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Most patients are easily liberated from mechanical ventilation (MV) following resolution of respiratory failure and a successful trial of spontaneous breathing, but about 25% of patients experience difficult weaning. MV use leads to cellular changes and weakness, which has been linked to weaning difficulties and has been labeled ventilator induced diaphragm dysfunction (VIDD). Aggravating factors in human studies with prolonged weaning include malnutrition, chronic electrolyte abnormalities, hyperglycemia, excessive resistive and elastic loads, corticosteroids, muscle relaxant exposure, sepsis and compromised cardiac function. Numerous animal studies have investigated the effects of MV on diaphragm function. Virtually all these studies have concluded that MV use rapidly leads to VIDD and have identified cellular and molecular mechanisms of VIDD. Molecular and functional studies on the effects of MV on the human diaphragm have largely confirmed the animal results and identified potential treatment strategies. Only recently potential VIDD treatments have been tested in humans, including pharmacologic interventions and diaphragm "training". A limited number of human studies have found that specific diaphragm training can increase respiratory muscle strength in FTW patients and facilitate weaning, but larger, multicenter trials are needed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Metabolic myopathies are a diverse group of rare diseases in which impaired breakdown of stored energy leads to profound muscle dysfunction ranging from exercise intolerance to severe muscle wasting. Metabolic myopathies are largely caused by functional deficiency of a single gene and are generally subcategorized into three major types of metabolic disease: mitochondrial, lipid, or glycogen. Treatment varies greatly depending on the biochemical nature of the disease, and unfortunately no definitive treatments exist for metabolic myopathy. Since this group of diseases is inherited, gene therapy is being explored as an approach to personalized medical treatment. Adeno-associated virus-based vectors in particular have shown to be promising in the treatment of several forms of metabolic myopathy. This review will discuss the most recent advances in gene therapy efforts for the treatment of metabolic myopathies.

Pompe disease is due to mutations in the gene encoding the lysosomal enzyme acid α-glucosidase (GAA). Absence of functional GAA typically results in cardiorespiratory failure in the first year; reduced GAA activity is associated with progressive respiratory failure later in life. While skeletal muscle pathology contributes to respiratory insufficiency in Pompe disease, emerging evidence indicates that respiratory neuron dysfunction is also a significant part of dysfunction in motor units. Animal models show profound glycogen accumulation in spinal and medullary respiratory neurons and altered neural activity. Tissues from Pompe patients show central nervous system glycogen accumulation and motoneuron pathology. A neural mechanism raises considerations about the current clinical approach of enzyme replacement since the recombinant protein does not cross the blood-brain-barrier. Indeed, clinical data suggest that enzyme replacement therapy delays symptom progression, but many patients eventually require ventilatory assistance, especially during sleep. We propose that treatments which restore GAA activity to respiratory muscles, neurons and networks will be required to fully correct ventilatory insufficiency in Pompe disease., (Copyright © 2013. Published by Elsevier B.V.)

Objective: Face-to-face (FTF) weight management is costly and presents barriers for individuals seeking treatment; thus, alternate delivery systems are needed. The objective of this study was to compare weight management delivered by FTF clinic or group conference calls (phone)., Design and Methods: Randomized equivalency trial in 295 overweight/obese men/women (BMI = 35.1±4.9, Age = 43.8±10.2, Minority = 39.8%). Weight loss (0-6 months) was achieved by reducing energy intake between 1,200 and 1,500 kcal/day and progressing physical activity (PA) to 300 min/week. Weight maintenance (7-18 months) provided adequate energy to maintain weight and continued 300 min/week of PA. Behavioral weight management strategies were delivered weekly for 6 months and gradually reduced during 7-18 months. A cost analysis provided a comparison of expenses between groups., Results: Weight change from baseline to 6 months was -13.4 ± 6.7% and -12.3 ± 7.0% for FTF clinic and phone, respectively. Weight change from 6-18 months was 6.4 ± 7.0% and 6.4 ± 5.2%, for FTF clinic and phone, respectively. The cost to FTF participants was $789.58 more per person., Conclusions: Phone delivery provided equivalent weight loss and maintenance and reduced program cost. Ubiquitous access to phones provides a vast reach for this approach., (Copyright © 2013 The Obesity Society.)

Weight management for individuals with intellectual and developmental disabilities (IDD) has received limited attention. Studies on weight management in this population have been conducted over short time frames, in small samples with inadequate statistical power, infrequently used a randomized design, and have not evaluated the use of emerging effective dietary strategies such as pre-packaged meals (PMs). Low energy/fat PMs may be useful in individuals with IDD as they simplify meal planning, limit undesirable food choices, teach appropriate portion sizes, are convenient and easy to prepare, and when combined with fruits and vegetables provide a high volume, low energy dense meal. A randomized effectiveness trial will be conducted in 150 overweight/obese adults with mild to moderate IDD, and their study partners to compare weight loss (6 months) and weight maintenance (12 months) between 2 weight management approaches: 1. A Stop Light Diet enhanced with reduced energy/fat PMs (eSLD); and 2. A recommended care reduced energy/fat meal plan diet (RC). The primary aim is to compare weight loss (0-6 months) and weight maintenance (7-18 months) between the eSLD and RC diets. Secondarily, changes in chronic disease risk factors between the eSLD and RC diets including blood pressure, glucose, insulin, LDL-cholesterol, and HDL-cholesterol will be compared during both weight loss and weight maintenance. Finally, potential mediators of weight loss including energy intake, physical activity, data recording, adherence to the diet, study partner self-efficacy and daily stress related to dietary change will be explored., (© 2013. Published by Elsevier Inc. All rights reserved.)

Fluid milk consumed in conjunction with resistance training (RT) provides additional protein and calcium, which may enhance the effect of RT on body composition. However, the literature on this topic is inconsistent with limited data in adolescents. Therefore, we examined the effects of a supervised RT program (6 mo, 3 d/ wk, 7 exercises, 40-85% 1-repetition maximum) with daily milk supplementation (24 oz/day, one 16-oz dose immediately post-RT) on weight, fat mass (FM), and fat-free mass (FFM) assessed via dual-energy X-ray absorptiometry (baseline, 3 mo, 6 mo) in a sample of middle-school students who were randomly assigned to 1 of 3 supplement groups: milk, isocaloric carbohydrate (100% fruit juice), or water (control). Thirty-nine boys and 69 girls (mean age = 13.6 yr, mean BMI percentile = 85th) completed the study: milk n = 36, juice n = 34, water n = 38. The results showed no significant differences between groups for change in body weight (milk = 3.4 ± 3.7 kg, juice = 4.2 ± 3.1 kg, water = 2.3 ±2.9 kg), FM (milk = 1.1 ±2.8 kg, juice = 1.6 ± 2.5 kg, water = 0.4 ±3.6 kg), or FFM (milk = 2.2 ± 1.9 kg, juice = 2.7 ± 1.9 kg, water = 1.7 ± 2.9 kg) over 6 mo. FFM accounted for a high proportion of the increased weight (milk = 62%, juice = 64%, water = 74%). These results from a sample of predominantly overweight adolescents do not support the hypothesis that RT with milk supplementation enhances changes in body composition compared with RT alone.

