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Cheryl A Gibson,1 Keith J August,2 Jerry L Greene,3 Stephen D Herrmann,4 Jaehoon Lee,5 Susan P Harvey,6 Kate Lambourne,3 Debra K Sullivan7 1Department of Internal Medicine, Division of General and Geriatric Medicine, University of Kansas Medical Center, KS, USA; 2Children's Mercy Hospital, MO, USA; 3Department of Health, Sport, and Exercise Sciences, University of Kansas, KS, USA; 4Children's Health Research Center, Sanford Research, SD, USA; 5Institute for Measurement, Methodology, Analysis and Policy, Texas Tech University, TX, USA; 6Center for Research on Learning, University of Kansas, KS, USA; 7Department of Dietetics and Nutrition, University of Kansas Medical Center, KS, USA Abstract: Changes in nutrient intake and decreased exercise resulting from cancer therapies as well as their side effects may be contributing factors in the increased body weight and differences in physical fitness observed in survivors of childhood acute lymphoblastic leukemia (ALL). This article will describe the study protocol for an intervention program designed to improve the physical activity and nutrition behaviors of ALL survivors. Twenty-four children aged between 4 years and 12 years with ALL will be randomized to a 6-month technology-based exercise and nutrition program (TLC4ALLKids) or to enhanced usual care (eUC). The participants randomized to the TLC4ALLKids will participate in weekly, 1-hour coaching sessions on nutrition and physical activity and 1-hour physical activity classes delivered by group video conferencing. Participants will be provided with iPad tablets loaded with video conferencing software and the Healthy Lifestyle Tracking calendar to track daily nutrition and physical activity goals and weight. Both groups will be provided with Fitbit™ Zip to monitor physical activity. To assess feasibility, participant recruitment (achievement of proposed sample size), attendance (per weekly online sessions/assessment sessions), and adherence (number of families at 3 and 6 months) will be evaluated. Outcome measures to assess the intervention will include anthropometrics (weight, height, and waist circumference), physical activity (accelerometry), energy and macronutrient intake (food records), sleep habits (Children's Sleep Habits Questionnaire), and quality of life (Pediatric Quality of Life Inventory) will be obtained at baseline, 3 months, and 6 months. Semi-structured interviews will be used to gather information about ways to improve the program and overcome barriers to participation. If successful, the TLC4ALLKids intervention will provide a means to educate and improve the health behaviors of ALL survivors that can be delivered remotely and conveniently to participants. Keywords: acute lymphoblastic leukemia, enhanced usual care, social cognitive theory

Background: Post-transplant weight gain affects 50-90% of kidney transplant recipients adversely affecting survival, quality of life, and risk for diabetes and cardiovascular disease. Diet modification and physical activity may help prevent post-transplant weight gain. Methods for effective implementation of these lifestyle modifications are needed. The objective of this study is to assess the feasibility and acceptability of a remotely delivered nutrition and physical activity intervention among kidney transplant recipients. Secondary aims were to estimate the effectiveness of the intervention in producing changes in physical activity, qualify of life, fruit and vegetable intake, and consumption of whole grains and water from baseline to 6 months., Methods: A randomized controlled study for stable kidney transplant recipients between 6 and 12 months post-transplantation was conducted. Participants were randomly assigned 1:1 to a technology-based, lifestyle modification program (intervention) or to enhanced usual care (control)., Results: The first 10 kidney transplant recipients screened were eligible and randomized into the intervention and control groups with no significant between-group differences at baseline. Health coaching attendance (78%) and adherence to reporting healthy behaviors (86%) were high. All participants returned for final assessments. The weight in controls remained stable, while the intervention arm showed weight gain at 3 and 6 months. Improvements were found for physical activity, quality of life, and fruit and vegetable intake in both groups. All participants would recommend the program to