Equivalent servings of free-range reindeer promote greater net protein balance compared to commercial beef.

Wild game consumption has been associated with health benefits but the acute influence on human protein metabolism remains unknown. We compared feeding-induced responses of equivalent amounts of free-range reindeer (FR) and commercial beef (CB) on protein kinetics using stable isotope methodology. Seven participants (age: 40 ± 14 years; body mass index: 24 ± 3 kg/m2) completed two randomised studies, ingesting 2 oz of FR or CB. L-[ring 2H5]phenylalanine & L-[ring 2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during the basal period and following consumption of FR or CB. Feeding-induced changes in whole-body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via plasma sample isotope enrichment analysis by gas chromatography-mass spectrometry; plasma essential amino acid (EAA) concentrations were determined by liquid chromatography-electrospray ionisation-mass spectrometry. Plasma post-prandial EAA concentrations were higher with FR compared to CB (P < 0.05). The acute feeding-induced PS response was not different, but PB was reduced and contributed to a superior level of NB (P < 0.00001) in FR compared to CB. Our results demonstrate that FR may influence more favourable protein metabolism than CB. These data support potential health benefits of wild game onf whole-body protein.Abbreviations: BMI: body mass index; DIAAS: digestible indispensable amino acid score; CB: commercial beef; EAA: essential amino acids; FR: free-range reindeer; Ra: rate of appearance; UAF: University of Alaska Fairbanks; USDA: USA Department of Agriculture.

Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress.

The comorbidity between alcohol use disorder and post-traumatic stress disorder represents a serious health care burden with few effective treatment options. The current study was designed to evaluate the effect of an alpha 1 receptor antagonist (doxazosin) and a novel anticonvulsant (zonisamide) in a model of alcohol (ethanol) dependence and stress exposure. The main dependent variable was voluntary ethanol intake in mice that experienced chronic intermittent ethanol (CIE) exposure and forced swim stress (FSS) alone, and in combination. Adult male and female C57BL/6J mice had access to a single bottle of 15% (v/v) ethanol for 1-hr in the home cage, 3-hr into the dark phase of the light/dark cycle. Once stable ethanol intake was established (~4 weeks), mice were separated into four groups (CTL, CIE, FSS, CIE + FSS). Mice in the FSS condition received 10-min FSS exposure 4-hr prior to drinking sessions (remaining mice were not disturbed). During baseline and the first two test cycles, all mice received vehicle (saline) injections (IP) 30-min before ethanol access. As previously observed, FSS increased ethanol drinking in dependent (CIE-exposed) mice but not in nondependent control (CTL) mice. In the following test cycles mice were evaluated for ethanol intake after administration of doxazosin, zonisamide or their combination. Results indicated that the three doses of doxazosin evaluated significantly reduced voluntary ethanol intake in all mice. Zonisamide had a more modest effect and may require a more prolonged treatment regime. The combined administration of both compounds was not more effective than each drug alone. This study suggests that doxazosin is reliable at reducing voluntary ethanol intake in mice independently of their history of ethanol dependence and stress exposure.

Chronic Effects of Neurotrauma Consortium (CENC) multicentre study interim analysis: Differences between participants with positive versus negative mild TBI histories.

OBJECTIVES: Compare characteristics and outcomes of combat-exposed military personnel with positive versus negative mild traumatic brain injury (mTBI) histories. SETTING: Recruitment was from registration lists and ambulatory clinics at four veterans administration hospitals. PARTICIPANTS: Consented veterans and service members completing initial evaluation by September 2016 (n = 492). DESIGN: Observational with cross-sectional analyses. MAIN MEASURES: Multimodal assessments including structured interviews, record review, questionnaires, neuroendocrine labs and neurocognitive and sensorimotor performance. RESULTS: In unadjusted comparisons to those absent lifetime mTBI, the mTBI positive group (84%) had greater combat exposure, more potential concussive events, less social support and more comorbidities, including asthma, sleeping problems and post-traumatic stress disorder. They also fared worse on all sensory and pain symptom scores and self-reported functional and global outcomes. They had poorer scores on Wechsler Adult Intelligence Scale-IV coding (processing speed), TMT-B (visual-motor integration and executive function) and two posturography subtests, but were otherwise equal to TBI negative participants on neurocognitive and sensorimotor testing and neuroendocrine levels. CONCLUSIONS: Although differences in characteristics exist which were not adjusted for, participants with historical mTBI have greater symptomatology and life functioning difficulties compared with non-TBI. Performance measures were less dissimilar between groups. These findings will guide further research within this accruing cohort.

Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel.

Patients with advanced post-thrombotic syndrome (PTS) and chronic iliac vein obstruction suffer major physical limitations and impairment of health-related quality of life. Currently there is a lack of evidence-based treatment options for these patients. Early studies suggest that imaging-guided, catheter-based endovascular therapy can eliminate iliac vein obstruction and saphenous venous valvular reflux, resulting in reduced PTS severity; however, these observations have not been rigorously validated. A multidisciplinary expert panel meeting was convened to plan a multicenter randomized controlled clinical trial to evaluate endovascular therapy for the treatment of advanced PTS. This article summarizes the findings of the panel, and is expected to assist in developing a National Institutes of Health-sponsored clinical trial and other studies to improve the care of patients with advanced PTS.

Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants.

BACKGROUND: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. CONCLUSION: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial.

Bed rest promotes reductions in walking speed, functional parameters, and aerobic fitness in older, healthy adults.

CONTEXT: The exact relationship between the bed rest-induced loss of skeletal muscle and reductions in muscle strength and physical performance in the older individuals is still unclear. OBJECTIVE: We examined the effect of 10 days of bed rest on changes in regional body composition, muscle strength, and functional status, and the relationship between these variables in older individuals. DESIGN, PARTICIPANTS, AND INTERVENTION: Regional body composition was measured using dual energy x-ray absorptiometry. We also determined changes in leg strength and several indices of functional status, including walking speed. RESULTS: Body weight, body mass index, and total and lower extremity lean mass decreased with bed rest. There were also significant reductions in knee extension one repetition maximum, isometric knee extension, knee extension 60° concentric, stair ascent time, stair ascent power, stair descent time, VO2 max, floor transfer test, 5-minute walk time, and chair stand. The overall change in total and lower extremity lean mass was also directly related to bed rest-induced reductions in one repetition maximum knee extension. CONCLUSIONS: Bed rest promoted overall declines in muscle mass, muscle strength, and physical function in older individuals. The changes in lean tissue were closely correlated with the bed rest-induced decline of muscle strength.

The VA/DoD Chronic Effects of Neurotrauma Consortium: An Overview at Year 1.

This federally funded program identifies gaps in research and provides support services for scientific, clinical, and translational research projects focused on the long-term effects of mild traumatic brain injury in veterans and active-duty service members.

Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

CONTEXT: Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population. OBJECTIVE: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m(2)) individuals. METHODS: We utilized a dual tracer technique (i.e., [6,6-(2)H2] glucose primed constant infusion and 1-[(13)C] glucose oral ingestion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios. RESULTS: Post-absorptive plasma glucose and insulin concentrations were not different between the three trials. Similarly, the response of glucose and insulin concentrations during the oral glucose tolerance tests (OGTT) was similar in the three trials. The results of the Matsuda index (ISI/M) were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2 ± 0.1, 1.1 ± 0.1, 1.3 ± 0.1 mg•kg(-1)•min(-1)), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2 ± 0.1, 4.3 ± 0.2, and 4.5 ± 0.4 mg•kg(-1)•min(-1)), respectively. CONCLUSIONS: Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. However, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.

Bed rest worsens impairments in fat and glucose metabolism in older, overweight adults.