Dorsalis pedis artery impingement is an extremely rare cause of foot claudication, with a single case reported in the literature. In this report, we describe the case of a 17-year-old female Irish dancer who presented with intermittent bilateral foot pain and discoloration during active plantar flexion., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Since limited data exist on adults with Prader-Willi syndrome (PWS) and growth hormone (GH) treatment, we report our experience on the effects of treatment for one year on body composition, physical activity, strength and energy expenditure, diet, general chemistry and endocrine data with quality of life measures., Design: We studied 11 adults with PWS (6F:5M; average age=32 yrs) over a 2 year period with GH treatment during the first year only. Electrolytes, IGF-I, glucose, thyroid, insulin, lipids, body composition, physical activity and strength, diet, energy expenditure and quality of life data were collected and analyzed statistically using linear modeling at baseline, at 12 months following GH therapy and at 24 months after treatment cessation for 12 months., Results: Total lean muscle mass was significantly increased (p<0.05) during GH treatment along with moderate-vigorous physical activity and plasma IGF-I and HDL levels, but returned to near baseline after treatment. Percent body fat decreased during the 12 months of GH treatment but increased after treatment., Conclusions: Previously reported beneficial effects of GH treatment in children with PWS were found in our adults regarding body composition, physical activity and plasma HDL and IGF-I levels. Several beneficial effects diminished to near baseline after cessation of GH treatment for 12 months supporting the continuation of treatment in PWS into adulthood and possibly adults not previously treated during childhood., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Pompe disease is an inherited neuromuscular disease caused by deficiency of lysosomal acid alpha-glucosidase (GAA) leading to glycogen accumulation in muscle and motoneurons. Cardiopulmonary failure in infancy leads to early mortality, and GAA enzyme replacement therapy (ERT) results in improved survival, reduction of cardiac hypertrophy, and developmental gains. However, many children have progressive ventilatory insufficiency and need additional support. Preclinical work shows that gene transfer restores phrenic neural activity and corrects ventilatory deficits. Here we present 180-day safety and ventilatory outcomes for five ventilator-dependent children in a phase I/II clinical trial of AAV-mediated GAA gene therapy (rAAV1-hGAA) following intradiaphragmatic delivery. We assessed whether rAAV1-hGAA results in acceptable safety outcomes and detectable functional changes, using general safety measures, immunological studies, and pulmonary functional testing. All subjects required chronic, full-time mechanical ventilation because of respiratory failure that was unresponsive to both ERT and preoperative muscle-conditioning exercises. After receiving a dose of either 1×10(12) vg (n=3) or 5×10(12) vg (n=2) of rAAV1-hGAA, the subjects' unassisted tidal volume was significantly larger (median [interquartile range] 28.8% increase [15.2-35.2], p<0.05). Further, most patients tolerated appreciably longer periods of unassisted breathing (425% increase [103-851], p=0.08). Gene transfer did not improve maximal inspiratory pressure. Expected levels of circulating antibodies and no T-cell-mediated immune responses to the vector (capsids) were observed. One subject demonstrated a slight increase in anti-GAA antibody that was not considered clinically significant. These results indicate that rAAV1-hGAA was safe and may lead to modest improvements in volitional ventilatory performance measures. Evaluation of the next five patients will determine whether earlier intervention can further enhance the functional benefit.

Isoxazoline insecticides have been shown to be potent blockers of insect GABA receptors with excellent activity on a broad pest range, including Lepidoptera and Hemiptera. Herein we report on the synthesis, biological activity and mode-of-action for a class of 4-heterocyclic aryl isoxazoline insecticides., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Compare weight loss and maintenance between a face-to-face (FTF) weight management clinic and a clinic delivered via virtual reality (VR)., Methods: Participants were randomized to 3 months of weight loss with a weekly clinic delivered via FTF or VR and then 6 months' weight maintenance delivered with VR. Data were collected at baseline and 3 and 6 months for weight and process variables. Twenty overweight and obese individuals (31.1 ± 3.6 years of age; body mass index, 32.8 ± 5.1; 85% females; 20% minorities) responded to advertisement and met inclusion criteria. Diets (1,200-1,800 kcal/d) used prepackaged meals, fruits and vegetables, and physical activity (300 min/wk)., Results: Weight loss was significantly greater for FTF at 10.8% compared with 7.6% for VR (P < .05). However, weight maintenance was significantly greater for VR at 14.0% compared with 9.5% for FTF (P < .05)., Conclusions and Implications: Virtual reality compares favorably with FTF for weight loss and may facilitate greater weight maintenance., (Copyright © 2013 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: Improving academic achievement and reducing the rates of obesity in elementary school students are both of considerable interest. Increased physical activity during academic instruction time during school offers a potential intervention to address both issues. A program titled "Physical Activity Across the Curriculum" (PAAC) was developed in which classroom teachers in 22 elementary schools were trained to deliver academic instruction using physical activity with a primary aim of preventing increased BMI. A secondary analysis of data assessed the impact of PAAC on academic achievement using the Weschler Individual Achievement Test-II and significant improvements were shown for reading, math and spelling in students who participated in PAAC. Based on the results from PAAC, an adequately powered trial will be conducted to assess differences in academic achievement between intervention and control schools called, "Academic Achievement and Physical Activity Across the Curriculum (A + PAAC).", Methods/design: Seventeen elementary schools were cluster randomized to A + PAAC or control for a 3-year trial. Classroom teachers were trained to deliver academic instruction through moderate-to-vigorous physical activity with a target of 100+ minutes of A + PAAC activities per week. The primary outcome measure is academic achievement measured by the Weschler Individual Achievement Test-III, which was administered at baseline (Fall 2011) and will be repeated in the spring of each year by assessors blinded to condition. Potential mediators of any association between A + PAAC and academic achievement will be examined on the same schedule and include changes in cognitive function, cardiovascular fitness, daily physical activity, BMI, and attention-to-task. An extensive process analysis will be conducted to document the fidelity of the intervention. School and student recruitment/randomization, teacher training, and baseline testing for A + PAAC have been completed. Nine schools were randomized to the intervention and 8 to control. A random sample of students in each school, stratified by gender and grade (A + PAAC = 370, Control = 317), was selected for outcome assessments from those who provided parental consent/child assent. Baseline data by intervention group are presented., Discussion: If successful, the A + PAAC approach could be easily and inexpensively scaled and disseminated across elementary schools to improve both educational quality and health., Funding Source: R01- DK85317., Trial Registration: US NIH Clinical Trials, http://NCT01699295.

In skeletal muscle, mitochondria exist as two subcellular populations known as subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS mitochondria preferentially respond to exercise training, suggesting divergent transcriptional control of the mitochondrial genomes. The transcriptional co-activator peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam) have been implicated in the direct regulation of the mitochondrial genome in mice, although SS and IMF differences may exist, and the potential signalling events regulating the mitochondrial content of these proteins have not been elucidated. Therefore, we examined the potential for PGC-1α and Tfam to translocate to SS and IMF mitochondria in human subjects, and performed experiments in rodents to identify signalling mechanisms regulating these translocation events. Acute exercise in humans and rats increased PGC-1α content in SS but not IMF mitochondria. Acute exposure to 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside in rats recapitulated the exercise effect of increased PGC-1α protein within SS mitochondria only, suggesting that AMP-activated protein kinase (AMPK) signalling is involved. In addition, rendering AMPK inactive (AMPK kinase dead mice) prevented exercise-induced PGC-1α translocation to SS mitochondria, further suggesting that AMPK plays an integral role in these translocation events. In contrast to the conserved PGC-1α translocation to SS mitochondria across species (humans, rats and mice), acute exercise only increased mitochondrial Tfam in rats. Nevertheless, in rat resting muscle PGC-1α and Tfam co-immunoprecipate with α-tubulin, suggesting a common cytosolic localization. These data suggest that exercise causes translocation of PGC-1α preferentially to SS mitochondria in an AMPK-dependent manner.

