sustain involvement in care by the especially vulnerable population of individuals with a dual diagnosis of schizophrenia and substance abuse. (Psychiatric Services 59:902–908, 2008)

Premature infants are at an increased risk of intraventricular hemorrhage (IVH). The roles of hypotension and hyperemia are still debated. Critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. When diastolic ABP is equal to CrCP, CBF occurs only during systole. The difference between diastolic ABP and CrCP is the diastolic closing margin (DCM). We hypothesized that a low DCM was associated with IVH. One hundred eighty-six premature infants, with a gestational age (GA) range of 23-33 weeks, were monitored with umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity for 1-h sessions over the first week of life. CrCP was calculated linearly and using an impedance model. A multivariate generalized linear regression model was used to determine associations with severe IVH (grades 3-4). An elevated DCM by either method was associated with IVH (p

BACKGROUND Indicators of program quality in graduate medical education have not been thoroughly well developed or studied. This study explores resident physicians' perceptions of program quality and associations with an external quality indicator. METHOD Responses to two open-ended questions about program strengths and areas in need of improvement were analyzed for 392 residents from 14 specialty programs that were reaccredited between 1999 and 2005. Computerized text analysis facilitated reliable categorization of 1,502 comments. Mann-Whitney U tests and nonparametric analyses for correlated data were used to examine associations between resident perceptions and accreditation length. RESULTS The most frequently mentioned program strengths were related to the quality of faculty, exposure to patients, education, and the social environment. Of these core strengths, residents in programs with longer cycle lengths had significantly more comments about the quality of faculty in their program. CONCLUSIONS Resident feedback can provide beneficial information about dimensions of program quality and the learning environment.

Cost-utility analyses using formulas to convert depression-free days (DFDs) to utility-weighted scores are increasingly common. These formulas are based on linear extrapolation of data documenting the correlation between depression symptom severity and generic health-related quality of life.We sought to examine the validity of formulas converting DFDs to utility weights.We undertook an observational study with data collection at baseline, 1 week and 1, 3, 6, 9, and 12 months on 77 subjects (42 inpatient, 35 outpatient) diagnosed with current major depression. Subjects were divided into treatment response categories based on changes in depression severity. Depression severity measures used were the Hamilton Rating Scale for Depression (HAM-17) and Beck Depression Inventory (BDI) and the health-related quality of life measure was the self-administered Quality of Well-Being scale (QWB-SA). DFD calculations were based on depression severity scores and converted to utility weights using available formulas. Utility-weighted data collected over the course of 1 year were used to estimate quality-adjusted life years (QALYs).QALYs estimated from the QWB-SA were significantly lower than those based on utility-weighted DFD calculations but the incremental QALYs were not significantly different. Using a slightly lower utility-weighted conversion factor for the BDI or a larger BDI severity range to calculate DFDs resulted in a better fit compared with the QWB-SA.Our results support the validity of the existing HAM-17 utility-weighted formula and suggest modifications for the BDI formula. If generic health-related quality of life measures are not available for conducting cost-utility analyses of depression interventions then the existing HAM-17 and modified BDI formulas appear to be reasonable alternatives.