BACKGROUND: The effects of bed rest on the dysregulation of fatty acid and glucose metabolism have not been addressed in the older population. OBJECTIVE: We examined the effect of 10 days of bed rest on fatty acid kinetics and hepatic and peripheral insulin resistance in aging. METHODS: We utilized an octreotide, basal glucagon replacement, multistage insulin infusion, and the concomitant infusion of [6,6 (2)H2]glucose to derive insulin-mediated suppression of glucose production and insulin-stimulated glucose disposal in nine older, overweight individuals (body mass index 28.1 ± 1.7 kg m(-2); 39.9% ± 1.9% fat). During the multistage insulin infusion, we also infused [1-(13)C]palmitate to examine free fatty acid rate of appearance (R(a)). RESULTS: Body weight, % body fat, and energy metabolism did not change with bed rest. There was a significant decrease (-2291 ± 316 cm(3)) in visceral fat, and no change in abdominal subcutaneous fat with bed rest. Insulin-mediated suppression of glucose production was modest prior to bed rest and was further reduced (>15% ± 2%) by bed rest. There was also a minor decrease in the insulin-mediated suppression of free fatty acid R(a) after bed rest and, as a consequence, a small variation in plasma free fatty acid from pre- to post-bed rest in the first stage of the multistage insulin infusion. There was also a significant bed rest-induced decline (>2.0 ± 0.6 mg kg FFM(-1) min(-1)) in insulin-stimulated glucose disposal. CONCLUSIONS: Preexisting impairments in insulin sensitivity are worsened by bed rest and seem linked to alterations in the regulation of free fatty acid in older, overweight individuals.

Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk.

BACKGROUND: Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia, and reduced severe retinopathy of prematurity in two randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed before efficacy trials. METHODS: Infants born in 23-29 wk of gestation were randomized to a single intravenous (i.v.) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed-effects approach. Safety outcomes were recorded. RESULTS: A single-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age strata, and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance was 0.0679 l/kg/h, endogenous production was 2.67 mg/kg/h, and the half-life was 5.22 h when modeled without the covariates. During the first 12 h, renal inositol excretion quadrupled in the 120 mg/kg group, returning to near-baseline value after 48 h. There was no diuretic side effect. No significant differences in adverse events occurred among the three groups (P > 0.05). CONCLUSION: A single-compartment model accounting for endogenous production satisfactorily described the PK of i.v. inositol.

Teaching kids to cope with anger: peer education.

Anger could be an early warning signal of violent behavior. Early peer education health promotion in relation to anger management could help children before uncontrolled anger becomes a problem in adolescence and adulthood. Peer education has been identified as a viable intervention strategy worldwide with various prevention programs for youth. The purpose of this article is to describe an anger management program (Teaching Kids to Cope with Anger, TKC-A 4th-8th graders) co-led by high school peer educators in an urban school district's summer school enhancement program. A program of five modules will be described. This paper discusses the peer educator implementation and recommendations for future implementation.

Estimating model-adjusted risks, risk differences, and risk ratios from complex survey data.

There is increasing interest in estimating and drawing inferences about risk or prevalence ratios and differences instead of odds ratios in the regression setting. Recent publications have shown how the GENMOD procedure in SAS (SAS Institute Inc., Cary, North Carolina) can be used to estimate these parameters in non-population-based studies. In this paper, the authors show how model-adjusted risks, risk differences, and risk ratio estimates can be obtained directly from logistic regression models in the complex sample survey setting to yield population-based inferences. Complex sample survey designs typically involve some combination of weighting, stratification, multistage sampling, clustering, and perhaps finite population adjustments. Point estimates of model-adjusted risks, risk differences, and risk ratios are obtained from average marginal predictions in the fitted logistic regression model. The model can contain both continuous and categorical covariates, as well as interaction terms. The authors use the SUDAAN software package (Research Triangle Institute, Research Triangle Park, North Carolina) to obtain point estimates, standard errors (via linearization or a replication method), confidence intervals, and P values for the parameters and contrasts of interest. Data from the 2006 National Health Interview Survey are used to illustrate these concepts.

EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly.

BACKGROUND & AIMS: Older individuals are more likely to experience extended hospitalization and become protein malnourished during hospitalization. The concomitant compulsory inactivity results in functional decline. Increasing protein intake in hospitalized patients improves nitrogen balance, but effects on function are unknown. In the present study, we examined the effects of increasing protein intake by essential amino acid (EAA) supplementation in older individuals subjected to 10 d bed rest on LBM and muscle function. METHODS: Subjects were given a placebo (n=12, 68+/-5 (SD) yrs, 83+/-19 kg) or 15 g of EAA (n=10, 71+/-6, 72+/-8 kg) 3 times per day throughout 10d of bed rest. LBM, muscle protein synthesis, and muscle function were determined before and after bed rest. Due to an imbalance in randomized gender distribution between groups, gender and beginning functional and LBM measures were utilized for analyses by repeated measures analysis of covariance (RMANCOVA). RESULTS: Analyses revealed the potential for the preservation of functional outcomes with EAA supplementation. CONCLUSIONS: Increasing protein intake above the RDA may preserve muscle function in the elderly during compulsory inactivity. EAA supplementation is potentially an efficient method of increasing protein intake without affecting satiety.