Unlabelled: Exercise is recommended by public health agencies for weight management; however, the role of exercise is generally considered secondary to energy restriction. Few studies exist that have verified completion of exercise, measured the energy expenditure of exercise, and prescribed exercise with equivalent energy expenditure across individuals and genders., Objective: The objective of this study was to evaluate aerobic exercise, without energy restriction, on weight loss in sedentary overweight and obese men and women., Design and Methods: This investigation was a randomized, controlled, efficacy trial in 141 overweight and obese participants (body mass index, 31.0 ± 4.6 kg/m(2) ; age 22.6 ± 3.9 years). Participants were randomized (2:2:1 ratio) to exercise at either 400 kcal/session or 600 kcal/session or to a nonexercise control. Exercise was supervised, 5 days/week, for 10 months. All participants were instructed to maintain usual ad libitum diets. Because of the efficacy design, completion of ≥90% of exercise sessions was an a priori definition of per protocol, and these participants were included in the analysis., Results: Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg (4.3%) and 5.2 ± 5.6 kg (5.7%), respectively, compared with weight gain for controls of 0.5 ± 3.5 kg (0.5%) (P < 0.05). Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant., Conclusions: Supervised exercise, with equivalent energy expenditure, results in clinically significant weight loss with no significant difference between men and women., (Copyright © 2012 The Obesity Society.)

Background and Purpose: Inspiratory muscle strength training (IMST) has been shown to improve maximal pressures and facilitate ventilator weaning in adults with prolonged mechanical ventilation (MV). The purposes of this case report are: (1) to describe the rationale for IMST in infants with MV dependence and (2) to summarize the device modifications used to administer training., Case Description: Two infants with congenital heart disease underwent corrective surgery and were referred for inspiratory muscle strength evaluation after repeated weaning failures. It was determined that IMST was indicated due to inspiratory muscle weakness and a rapid, shallow breathing pattern. In order to accommodate small tidal volumes of infants, 2 alternative training modes were devised. For infant 1, IMST consisted of 15-second inspiratory occlusions. Infant 2 received 10-breath sets of IMST through a modified positive end-expiratory pressure valve. Four daily IMST sets separated by 3 to 5 minutes of rest were administered 5 to 6 days per week. The infants' IMST tolerance was evaluated by vital signs and daily clinical reviews., Outcomes: Maximal inspiratory pressure (MIP) and rate of pressure development (dP/dt) were the primary outcome measures. Secondary outcome measures included the resting breathing pattern and MV weaning. There were no adverse events associated with IMST. Infants generated training pressures through the adapted devices, with improved MIP, dP/dt, and breathing pattern. Both infants weaned from MV to a high-flow nasal cannula, and neither required subsequent reintubation during their hospitalization., Discussion: This case report describes pediatric adaptations of an IMST technique used to improve muscle performance and facilitate weaning in adults. Training was well tolerated in 2 infants with postoperative weaning difficulty and inspiratory muscle dysfunction. Further systematic examination will be needed to determine whether IMST provides a significant performance or weaning benefit.

Objective: Weight gain is an important risk factor for gastroesophageal reflux disease (GERD); however, whether weight loss can lead to resolution of GERD symptoms is not clear. Our aim was to measure the impact of weight loss on GERD symptoms., Design and Methods: In a prospective cohort study at a tertiary referral center, overweight/obese subjects (BMI 25-39.9 kg/m2) were enrolled in a structured weight loss program. Weight loss strategies included dietary modifications, increased physical activity and behavioral changes. At baseline and at 6 months, BMI and waist circumference were measured and all participants completed a validated reflux disease questionnaire., Results: A total of 332 adult subjects, mean age 46 years and 66% women were prospectively enrolled. At baseline, the mean body weight, BMI, and waist circumference were 101 (±18) kg, 35 (±5) kg/m2 and 103 (±13) cm. At 6 months, majority of the subjects (97%) lost weight (average weight loss: 13 ± 7.7 kg) and as compared with baseline, there was a significant decrease in the overall prevalence of GERD (15 vs. 37%; P < 0.01) and the mean GERD symptom score (1.8 vs. 5.5; P < 0.01). Overall, 81% of the subjects had reduction in GERD symptom scores; 65% had complete resolution and 15% had partial resolution of reflux symptoms. There was a significant correlation between % body weight loss and reduction in GERD symptom scores (r = 0.17, P < 0.05)., Conclusions: In conclusion, the overall prevalence of GERD symptoms is high (37%) in overweight and obese subjects. A structured weight loss program can lead to complete resolution of GERD symptoms in the majority of these subjects., (Copyright © 2012 The Obesity Society.)

Published values regarding the sensitivity (IC(50)) of CPT-I (carnitine palmitoyltransferase I) to M-CoA (malonyl-CoA) inhibition in isolated mitochondria are inconsistent with predicted in vivo rates of fatty acid oxidation. Therefore we have re-examined M-CoA inhibition kinetics under various P-CoA (palmitoyl-CoA) concentrations in both isolated mitochondria and PMFs (permeabilized muscle fibres). PMFs have an 18-fold higher IC(50) (0.61 compared with 0.034 μM) in the presence of 25 μM P-CoA and a 13-fold higher IC(50) (6.3 compared with 0.49 μM) in the presence of 150 μM P-CoA compared with isolated mitochondria. M-CoA inhibition kinetics determined in PMFs predicts that CPT-I activity is inhibited by 33% in resting muscle compared with >95% in isolated mitochondria. Additionally, the ability of M-CoA to inhibit CPT-I appears to be dependent on P-CoA concentration, as the relative inhibitory capacity of M-CoA is decreased with increasing P-CoA concentrations. Altogether, the use of PMFs appears to provide an M-CoA IC(50) that better reflects the predicted in vivo rates of fatty acid oxidation. These findings also demonstrate that the ratio of [P-CoA]/[M-CoA] is critical for regulating CPT-I activity and may partially rectify the in vivo disconnect between M-CoA content and CPT-I flux within the context of exercise and Type 2 diabetes.

Carnitine palmitoyltransferase I has been viewed historically as the sole regulator of fatty acid oxidation. However, we have identified fatty acid translocase/CD36 as an additional control point. Specifically, fatty acid translocase/CD36 seems to have a novel dual mechanism of action with regard to fatty acid oxidation during exercise, influencing transport of lipids across the sarcolemmal membrane and into the mitochondria.

State-of-the-art treatment for weight management consists of a behavioral intervention to facilitate decreased energy intake and increased physical activity. These interventions are typically delivered face-to-face (FTF) by a health educator to a small group of participants. There are numerous barriers to participation in FTF clinics including availability, scheduling, the expense and time required to travel to the clinic site, and possible need for dependent care. Weight management clinics delivered by conference call have the potential to diminish or eliminate these barriers. The conference call approach may also reduce burden on providers, who could conduct clinic groups from almost any location without the expenses associated with maintaining FTF clinic space. A randomized trial will be conducted in 395 overweight/obese adults (BMI 25-39.9 kg/m(2)) to determine if weight loss (6 months) and weight maintenance (12 months) are equivalent between weight management interventions utilizing behavioral strategies and pre-packaged meals delivered by either a conference call or the traditional FTF approach. The primary outcome, body weight, will be assessed at baseline, 6, 12 and 18 months. Secondary outcomes including waist circumference, energy and macronutrient intake, and physical activity and will be assessed on the same schedule. In addition, a cost analysis and extensive process evaluation will be completed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

For ~40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (-21%) and oxidation (-25%), intramuscular lipids (less than or equal to -31%), and hepatic glycogen (-20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (-41%), oxidation (-37%), and exercise duration (-44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27-55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84-90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO.