other transplant recipients., Conclusions: Our data suggest that a remotely delivered televideo nutrition and physical activity intervention is feasible and valued by patients. These findings will aid in the development of a larger, more prescriptive, randomized trial to address weight gain prevention., Trial Registration: Clinicaltrials.gov Identifier NCT03697317. Retrospectively registered on October 5, 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Only 43% of children in the U.S., ages 6-11 yrs., meet current physical activity (PA) guidelines. To satisfy the MVPA requirement, schools have begun incorporating MVPA in the form of activity breaks or MVPA academic lessons. We completed two, 3 academic-yr. cluster randomized trials (DK61489, DK85317) called "Physical Activity Across the Curriculum" (PAAC) which involved increasing MVPA in the classroom. Across 3-yrs. teachers in PAAC schools delivered ~60 min/wk. (12 min/day) of MVPA. Although short of our MVPA goal (20 min/d), the PAAC approach substantially increased in-school MVPA. Teacher reluctance to devote additional time to develop and integrate PA lessons into their curriculum was the overwhelming barrier to meeting the MVPA goal. Therefore, to reduce barriers to delivery of classroom PA we developed a 3-academic yr. cluster randomized trial (2 yrs. active intervention, 1 yr. follow-up) to compare the effectiveness and sustainability of technology delivered (PAAC-R) and classroom teacher delivered (PAAC-T) activity breaks for increasing classroom MVPA in elementary school students in grades 2 and 3 at baseline who will progress to grades 4-5. NCT registration: NCT03493139., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Adolescents with intellectual and developmental disabilities (IDD) are less physically active and have lower cardiovascular fitness compared with their typically developing peers. This population faces additional barriers to participation in moderate-to-vigorous physical activity (MVPA) such as reliance on parents, lack of peer-support, and lack of inclusive physical activity opportunities. Previous interventions to increase MVPA in adolescents with IDD have met with limited success, at least in part due to requiring parents to transport their adolescent to an exercise facility. We recently developed a remote system to deliver MVPA to groups of adolescents with IDD in their homes via video conferencing on a tablet computer. This approach eliminates the need for transportation and provides social interaction and support from both a health coach and other participants. We will conduct a 18-mo. trial (6 mos. active, 6 mos. maintenance, 6 mos. no-contact follow-up) to compare changes in objectively assessed MVPA in 114 adolescents with IDD randomized to a single level intervention delivered only to the adolescent (AO) or a multi-level intervention delivered to both the adolescent and a parent (A + P). Our primary aim is to compare increases in MVPA (min/d) between the AO and A + P groups from 0 to 6 mos. Secondarily we will compare changes in MVPA, sedentary time, cardiovascular fitness, muscular strength, motor ability, quality of life, and the percentage of adolescents achieving the US recommendation of 60 min. MVPA/d across 18 mos. We will also explore the influence of process variables/participant characteristics on changes in MVPA across 18 mos. NCT registration: NCT03684512., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Adults with Alzheimer's disease (AD) and their caregivers represent a segment of the population with low levels of moderate-intensity physical activity (MPA) and limited options for increasing MPA. The purpose of this study was to evaluate the feasibility of a group video conference approach for increasing MPA in adults with AD and their caregivers. Adults with AD and their caregivers attended 30-min group exercise sessions three times per week for 12 weeks. Exercise sessions and support sessions were delivered in their homes on a tablet computer over video conferencing software. Nine adults with AD/caregiver dyads enrolled, and seven completed the 12-week intervention. Adults with AD attended 77.3% of the group exercise sessions, and caregivers attended 79.2% of group exercise sessions. Weekly MPA increased in both adults with AD (49%) and caregivers (30%). Exercise delivered by group video conferencing is a feasible and potentially effective approach for increasing MPA in adults with AD and their caregivers.