The impact of exercise training compared to caloric restriction on hepatic and peripheral insulin resistance in obesity.

CONTEXT: It has been difficult to distinguish the independent effects of caloric restriction versus exercise training on insulin resistance. OBJECTIVE: Utilizing metabolic feeding and supervised exercise training, we examined the influence of caloric restriction vs. exercise training with and without weight loss on hepatic and peripheral insulin resistance. DESIGN, PARTICIPANTS, AND INTERVENTION: Thirty-four obese, older subjects were randomized to: caloric restriction with weight loss (CR), exercise training with weight loss (EWL), exercise training without weight loss (EX), or controls. Based on an equivalent caloric deficit in EWL and CR, we induced matched weight loss. Subjects in the EX group received caloric compensation. Combined with [6,6(2)H(2)]glucose, an octreotide, glucagon, multistage insulin infusion was performed to determine suppression of glucose production (SGP) and insulin-stimulated glucose disposal (ISGD). Computed tomography scans were performed to assess changes in fat distribution. RESULTS: Body weight decreased similarly in EWL and CR, and did not change in EX and controls. The reduction in visceral fat was significantly greater in EWL (-71 +/- 15 cm(2)) compared to CR and EX. The increase in SGP was also almost 3-fold greater (27 +/- 2%) in EWL. EWL and CR promoted similar improvements in ISGD [+2.5 +/- 0.4 and 2.4 +/- 0.9 mg x kg fat-free mass (FFM)(-1) x min(-1)], respectively. CONCLUSIONS: EWL promoted the most significant reduction in visceral fat and the greatest improvement in SGP. Equivalent increases in ISGD were noted in EWL and CR, whereas EX provided a modest improvement. Based on our results, EWL promoted the optimal intervention-based changes in body fat distribution and systemic insulin resistance.

Influence of exercise intensity on abdominal fat and adiponectin in elderly adults.

To examine the influence of moderate-intensity (50% of VO(2peak)) exercise training (MI) versus high-intensity (75% of VO(2peak)) exercise training (HI) on regional fat distribution and plasma adiponectin, we randomized 18 overweight (body mass index [BMI] = 30 +/- 1 kg/m(2)) elderly (71 +/- 1 years) to HI, MI, or a control group (CON). Subjects enrolled in HI or MI completed a 12-week exercise training protocol designed to expend 1000 kcal/week. Body composition testing was completed prior to and following the exercise training using dual energy X-ray absorptiometry and a computed tomography scan. Plasma adiponectin was measured using enzymelinked immunoassay (ELISA). VO(2peak) improved in HI and MI, whereas there was no change in VO(2peak) in CON. No significant change in body weight, BMI, and % fat occurred in MI, HI, or CON. Although there was a significant reduction in visceral fat with HI (-39 cm(2)), there was no change in the MI or CON groups. In addition, there was a significant increase in thigh muscle attenuation in the HI group. There were no changes in thigh muscle attenuation in the MI and CON groups. Also, there was no change in plasma adiponectin in the MI, HI, or CON groups. In summary, our direct comparison of exercise intensity without weight loss promotes the efficacy of HI in the reduction in visceral fat, even without changes in adiponectin.

Visceral fat and adiponectin: associations with insulin resistance are tissue-specific in women.