The increased prevalence of obesity and the lack of treatment success both argue for the design and evaluation of strategies to prevent the development of overweight and obesity. To date, the role of resistance training (RT) in this regard is largely unexplored. RT may be effective for weight management as a result of increased fat-free mass (FFM), which may result in increased resting metabolic rate and increased physical activity energy expenditure. However, the literature relative to the efficacy of RT protocols recommended for healthy adults to alter the aforementioned parameters is inconsistent or inadequately evaluated. We will conduct a 9 month randomized controlled efficacy trial to compare changes in body composition (fat mass, FFM, % body fat) and energy balance in response to 2 volumes of RT (1 vs. 3 sets vs. non-exercise control) both at the completion of training (9 months) and 1 year later (body composition). This investigation will be conducted in a sample of healthy, normal and overweight, sedentary, young adult men and women; a group at high risk for development of overweight and obesity. Our results will provide information relative to the minimum volume of RT that may be associated with body weight/fat gain which may inform the development of guidelines for RT to prevent weight gain or to alter body composition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We evaluated weight loss response to 16 months of supervised exercise (45 min/day, 5 days/week, 75% heart-rate-reserve) in sedentary, overweight/obese participants without energy restriction in the Midwest Exercise Trial (MET1). Results indicated men lost weight, women did not. The gender differences were associated with differences in the energy expenditure of exercise (EEEx) (men=667±116; women=439±88 kcal/session) when exercise was prescribed by frequency, intensity and duration. MET2 is a randomized control trial designed and powered to examine differences in weight loss and gender in response to EEEx for men and women of 400 or 600 kcal/session, 5 days/week, for 10 months without energy restriction. One hundred forty-one participants will be randomized to 1 of 2 exercise groups or a non-exercise control. EEEx will be verified by indirect calorimetry monthly during the intervention. This study will evaluate: (1) the weight change response to two levels of EEEx versus non-exercise control; (2) gender differences in weight response to two levels of EEEx; (3) potential compensatory changes in energy intake and/or daily physical activity that may explain the observed weight changes. Results from this study may impact how exercise is prescribed for weight loss and prevention of weight regain and may clarify if men and women differ in response to exercise., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: This study evaluate the impact of a 6-month, 1-set RT protocol on changes in weight and body composition in overweight young adults., Methods: Sixty-three overweight young adults were randomized to RT or control; 55 participants (RT: N.=32; C: N.=23; BMI=27.3+2.9; age=20.7+2.7 yrs) competed the 6 month training protocol and all assessments. RT consisted of 1-set, 9 exercises, 3 times/wk., with a resistance of 3-6 repetition maximum (RM). Body composition was assessed using dual energy X-ray absorptiometry, and strength using 1RM. Participants were instructed to maintain their normal ad libitum diet and normal activities of daily living., Results: Body weight and BMI increased significantly (P<0.05) in RT and C, however; the between group difference was not significant. RT induced a mean increase in fat-free mass of 1.5 kg in both males and females with significant between groups differences for change in fat-free mass noted in the total sample, and in both males and females. Between group differences for change in fat mass were not statistically significant in the total sample, or in either gender. Significant between group differences for change in % fat were noted in the total sample (RT=-0.3%, C=+5.8%, P<0.05) and in females (RT=-3.7%, C=+3.0%, P<0.01), but not in males (RT=3.4%, C=9.8%). Significant between group differences (P<0.001) were observed for change in chest (RT=45 %, C=3%) and leg press (RT=57 %, C=9%) maximal strength., Conclusion: A 6 month, 1-set RT program in overweight young adults increased fat-free mass and prevented increases in fat mass and % fat.

Respiratory dysfunction due progressive weakness of the respiratory muscles, particularly the diaphragm, is a major cause of death in the neuromuscular disease (NMD) X-linked myotubular myopathy (XLMTM). Methods of respiratory assessment in patients are often difficult, especially in those who are mechanically ventilated. The naturally occuring XLMTM dog model exhibits a phenotype similar to that in patients and can be used to determine quantitative descriptions of dysfunction as clinical endpoints for treatment and the development of new therapies. In experiments using respiratory impedance plethysmography (RIP), XLMTM dogs challenged with the respiratory stimulant doxapram displayed significant changes indicative of diaphragmatic weakness., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although the prevalence of inspiratory muscle strength training has increased in clinical medicine, its effect on diaphragm fiber remodeling is not well-understood and no relevant animal respiratory muscle strength training-rehabilitation experimental models exist. We tested the postulate that intrinsic transient tracheal occlusion (ITTO) conditioning in conscious animals would provide a novel experimental model of respiratory muscle strength training, and used significant increases in diaphragmatic fiber cross-sectional area (CSA) as the primary outcome measure. We hypothesized that ITTO would increase costal diaphragm fiber CSA and further hypothesized a greater duration and magnitude of occlusions would amplify remodeling., Methodology/principal Findings: Sprague-Dawley rats underwent surgical placement of a tracheal cuff and were randomly assigned to receive daily either 10-minute sessions of ITTO, extended-duration, 20-minute ITTO (ITTO-20), partial obstruction with 50% of cuff inflation pressure (ITTO-PAR) or observation (SHAM) over two weeks. After the interventions, fiber morphology, myosin heavy chain composition and CSA were examined in the crural and ventral, medial, and dorsal costal regions. In the medial costal diaphragm, with ITTO, type IIx/b fibers were 26% larger in the medial costal diaphragm (p<0.01) and 24% larger in the crural diaphragm (p<0.05). No significant changes in fiber composition or morphology were detected. ITTO-20 sessions also yielded significant increases in medial costal fiber cross-sectional area, but the effects were not greater than those elicited by 10-minute sessions. On the other hand, ITTO-PAR resulted in partial airway obstruction and did not generate fiber hypertrophy., Conclusions/significance: The results suggest that the magnitude of the load was more influential in altering fiber cross-sectional area than extended-duration conditioning sessions. The results also indicated that ITTO was associated with type II fiber hypertrophy in the medial costal region of the diaphragm and may be an advantageous experimental model of clinical respiratory muscle strength training.