Adults with intellectual and developmental disabilities (IDD) represent an underserved segment of the US population with a high prevalence of obesity and limited options for weight management. Previous research has demonstrated clinically meaningful weight loss of 7% of total body weight in in adults with IDD using an enhanced Stop Light Diet (eSLD) in combination with monthly at-home face-to-face (FTF) behavioral sessions, and a recommendation for increased physical activity. However, the time and cost associated with FTF delivery (travel + sessions) limits the potential for scaling and implementation and suggests the need for the evaluation of less costly and burdensome strategies for intervention delivery. Therefore, we will conduct a 24-mo. randomized trial to compare a weight management intervention (6 mos. weight loss, 12 mos. maintenance, 6 mos. no-contact follow-up) delivered to 120 overweight/obese adults with IDD in their home, either remotely (RD) using video conferencing on a tablet computer, or during FTF visits. Our primary aim is whether RD is non-inferior to FTF for weight loss (0-6 mos.). Secondarily, we will compare the RD and FTF groups on mean weight loss, the proportion of participants who achieve clinically meaningful weight loss, and changes in quality of life across 24 months. We will also conduct cost analysis, cost-effectiveness, and contingent valuation analyses to compare the RD and FTF groups., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Between 250,000 and 400,000 individuals in the United States are diagnosed with Down syndrome (DS). Nearly all adults with DS will develop Alzheimer's disease pathology starting in their thirties. Recent studies suggest that increased physical activity (PA) may be important for maintaining components of cognition, including memory., Objective: The purpose of this study was to evaluate changes in cognitive function after completion of a 12-week exercise intervention in adults with DS., Methods: Participants were randomized to attend 30-minute group exercise sessions 1 or 2 times a week for 12 weeks. The exercise sessions were delivered via video conferencing on a tablet computer to groups of 5-8 participants. Sessions consisted of aerobic based exercises such as walking and jogging to music, dancing, as well as strength based exercises such as vertical jumps, bicep curls, and squats. Cognitive function was measured at baseline and end of study using the Cantab Dementia Battery for iPads, which assessed the cognitive domains of memory, attention, and reaction time., Results: Twenty-seven participants (27.9 ± 7.1 years of age, 40.7% female) enrolled and completed the 12-week intervention. Participants randomized to 1 session/week averaged 26.6 ± 3.0 min/week of PA from the group exercise session. Participants randomized to 2 sessions/week averaged 57.7 ± 15.3 min/week of PA from the group exercise sessions. Participants improved their performance on the two memory variables (p = 0.048 and p = 0.069)., Conclusion: Increased exercise may have positive changes on memory and other cognitive functions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Globally, populations of diverse taxa have altered phenology in response to climate change. However, most research has focused on a single population of a given taxon, which may be unrepresentative for comparative analyses, and few long-term studies of phenology in ectothermic amniotes have been published. We test for climate-altered phenology using long-term studies (10-36 years) of nesting behavior in 14 populations representing six genera of freshwater turtles ( Chelydra , Chrysemys , Kinosternon , Malaclemys , Sternotherus , and Trachemys ). Nesting season initiation occurs earlier in more recent years, with 11 of the populations advancing phenology. The onset of nesting for nearly all populations correlated well with temperatures during the month preceding nesting. Still, certain populations of some species have not advanced phenology as might be expected from global patterns of climate change. This collection of findings suggests a proximate link between local climate and reproduction that is potentially caused by variation in spring emergence from hibernation, ability to process food, and thermoregulatory opportunities prior to nesting. However, even though all species had populations with at least some evidence of phenological advancement, geographic variation in phenology within and among turtle species underscores the critical importance of representative data for accurate comprehensive assessments of the biotic impacts of climate change.

Purpose: Adults with Down syndrome are less physically active than their typically developed peers. The purpose of this study was to assess the feasibility of delivering moderate-to- vigorous exercise sessions, led by a trained health educator using real-time video conferencing, to groups of young adults with Down syndrome in their homes., Methods: Participants were randomized to 30-minute group exercise sessions either 1 or 2 times a week delivered on an iPad mini tablet computer using the Zoom video conferencing application, and were asked to attend individual support/education sessions once a week using FaceTime ® on the iPad, for 12 weeks. Minutes of MVPA during all group sessions were assessed using a Fitbit Charge HR activity/heart rate monitor. Participants were also asked to complete weekly homework assignments involving MVPA., Results: Twenty-seven participants (n = 14,1 session·wk -1 , n =13, 2 sessions·wk -1 ), mean age 27.9 ± 7.1 yrs., ~ 41% female, enrolled in and completed the 12-wk. intervention. Attendance at group exercise and individual support/education sessions did not differ significantly between those randomized to 1 (exercise sessions =89.9 ± 8.8%, support/education sessions = 81.2 ±18.7%) or 2 sessions·wk -1 (exercise sessions = 88.8 ± 7.7%; p =0.79, support/education sessions= 86.0 ± 20.9%; p =0.87). Participants averaged 27.7 ± 5.7 mins·session -1 of MVPA with no significant difference between the 1 (26.6 ± 3.0 mins·session -1 ) and 2 session·wk -1 groups (28.8 ± 7.7 mins·session -1 , p =0.16). The completion rate for homework assignments did not differ significantly between the 1 (21.4 ± 26.3%) and 2 session·wk -1 groups (37.7 ± 21.7%, p =0.28)., Conclusion: Exercise delivered by group video conferencing may be a feasible and potentially effective approach for increasing MVPA in adults with Down syndrome., Competing Interests: Conflict of Interest No authors report any conflicts of interest, and the results of this study do not constitute endorsement of ACSM.