Body fatness and its distribution are strongly and independently associated with peripheral insulin action. However, these associations are limited in their ability to predict the independent nature of hepatic and peripheral insulin resistance, especially in obese women. To define the relationships more precisely between regional fat distribution and adiponectin, and hepatic and peripheral insulin resistance, we studied 22 obese (43 +/- 0.1%) women who underwent a dual-energy X-ray absorptiometry scan and a computed tomography scan at the L4-L5 level. An octreotide (60 ng x kg(-1) x min(-1)), glucagon (0.65 ng x kg(-1) x min(-1)), and two-step insulin (0.25 mU x kg(-1) x min(-1) and 1.0 mU x kg(-1) x min(-1)) infusion was performed to quantify insulin-mediated suppression of hepatic glucose production (SGP) and insulin-stimulated glucose disposal (ISGD) in a simultaneous fashion. Hepatic glucose production (HGP) was measured using a primed, constant infusion of [6,6(2)H(2)] glucose. Mean plasma insulin increased from 5.6 +/- 0.1 microU/mL at baseline to 15.1 +/- 1.5 microU/mL in the first stage, and to 80.7 +/- 0.5 microU/mL in the second stage. Although there was no significant relationship between visceral adipose tissue (VAT) and basal HGP (r = 0.34, p = 0.117), there was a significant inverse correlation (r = -0.67, p = 0.003) between VAT and SGP. There was a significant correlation (r = 0.55, p = 0.008) between adiponectin and ISGD. In conclusion, these data support: (1) the inability of basal glucose metabolism to accurately reflect hepatic insulin resistance, (2) the deleterious role of VAT in the development of insulin resistance in the liver, and (3) provide additional support for the positive influence of adiponectin against peripheral insulin resistance in obese, postmenopausal women.

Modeling cholinesterase activity for human dietary risk assessment of carbamate insecticides.

This article demonstrates statistical models to quantify the interaction between a carbamate insecticide and acetylcholinesterase. Carbamates are a class of chemicals that inhibit the activity of acetylcholinesterase in humans, an enzyme involved in the regulation of the neurotransmitter acetylcholine. Following exposure to a carbamate insecticide, we specifically address (1) if acetylcholinesterase activity recovers to its level of preexposure activity; (2) the level of inhibition of acetylcholinesterase activity; (3) the recovery time of acetylcholinesterase activity to its preexposure level for a typical individual; and (4) the upper percentiles of the recovery time of acetylcholinesterase activity across individuals. A nonlinear mixed-effects model is fitted to data from a repeated measures experiment conducted with human volunteers randomly assigned to a control and four dose groups. Repeated measurements were taken prior to exposure and at 1, 2, 4, 6, 8, and 21 hours after exposure to the carbamate aldicarb. It was found that full recovery did occur. Inhibition at 1 hour was estimated with maximum inhibition most likely occurring prior to 1-hour postexposure. In addition, recovery was rapid even for sensitive individuals. Given this information, the potential effect from exposure to a carbamate consumed in the diet during a day can be quantitatively assessed.

The nonmedical use of prescription ADHD medications: results from a national Internet panel.

BACKGROUND: Emerging evidence suggests that nonmedical use (NMU) of prescription attention deficit/hyperactivity disorder (ADHD) medications is rising, but many previous investigations have used clinical or regionally based samples or limited their investigations to stimulants rather than to medications specifically used to treat ADHD. Using an Internet-based epidemiological survey, this paper advances understanding of the prevalence and correlates of NMU of medications used to treat ADHD, sources of diverted medications, motivations for use, and consumption patterns. METHODS: The study used a self-administered Internet survey of civilian, noninstitutionalized adults (N = 4,297) aged 18 to 49 in the United States. National-level estimates were created using propensity scoring methods and weighting procedures using data from three nationally representative probability surveys: a random-digit dialed telephone survey, the current U.S. Census, and the National Survey on Drug Use and Health (NSDUH). RESULTS: Past-year prevalence of NMU of ADHD medications was approximately 2%, with 4.3% reported among those aged 18 to 25 and 1.3% among those aged 26 to 49. Most respondents reporting NMU used on multiple occasions. Receipt of medications for ADHD was a significant correlate of past-year NMU, though most nonmedical users never had a prescription. Among persons who had never been prescribed medication to treat ADHD, friends or family members were the most common source. Productivity was the most frequently endorsed reason for NMU. Alcohol was the substance most commonly used in combination with ADHD drugs. CONCLUSION: Because most prescription ADHD medications currently are highly regulated, policy options for supply-side reduction of nonmedical use may include identifying those medications with lower abuse liability for inclusion on insurance formularies. Patient and physician education programs also may be useful tools to heighten awareness of intentional and unintentional diversion of ADHD medications for nonmedical purposes.