Objective: We examined the effects of cardiothoracic surgery, including cardiopulmonary bypass and controlled mechanical ventilation, on messenger RNA gene expression in human diaphragm. We hypothesized that genes responsible for stress response, redox regulation, protein turnover, energy metabolism, and contractile function would be altered by cardiothoracic surgery., Methods: Paired diaphragm biopsy samples were obtained from 5 male patients (67 ± 11 years) during cardiothoracic surgery, the first as soon as the diaphragm was exposed and the second as late in surgery as possible (4.9 ± 1.8 hours between samples). We profiled messenger RNA from 5 specimen pairs with microarray analysis (Hu U133 plus 2.0; Affymetrix UK Ltd, High Wycombe, UK). Quantitative reverse transcriptase polymerase chain reaction was performed with a select set of genes exhibiting differential expression for validation., Results: Microarray analysis identified 779 differentially expressed (early vs late samples) unique gene products (P < .005). Postoperatively, genes related to stress response and redox regulation were upregulated. Additionally, we found significantly upregulated expression of cathepsin C (2.7-fold), cathepsin L1 (2.0-fold), various ubiquitin-conjugating enzymes (E2, approximately 1.8-fold), proinflammatory cytokine interleukin 6 (15.6-fold), and muscle-specific ubiquitin ligase (MuRF-1, 2.6-fold). Comparison of fold change values obtained by quantitative reverse transcriptase polymerase chain reaction and microarray yielded significant correlation (r = 0.95, P < .0001)., Conclusions: Cardiothoracic surgery results in rapid changes in human diaphragm gene expression in the operating room, including genes related to stress response, inflammation, redox regulation, and proteolysis. These results may provide insight into diaphragm muscle biology after prolonged cardiothoracic procedures., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The soluble guanylate cyclase (sGC) activator Cinaciguat (BAY 58-2667) represents a novel class of drugs that selectively activate oxidised sGC. The extent of oxidised sGC depends on the patient's oxidative burden. We here describe two platelet-based assays that allow determining the extent of oxidised sGC and thus provide a basis for an individualised pharmacotherapy., Methods/results: Platelets obtained from patients with (n=12) and without (n=12) coronary artery disease (CAD) were examined by flow cytometry (P-selectin expression), and Western blots (vasodilator associated phosphoprotein, VASP-phosphorylation). Results were compared to maximal oxidation of sGC achieved by the oxidising agent ODQ (1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one). Treatment of platelets with Cinaciguat resulted in differential activation of oxidised sGC. Platelet P-selectin expression and VASP-phosphorylation revealed significant differences (p=0.012, p=0.039, respectively) between CAD and non-CAD patients., Conclusion: We describe platelet-based assays that allow the determination of patients' oxidative status and thus allow the prediction of pharmacological response to direct sGC activators., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Sorting procedures are frequently adopted as an alternative to dissimilarity ratings to measure the dissimilarity of large sets of stimuli in a comparatively short time. However, systematic empirical research on the consequences of this experiment-design choice is lacking. We carried out a behavioral experiment to assess the extent to which sorting procedures compare to dissimilarity ratings in terms of efficiency, reliability, and accuracy, and the extent to which data from different data-collection methods are redundant and are better fit by different distance models. Participants estimated the dissimilarity of either semantically charged environmental sounds or semantically neutral synthetic sounds. We considered free and hierarchical sorting and derived indications concerning the properties of constrained and truncated hierarchical sorting methods from hierarchical sorting data. Results show that the higher efficiency of sorting methods comes at a considerable cost in terms of data reliability and accuracy. This loss appears to be minimized with truncated hierarchical sorting methods that start from a relatively low number of groups of stimuli. Finally, variations in data-collection method differentially affect the fit of various distance models at the group-average and individual levels. On the basis of these results, we suggest adopting sorting as an alternative to dissimilarity-rating methods only when strictly necessary. We also suggest analyzing the raw behavioral dissimilarities, and avoiding modeling them with one single distance model.

FAT/CD36 (fatty acid translocase/Cluster of Differentiation 36), a plasma membrane fatty-acid transport protein, has been found on mitochondrial membranes; however, it remains unclear where FAT/CD36 resides on this organelle or its functional role within mitochondria. In the present study, we demonstrate, using several different approaches, that in skeletal muscle FAT/CD36 resides on the OMM (outer mitochondrial membrane). To determine the functional role of mitochondrial FAT/CD36 in this tissue, we determined oxygen consumption rates in permeabilized muscle fibres in WT (wild-type) and FAT/CD36-KO (knockout) mice using a variety of substrates. Despite comparable muscle mitochondrial content, as assessed by unaltered mtDNA (mitochondrial DNA), citrate synthase, β-hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase complex IV and respiratory capacities [maximal OXPHOS (oxidative phosphorylation) respiration] in WT and KO mice, palmitate-supported respiration was 34% lower in KO animals. In contrast, palmitoyl-CoA-supported respiration was unchanged. These results indicate that FAT/CD36 is key for palmitate-supported respiration. Therefore we propose a working model of mitochondrial fatty-acid transport, in which FAT/CD36 is positioned on the OMM, upstream of long-chain acyl-CoA synthetase, thereby contributing to the regulation of mitochondrial fatty-acid transport. We further support this model by providing evidence that FAT/CD36 is not located in mitochondrial contact sites, and therefore does not directly interact with carnitine palmitoyltransferase-I as original proposed.

Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disability. In early-onset severe cases, the natural history is characteristically cardiorespiratory failure and death in the first year of life. Since the advent of enzyme replacement therapy (ERT), the clinical outcomes have improved. However, it has become apparent that a new natural history is being defined in which some patients have substantial improvement following ERT, while others develop chronic disability reminiscent of the late-onset disease. In order to improve on the current clinical outcomes in Pompe patients with diminished clinical response to ERT, we sought to address the cause and potential for the treatment of disease manifestations which are not amenable to ERT. In this review, we will focus on the preclinical studies that are relevant to the development of a gene therapy strategy for Pompe disease, and have led to the first clinical trial of recombinant adeno-associated virus-mediated gene-based therapy for Pompe disease. We will cover the preliminary laboratory studies and rationale for a clinical trial, which is based on the treatment of the high rate of respiratory failure in the early-onset patients receiving ERT.

Of 79 overweight adults with intellectual or developmental disabilities who participated in a weight loss intervention, 73 completed the 6-month diet phase. The emphasis in the intervention was consumption of high volume, low calorie foods and beverages, including meal-replacement shakes. Lower calorie frozen entrees were recommended to control portion size. A walking activity was encouraged. Participants attended monthly meetings in which a small amount of cash was exchanged for self-recorded intake and exercise records completed on picture-based forms. Average weight loss was 13.2 pounds (6.3%) of baseline weight at 6 months, with weight loss shown by 64 of the 73 individuals enrolled. Those completing a 6-month follow-up phase showed weight loss of 9.4% of baseline. Increased choice and control are discussed as possible contributors to individual success.

Objective: To report the use of inspiratory muscle strength training to treat repeated ventilatory insufficiency in a child with nemaline myopathy who underwent cardiac and renal transplantation., Design: Case report., Setting: Pediatric intensive care unit of a tertiary care university teaching hospital., Patient: A 16-yr-old female with nemaline myopathy affecting cardiorespiratory function, recent organ transplantation, and delayed postoperative ventilatory recovery., Intervention: Inspiratory muscle strength training was provided 5 days weekly for 2 wks, accompanied by progressive weaning from noninvasive ventilation., Measurements and Main Results: Maximal inspiratory pressure increased from -36.7 cm H2O to -77.8 cm H2O, accompanied by improved inspiratory flow, volume, pressure activation and power. During the training period, the patient was weaned from continuous noninvasive ventilatory assist to her preoperative level of ventilatory function., Conclusion: Inspiratory muscle training may be a beneficial component of care for children with nemaline myopathy who experience acute ventilatory insufficiency.