The purpose of these studies was to determine if a high-affinity, anti-(+)-methamphetamine (METH) monoclonal antibody (mAb6H4; KD=11 nM) protects against METH-induced central nervous and cardiovascular system effects in rats. Rats (n=5 per group) received one of three anti-METH mAb6H4 doses, equal to 0.32, 0.56 or 1 times the mole equivalent (mol-eq) amount of METH in the body following a 1 mg/kg i.v. METH dose. Each rat was challenged with METH (1 mg/kg, i.v.) 1 and 4 days after the anti-METH mAb dose. The 1 mol-eq anti-METH mAb dose significantly reduced the duration of METH-induced locomotor activity (horizontal locomotion and rearing events), heart rate and blood pressure effects from 2 to 3 h to about an hour. This resulted in a significant reduction in total locomotor activity and the area under the hemodynamic effect vs. time curve for heart rate and blood pressure. In addition, the time to peak locomotor activity was decreased after the 1 mol-eq mAb dose vs. the lower doses. These changes were limited to the first METH challenge. The responses to the second METH challenge were not different from baseline. The peak hemodynamic and locomotor activity values were unchanged after both challenges. These results indicate anti-METH mAb6H4 can safely reduce the hemodynamic and locomotor effects of METH given one day after anti-METH IgG, and that the mAb is safe when administered in the absence of METH. These results are important because they indicate these antibody medications have simultaneous beneficial effects in multiple organ systems.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may underlie many herb-drug interactions. Serial serum concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with milk thistle or black cohosh modified P-gp activity in vivo. Sixteen healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg daily) or black cohosh (40 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxicaps, 0.4 mg) was administered orally before and at the end of each supplementation and control period. Serial digoxin serum concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the serum concentration time curves from 0 to 3 h (AUC(0-3)), AUC(0-24), Cmax, apparent oral clearance of digoxin (CL/F), and elimination half-life were used to assess the effects of milk thistle, black cohosh, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC(0-3), AUC(0-24), and Cmax, whereas clarithromycin increased these parameters significantly (p < 0.01). Significant changes in digoxin half-life and CL/F were also observed with clarithromycin. No statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either milk thistle or black cohosh, although digoxin AUC(0-3) and AUC(0-24) approached significance (p = 0.06) following milk thistle administration. When compared with rifampin and clarithromycin, supplementation with these specific formulations of milk thistle or black cohosh did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.

Objectives Phytochemical-mediated modulation of cytochrome P-450 activity may underlie many herb-drug interactions. Single time-point, phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal (Hydrastis canadensis), black cohosh (Cimicifuga racemosa), kava kava (Piper methysticum), or valerian (Valeriana officinalis) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity.

Elderly patients are more likely to ingest prescription medications concurrently with botanical supplements, and may therefore be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. In this study, single timepoint, phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly subjects.Twelve healthy volunteers between the ages of 60 and 76 years (mean age 67 years) were randomly assigned to receive each botanical supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and debrisoquine urinary recovery ratios (8-hour), respectively. The content of purported 'active' phytochemicals was determined for each supplement.Comparisons of pre- and post-St John's wort phenotypic ratios revealed significant induction of CYP3A4 (approximately 140%) and CYP2E1 activity (approximately 28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity.Elderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John's wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared with earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly.

Objectives Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of Citrus aurantium, Echinacea purpurea, milk thistle (Silybum marianum), or saw palmetto (Serenoa repens) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Methods Twelve healthy volunteers (6 women, 6 men) were randomly assigned to receive C aurantium, E purpurea, milk thistle, or saw palmetto for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported “active” phytochemicals was determined for each supplement. Results Comparisons of presupplementation and postsupplementation phenotypic ratios suggested that these particular supplements had no significant effect on CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Phytochemical profiles indicated that C aurantium was devoid of the CYP3A4 inhibitor 6′,7′-dihydroxybergamottin. Quantities of fatty acids, flavonolignans, and cichoric acid were consistent with label claims for saw palmetto, milk thistle, and E purpurea, respectively. Conclusions Botanical supplements containing C aurantium, milk thistle, or saw palmetto extracts appear to pose a minimal risk for CYP-mediated herb-drug interactions in humans. Although the effects of E purpurea on CYP activity were minor, further study into the interaction potential of this botanical is merited. Clinical Pharmacology & Therapeutics (2004) 76, 428–440; doi: 10.1016/j.clpt.2004.07.007

The P13 mid-latency auditory evoked potential in Rat is a sleep state-dependent response thought to be equivalent to the human P50 potential, a measure of the output of the reticular activating system. The amplitude of these potentials can be considered a measure of level of arousal, while, using a paired stimulus paradigm, the degree of habituation of the responses also can be assessed. Different durations of rotation were found to reduce the amplitude of the P13 potential, which recovered in a duration-dependent manner. Different durations of rotation led to decreases in habituation of the P13 potential again in a duration-dependent manner. These results suggest that rotation may affect the level of arousal as well as habituation to repetitive sensory inputs. Such effects could be interpreted to imply the presence, following rotation of sufficient duration, of a deficit in sensory gating, or distractibility, and are relevant for the study of the effects of space motion sickness.