Introduction: Most patients are readily liberated from mechanical ventilation (MV) support, however, 10% - 15% of patients experience failure to wean (FTW). FTW patients account for approximately 40% of all MV days and have significantly worse clinical outcomes. MV induced inspiratory muscle weakness has been implicated as a contributor to FTW and recent work has documented inspiratory muscle weakness in humans supported with MV., Methods: We conducted a single center, single-blind, randomized controlled trial to test whether inspiratory muscle strength training (IMST) would improve weaning outcome in FTW patients. Of 129 patients evaluated for participation, 69 were enrolled and studied. 35 subjects were randomly assigned to the IMST condition and 34 to the SHAM treatment. IMST was performed with a threshold inspiratory device, set at the highest pressure tolerated and progressed daily. SHAM training provided a constant, low inspiratory pressure load. Subjects completed 4 sets of 6-10 training breaths, 5 days per week. Subjects also performed progressively longer breathing trials daily per protocol. The weaning criterion was 72 consecutive hours without MV support. Subjects were blinded to group assignment, and were treated until weaned or 28 days., Results: Groups were comparable on demographic and clinical variables at baseline. The IMST and SHAM groups respectively received 41.9 ± 25.5 vs. 47.3 ± 33.0 days of MV support prior to starting intervention, P = 0.36. The IMST and SHAM groups participated in 9.7 ± 4.0 and 11.0 ± 4.8 training sessions, respectively, P = 0.09. The SHAM group's pre to post-training maximal inspiratory pressure (MIP) change was not significant (-43.5 ± 17.8 vs. -45.1 ± 19.5 cm H2O, P = 0.39), while the IMST group's MIP increased (-44.4 ± 18.4 vs. -54.1 ± 17.8 cm H2O, P < 0.0001). There were no adverse events observed during IMST or SHAM treatments. Twenty-five of 35 IMST subjects weaned (71%, 95% confidence interval (CI) = 55% to 84%), while 16 of 34 (47%, 95% CI = 31% to 63%) SHAM subjects weaned, P = .039. The number of patients needed to be treated for effect was 4 (95% CI = 2 to 80)., Conclusions: An IMST program can lead to increased MIP and improved weaning outcome in FTW patients compared to SHAM treatment., Trial Registration: ClinicalTrials.gov: NCT00419458.

A reduction in skeletal muscle fatty acid oxidation (FAO), manifested as a reduction in mitochondrial content and (or) FAO within mitochondria, may contribute to the development of insulin resistance. n-3 polyunsaturated fatty acids (PUFA) have been observed to increase the capacity for FAO and improve insulin sensitivity. We used the fat-1 mouse model, a transgenic animal capable of synthesizing n-3 PUFA from n-6 PUFA, to examine this relationship. Fat-1 mice exhibited a approximately 20-fold decrease in the n-6/n-3 ratio in skeletal muscle, and plasma glucose and the area under the glucose curve were significantly (p < 0.05) lower in fat-1 mice during a glucose challenge test. The improvement in whole-body glucose tolerance in the fat-1 mouse was associated with a approximately 21% (p < 0.05) decrease in whole-muscle citrate synthase (CS) activity (in red muscle only), without alterations in CS activity of isolated mitochondria (either red or white muscle; p > 0.05). These data suggest that the fat-1 mouse has decreased skeletal muscle mitochondrial content. However, the intrinsic ability of mitochondria to oxidize fatty acids was not altered in the fat-1 mouse, as rates of palmitate oxidation in isolated mitochondria from both red and white muscle were unchanged. Overall, this study demonstrates that a decrease in the n-6/n-3 ratio can enhance glucose tolerance in healthy animals, independent of changes in mitochondrial content.

Objectives: This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss., Methods: Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of approximately 2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (approximately 20%) or fat (approximately 30%) intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance., Results: Body weight change was not significantly different within or between groups during weight maintenance (p>0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p<0.05). Group*time interactions were significant for large and medium VLDL (p>0.05)., Conclusion: Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

Background: Diets high in either dairy or calcium during moderate weight reduction both prevent loss of bone mineral density (BMD) and suppress bone turnover. The purpose of this study was to determine whether recommended dairy and calcium intakes during weight maintenance favorably affect total body BMD (TBBMD) and bone mineral content (TBBMC) in obese adults., Methods: Obese men (n=49) and women (n=64), aged 40.8+/-0.6 years, underwent 12 weeks of moderate energy restriction (approximately 1200 kcal/day) followed by 24 weeks on either a low or recommended dairy weight maintenance diet. The TBBMC and TBBMD values were measured using dual energy X-ray absorptiometry at baseline, 12, 24 and 36 weeks. Concentrations of calcium, intact parathyroid hormone (iPTH), 25OH and 1,25 (OH)(2) vitamin D in plasma were also measured. Data were analyzed using a two-factor repeated measures analysis of variance., Results: After weight loss, women exhibited a small, but statistically significant, increase in TBBMC (1.17+/-0.57%), whereas TBBMD increased in the men (1.34+/-0.28%). The iPTH concentration decreased significantly in all subjects. Despite significantly greater intakes of calcium, vitamin D and protein compared with the recommended dairy diet, there were no treatment-related differences in outcome variables after 24 weeks of weight maintenance. The TBBMC remained unchanged in women during weight stabilization; both TBBMC and TBBMD decreased in men (-1.59+/-0.51% and -0.70+/-0.25%, respectively)., Conclusions: In summary, results of this study do not provide convincing evidence that moderate weight loss through energy restriction and mild exercise reduces TBBMC in obese men and women. Similarly, a weight-maintenance diet providing the recommended daily servings of dairy does not seem to affect changes in BMC after weight loss.

C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus castaneus, differ in nutrient intake behaviors, including dietary fat and carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are present between these strains on chromosome (Chr) 17. Here we report the refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST-( D17Mit19-D17Mit91 ) congenic mice described previously. This new subcongenic strain possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background. Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total calorie intake per body weight, while fat intake remains equivalent. Unexpectedly, this CAST genomic segment also confers two new physical activity phenotypes: 22% higher spontaneous physical activity levels and significantly increased voluntary wheel-running activity compared with the parental B6 strain. Overall, these data suggest that gene(s) involved in carbohydrate preference and increased physical activity are contained within the proximal region of Chr 17. Interval-specific microarray analysis in hypothalamus and skeletal muscle revealed differentially expressed genes within the subcongenic region, including neuropeptide W (Npw); glyoxalase I (Glo1); cytochrome P450, family 4, subfamily f, polypeptide 1 (Cyp4f15); phospholipase A2, group VII (Pla2g7); and phosphodiesterase 9a (Pde9a). This subcongenic strain offers a unique model for dissecting the contributions and possible interactions among genes controlling food intake and physical activity, key components of energy balance.

Objective: The primary purpose of this study was to examine the construct validity of a continuous metabolic syndrome score (cMetS) in children. The secondary purpose was to identify a cutpoint value(s) for an adverse cMetS based on receiver operating characteristic (ROC) curve analysis., Methods: 378 children aged 7 to 9 years were assessed for the metabolic syndrome which was determined by age-modified cutpoints. High-density-lipoprotein cholesterol, triglycerides, the homeostasis assessment model of insulin resistance, mean arterial pressure, and waist circumference were used to create a cMetS for each subject., Results: About half of the subjects did not possess any risk factors while about 5% possessed the metabolic syndrome. There was a graded relationship between the cMetS and the number of adverse risk factors. The cMetS was lowest in the group with no adverse risk factors (-1.59 +/- 1.76) and highest in those possessing the metabolic syndrome (> or =3 risk factors) (7.05 +/- 2.73). The cutoff level yielding the maximal sensitivity and specificity for predicting the presence of the metabolic syndrome was a cMetS of 3.72 (sensitivity = 100%, specificity = 93.9%, and the area of the curve = 0.978 (0.957-0.990, 95% confidence intervals)., Conclusion: The results demonstrate the construct validity for the cMetS in children. Since there are several drawbacks to identifying a single cut-point value for the cMetS based on this sample, we urge researchers to use the approach herein to validate and create a cMetS that is specific to their study population.

The association between trans-fatty acids (TFA) and cancer risk is poorly understood and remains controversial. It is recognised that unique biological effects are associated with specific isoforms within families of fatty acids such as those belonging to the n-3 fatty acids. Furthermore, the interactions between diet and genetic polymorphisms are increasingly recognised for their potential risk-modifying effects on human health and disease. Therefore, the aim of the present review is to evaluate whether specific TFA isomers and genetic polymorphisms differentially modify cancer risk in prostate, colon and breast cancers in animal and human models. Potential mechanisms of action by which TFA may affect cancer development are also reviewed. Overall, across a number of experimental models and human studies, there is insufficient and inconsistent evidence linking specific TFA isomers to cancers of the prostate, colon and breast. A number of methodological limitations and experimental considerations were identified which may explain the inconsistencies observed across these studies. Therefore, further research is warranted to accurately assess the relationship between TFA and cancer risk.

To determine whether a single-point triglyceride (TG) concentration could estimate the 8-hour postprandial lipemic (PPL) response, men and women performed baseline PPL (n=188) and postexercise PPL (n=92) trials. Correlations were generated between TG concentrations at baseline and at various time points after a high-fat meal vs 8-hour area under the TG curve (TG-AUC) and peak TG level. Stepwise multiple regression and bootstrap simulations using TG level and additional predictor variables of sex, age, percentage of body fat, training status, and maximal oxygen consumption indicated that the 4-hour TG concentrations accounted for >90% of the variance in TG-AUC and peak TG responses during the PPL trials. Equations were confirmed by cross-validation in healthy as well as at-risk individuals with components of the cardiometabolic syndrome. Our data suggest that the 4-hour TG value is highly related to the total 8-hour PPL response and can be used for accurate estimation of PPL in a clinical or research setting., (2009 Wiley Periodicals, Inc.)

Objective: Moderate weight loss alters bone turnover and reduces bone mineral density in overweight men and women. However, it is not known whether bone turnover is normalized during weight maintenance postweight loss. Thus, the objective of the present study was to examine changes in serum bone turnover markers during 9 months of weight maintenance following weight reduction on a very low-energy diet (VLED) in obese men and women., Methods: Thirty-seven men (n = 13) and women (n = 24) aged 50 +/- 9.8 years underwent 3 months of weight reduction on a VLED ( approximately 500 kcal/d) followed by 9 months on either a low-carbohydrate or low-fat weight maintenance diet ( approximately 1600 kcal/d). Concentrations of osteocalcin (OC) and C-terminal peptide of type I collagen (CTX) in serum were measured using enzyme-linked immunosorbent assay at baseline and at months 3, 6, and 12. Serum parathyroid (PTH) concentrations were measured using a chemiluminescent immunoassay at all 4 time points. Data were analyzed using a 3-factor-repeated measures analysis of variance., Results: Average weight loss was 19% +/- 3% and, during the 9-month weight maintenance period, average weight gain was approximately 3%, with no differences due to diet composition. Serum concentrations of OC and CTX significantly increased after weight reduction and remained elevated during weight maintenance. Serum PTH was reduced after weight loss. Percent changes in OC and CTX were correlated during weight maintenance (r = -0.437, p = 0.008), but not during weight loss. Percent changes in CTX and body weight were negatively correlated during weight loss (r = -0.474, p = 0.003) and maintenance (r = -0.455, p = 0.006)., Conclusions: Weight loss induced via a VLED may result in an imbalance between bone formation and resorption and accelerate remodeling. The deleterious effect of energy restriction on bone remodeling rate appears to persist during weight maintenance.

Background: Physical Activity Across the Curriculum (PAAC) was a three-year cluster randomized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children., Methods: Twenty-four elementary schools were cluster randomized to the Physical Activity Across the Curriculum intervention or served as control. All children in grades two and three were followed to grades four and five. Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers. Body Mass Index was the primary outcome, daily Physical activity and academic achievement were secondary outcomes., Results: The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9, respectively (NS). However, change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum. Schools with > or =75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had <75 min of Physical Activity Across the Curriculum (1.8+/-1.8 vs. 2.4+/-2.0, p=0.02). Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores., Conclusions: The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children. Additionally, 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index.

Objective: The purpose of this study was to compare the efficacy of two home-based weight loss interventions that differ only in the amount of outside support provided., Methods: This was a 12-week, randomized, controlled trial. One group received limited support (LWS, n = 35) via a single 10 min phone call each week while another group received no weekly support (NWS, n = 28). Both the LWS and NWS received pre-packaged meals (PM) and shakes. A third group served as control (CON, n = 30) and received no components of the intervention. Weight loss at 12 weeks was the primary outcome. Diet (PM, shake, and fruit/vegetable (F/V) intake) and physical activity (PA) were self-monitored, recorded daily and reported weekly. An exit survey was completed by participants in the intervention groups upon completion of the study., Results: Weight loss and percent weight loss in the LWS, NWS, and CON groups were 7.7 ± 4.4 kg (8.5 ± 4.2%), 5.9 ± 4.1 kg (6.0 ± 4.2%), and 0.3 ± 1.9 kg (0.4 ± 1.2%), respectively. The decrease in body weight and percent weight loss was significantly greater in the LWS and NWS groups when compared to the CON group and the percent weight loss was significantly greater in the LWS when compared to both the NWS and CON groups., Conclusion: A home-based weight loss program utilizing PM and shakes results in clinically significant percent weight loss and the addition of a brief weekly call promotes additional percent weight loss., (© 2009 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Long-term resistance training (RT) may result in a chronic increase in 24-h energy expenditure (EE) and fat oxidation to a level sufficient to assist in maintaining energy balance and preventing weight gain. However, the impact of a minimal RT program on these parameters in an overweight college-aged population, a group at high risk for developing obesity, is unknown., Purpose: We aimed to evaluate the effect of 6 months of supervised minimal RT in previously sedentary, overweight (mean +/- SEM, BMI = 27.7 +/- 0.5 kg x m(-2)) young adults (21.0 +/- 0.5 yr) on 24-h EE, resting metabolic rate (RMR), sleep metabolic rate (SMR), and substrate oxidation using whole-room indirect calorimetry 72 h after the last RT session., Methods: Participants were randomized to RT (one set, 3 d x wk(-1), three to six repetition maximums, nine exercises; N = 22) or control (C, N = 17) groups and completed all assessments at baseline and at 6 months., Results: There was a significant (P < 0.05) increase in 24-h EE in the RT (527 +/- 220 kJ x d(-1)) and C (270 +/- 168 kJ x d(-1)) groups; however, the difference between groups was not significant (P = 0.30). Twenty-four hours of fat oxidation (g x d(-1)) was not altered after RT; however, reductions in RT assessed during both rest (P < 0.05) and sleep (P < 0.05) suggested increased fat oxidation in RT compared with C during these periods. SMR (8.4 +/- 8.6%) and RMR (7.4 +/- 8.7%) increased significantly in RT (P < 0.001) but not in C, resulting in significant (P < 0.001) between-group differences for SMR with a trend for significant (P = 0.07) between-group differences for RMR., Conclusion: A minimal RT program that required little time to complete (11min per session) resulted in a chronic increase in energy expenditure. This adaptation in energy expenditure may have a favorable impact on energy balance and fat oxidation sufficient to assist with the prevention of obesity in sedentary, overweight young adults, a group at high risk for developing obesity.