Sleep problems in children with autism spectrum disorders (ASD) are under-recognized and under-treated. Identifying treatment value accounting for health effects on family members (spillovers) could improve the perceived cost-effectiveness of interventions to improve child sleep habits. A prospective cohort study (N = 224) was conducted with registry and postal survey data completed by the primary caregiver. We calculated quality of life outcomes for the child and the primary caregiver associated with treatments to improve sleep in the child based on prior clinical trials. Predicted treatment effects for melatonin and behavioral interventions were similar in magnitude for the child and for the caregiver. Accounting for caregiver spillover effects associated with treatments for the child with ASD increases treatment benefits and improves cost-effectiveness profiles.

The aim of this study was to determine whether massage therapy can be used as an adjunct intervention to induce sleep in infants born preterm.Thirty infants born at a minimum of 28 weeks gestational age, who were at the time of the study between 32 and 48 weeks adjusted gestational age, were randomly assigned to receive massage therapy on 1 day and not receive massage on an alternate day. The Motionlogger Micro Sleep Watch Actigraph recorded lower extremity activity on the morning of each day.No significant difference was found between groups for sleep efficiency (P = .13) during the time period evaluated. Groups differed significantly during the time period after the massage ended with more infants sleeping on the nonmassage day (χ = 4.9802, P = .026).Massage is well tolerated in infants born preterm and infants do not fall asleep faster after massage than without massage.

The role that homocysteine may play in post-carotid endarterectomy (CEA) restenosis due to intimal hyperplasia is not well understood. This study was designed to investigate the effects of different levels of dietary homocystine on: (1) plasma homocysteine; (2) post-CEA intimal hyperplasia; and (3) levels of the methyl donor S-adenosylmethionine (SAM) and its counterpart S-adenosylhomocysteine (SAH) in the homocysteine pathway.Male rats were fed specialized diets for 2 weeks pre- and post-CEA. Groups included control (0 homocystine added, n=9), 1.5 (1.5 g/kg homocystine added, n=10), 3.0 (3.0 g/kg homocystine added, n=9), and 4.5 (4.5 g/kg homocystine added, n=11). The rats underwent a surgical carotid endarterectomy. Endpoints included; plasma homocysteine, intimal hyperplasia, replicative index using with alpha-SM actin and BrdU, hepatic SAM levels, SAH levels, and the hepatic activities of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS).Increasing dietary homocystine produced a proportionate increase in plasma homocysteine and an increase in intimal hyperplasia. Regression analysis of plasma homocysteine levels and intimal hyperplasia showed a significant correlation (r=0.71,P=0.003). Plasma homocysteine levels above 15 microM were associated with significant increases in intimal hyperplasia above 6.5% (P=0.04). Elevation of plasma homocysteine levels to moderate levels (5-25 microM) resulted in significant post-CEA intimal hyperplasia. Cellular analysis of the area of intimal hyperplasia in all diet groups showed comparable amounts of cells positive for alpha-SM actin. However, with increasing levels of dietary homocystine and plasma homocysteine there was an increase in replicative index (P0.001) as determined by BrdU staining. Increasing dietary homocystine increased plasma homocysteine and was followed by increases in the replicative index thus producing increased intimal hyperplasia and lumenal stenosis. In hepatic measurements the 1.5 and 3.0 g/kg homocystine diets caused: increased liver activity of MTHFR (P=0.03) and decreased hepatic levels of SAM, SAH and SAM/SAH ratios compared to controls. Homocystine treatment did not cause significant alterations in CBS levels (P=0.992). These studies also showed no correlation of the MTHFR and CBS enzymes with plasma homocysteine levels or intimal hyperplasia. However, hepatic levels of SAM showed significant negative correlations with plasma homocysteine (r=-0.58; P=0.006) and with BrdU percentages of cellular proliferation (r=-0.69; P=0.06).The degree of post-CEA intimal hyperplasia in a rat model is directly related to the plasma level of homocysteine. The hyperplastic effects of homocysteine may be mediated in part by a physiological insufficiency of methyl donors as shown by decreases in SAM. Thus, increasing levels of plasma homocysteine enhanced and accelerated the smooth muscle cell response after CEA which led to increased intimal hyperplasia and lumenal stenosis.