A number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (DENV) infections, but little is known about the innate immune response of the mosquito vector Aedes aegypti to arbovirus infection. We present evidence here that a major component of the mosquito innate immune response, RNA interference (RNAi), is an important modulator of mosquito infections. The RNAi response is triggered by double-stranded RNA (dsRNA), which occurs in the cytoplasm as a result of positive-sense RNA virus infection, leading to production of small interfering RNAs (siRNAs). These siRNAs are instrumental in degradation of viral mRNA with sequence homology to the dsRNA trigger and thereby inhibition of virus replication. We show that although dengue virus type 2 (DENV2) infection of Ae. aegypti cultured cells and oral infection of adult mosquitoes generated dsRNA and production of DENV2-specific siRNAs, virus replication and release of infectious virus persisted, suggesting viral circumvention of RNAi. We also show that DENV2 does not completely evade RNAi, since impairing the pathway by silencing expression of dcr2, r2d2, or ago2, genes encoding important sensor and effector proteins in the RNAi pathway, increased virus replication in the vector and decreased the extrinsic incubation period required for virus transmission. Our findings indicate a major role for RNAi as a determinant of DENV transmission by Ae. aegypti.

The aim of this investigation was to develop an equation to estimate physical activity energy expenditure (PAEE) during a 10-min physically active academic lesson using The System for Observing Fitness Instruction Time (SOFIT) and demographic information. PAEE (portable indirect calorimeter) and physical activity (SOFIT) were simultaneously assessed in 38, 2nd through 5th grade children. PAEE and SOFIT were 3.04 +/- 1.1 (kcal/min) and 3.8 +/- 0.4 (score), respectively. PAEE was predicted from SOFIT score and body weight [PAEE (kcal/min) = (1.384*SOFIT + 0.084*weight (kg)--5.126), R = .81, SEE = 1.23 kcal/min]. PAEE measured by indirect calorimeter and predicted from SOFIT and body weight were 3.04 +/- 1.1 (kcal/min) and 3.04 +/- 0.9 kcal/min) respectively. SOFIT and body weight may provide a useful measure of PAEE associated with classroom based physical activity.

Background: To compare the effects of low versus recommended levels of dairy intake on weight maintenance and body composition subsequent to weight loss., Design and Methods: Two site (University of Kansas-KU; University of Tennessee-UT), 9 month, randomized trial. Weight loss was baseline to 3 months, weight maintenance was 4 to 9 months. Participants were maintained randomly assigned to low dairy (< 1 dairy serving/d) or recommended dairy (> 3 servings/d) diets for the maintenance phase. Three hundred thirty eight men and women, age: 40.3 +/- 7.0 years and BMI: 34.5 +/- 3.1, were randomized; Change in weight and body composition (total fat, trunk fat) from 4 to 9 months were the primary outcomes. Blood chemistry, blood pressure, resting metabolism, and respiratory quotient were secondary outcomes. Energy intake, calcium intake, dairy intake, and physical activity were measured as process evaluation., Results: During weight maintenance, there were no overall significant differences for weight or body composition between the low and recommended dairy groups. A significant site interaction occurred with the low dairy group at KU maintaining weight and body composition and the low dairy group at UT increasing weight and body fat. The recommended dairy group exhibited reductions in plasma 1,25-(OH)2-D while no change was observed in the low dairy group. No other differences were found for blood chemistry, blood pressure or physical activity between low and recommended dairy groups. The recommended dairy group showed significantly greater energy intake and lower respiratory quotient compared to the low dairy group., Conclusion: Weight maintenance was similar for low and recommended dairy groups. The recommended dairy group exhibited evidence of greater fat oxidation and was able to consume greater energy without greater weight gain compared to the low dairy group. Recommended levels of dairy products may be used during weight maintenance without contributing to weight gain compared to diets low in dairy products., Trial Registration: ClinicalTrials.gov NCT00686426.

We report a patient with herpes simplex virus (HSV) encephalitis presenting as recurrent syncope due to sinus node arrest. Although the patient's initial presentation suggested a primary cardiac cause, an eventual diagnosis of HSV encephalitis was supported by computed tomography scan and magnetic resonance imaging, and confirmed by HSV polymerase chain reaction. The mechanism of cardiac arrhythmias in HSV encephalitis remains unclear; however, cardiac monitoring should be considered in all patients in whom the diagnosis is suspected. With diagnosis and appropriate management, a permanent pacemaker is generally not indicated. This case report highlights the importance of considering potentially reversible causes of collapse secondary to sinus node dysfunction beyond primary cardiac causes.

Background: Physical Activity Across the Curriculum (PAAC) is a 3-year elementary school-based intervention to determine if increased amounts of moderate intensity physical activity performed in the classroom will diminish gains in body mass index (BMI). It is a cluster-randomized, controlled trial, involving 4905 children (2505 intervention, 2400 control)., Methods: We collected both qualitative and quantitative process evaluation data from 24 schools (14 intervention and 10 control), which included tracking teacher training issues, challenges and barriers to effective implementation of PAAC lessons, initial and continual use of program specified activities, and potential competing factors, which might contaminate or lessen program effects., Results: Overall teacher attendance at training sessions showed exceptional reach. Teachers incorporated active lessons on most days, resulting in significantly greater student physical activity levels compared to controls (p < 0.0001). Enjoyment ratings for classroom-based lessons were also higher for intervention students. Competing factors, which might influence program results, were not carried out at intervention or control schools or were judged to be minimal., Conclusion: In the first year of the PAAC intervention, process evaluation results were instrumental in identifying successes and challenges faced by teachers when trying to modify existing academic lessons to incorporate physical activity.

Selenium therapy in patients with severe sepsis improves clinical outcome and has been associated with increased activity of the selenoprotein glutathione peroxidase. However, the mechanism of the observed beneficial effects remains unclear. We determined the effect of selenium treatment on the monocyte adhesion molecule L-selectin and L-selectin-related monocyte functions in vitro and transferred our findings to an in vivo mouse model. Monocytes were purified, cultured, and incubated in the presence or absence of supplemented selenium and metalloproteinase (MP) inhibitors for up to 16 h. Expression of L-selectin was unaffected after 2 and 6 h but decreased after 16 h of incubation in the presence of selenium. Soluble L-selectin (sL-selectin) in the supernatant was determined by ELISA. A 2.3-fold increase as a result of shedding of L-selectin was observed after 16 h of selenium treatment. Addition of the MP inhibitors GM6001, TNF-alpha-converting enzyme inhibitor 2, or GW280264X strongly reduced selenium-induced L-selectin shedding, indicating a MP-dependent mechanism. The functional consequences of L-selectin shedding were examined in a flow chamber model. Selenium-treated monocytes showed significantly decreased rolling and adhesion to the L-selectin ligand Sialyl-Lewis(a) under conditions of venous shear stress (0.5 dyne/cm(2)). Selenium treatment of C57BL6 mice led to increased serum levels of sL-selectin, underscoring the in vivo relevance of our findings. We describe a selenium-induced down-regulation of L-selectin on monocytes as a consequence of MP-dependent shedding of this membrane-anchored adhesion molecule. The impairment of monocyte adhesion by selenium supplementation may represent an important, underlying mechanism for the modulation of inflammatory reactions in patients with severe sepsis.