Research in education and developmental psychology indicates that behavioral engagement in learning is a critical predictor of children's academic success. In an effort to improve academic achievement, school administrators are continually in search of methods to increase behavioral engagement. Previous research has indicated that classroom-based physical activity (PA) lessons have a positive impact on academic achievement. However, little research has been done in assessing the impact of such interventions on the behavioral engagement of students with learning behavior difficulties. This study assesses the impact of classroom-based PA on teacher-rated classroom behaviors of students with identified learning behavior difficulties. Two schools (one intervention, one control) participating in a larger, cluster-randomized trial provided scores on a teacher-administered classroom behavior scale. This scale was used to collect information on 15 characteristics identified as being essential to behavioral engagement. Participants included male and female students in second and third grade classrooms who were identified by their classroom teacher and school counselor as having difficulties with learning behaviors. Mixed linear modeling for repeated measures was used to examine the changes over time in the classroom behavior scores. The intervention group showed significant improvement over time in classroom behavior while the control group showed no change or a slight degradation over time (i.e., group × time interaction, F [2132] = 4.52, p  = 0.01). Schools must meet the diverse needs of students today, including those who exhibit less than optimal learning behaviors. Combined with the evidence that PA is linked to several health and cognitive-behavior benefits, providing classroom-based PA that is incorporated within the curriculum provides common ground for all students to participate. It is a potential solution to increasing behavioral engagement, and in turn stimulating and enhancing learning., Competing Interests: This study was approved by the University of Kansas Institutional Review Board, HSC #19732. All parents provided voluntary consent for their children to participate.The authors declare that they have no competing interests.

Physical activity (PA) rates of adolescents with intellectual and developmental disabilities (IDD) are low and effective strategies for increasing PA are limited. The purpose of this study was to assess the feasibility of a group-based PA intervention that was delivered remotely to adolescents with IDD. Participants attended 30-min group PA sessions 3 times a week. PA sessions were delivered in their homes by video conferencing on a tablet computer. Thirty-one participants enrolled and 29 completed the 12-week intervention. Participants attended 77.2% ± 20.8% of scheduled sessions and averaged 26.7 ± 2.8 min of PA/session, with 11.8 ± 4.8 min at moderate- to vigorous intensity. Group-based PA delivered remotely may be a feasible approach for the promotion of PA in adolescents with IDD.

Developing reliable, predictive kinetic models of metabolism is a difficult, yet necessary, priority toward understanding and deliberately altering cellular behavior. Constraint-based modeling has enabled the fields of metabolic engineering and systems biology to make great strides in interrogating cellular metabolism but does not provide sufficient insight into regulation or kinetic limitations of metabolic pathways. Moreover, the growth-optimized assumptions that constraint-based models often rely on do not hold when studying stationary or persistor cell populations. However, developing kinetic models provides many unique challenges, as many of the kinetic parameters and rate laws governing individual enzymes are unknown. Ensemble modeling (EM) was developed to circumnavigate this challenge and effectively sample the large kinetic parameter solution space using consistent experimental datasets. Unfortunately, EM, in its base form, requires long solve times to complete and often leads to unstable kinetic model predictions. Furthermore, these limitations scale prohibitively with increasing model size. As larger metabolic models are developed with increasing genetic information and experimental validation, the demand to incorporate kinetic information increases. Therefore, in this work, we have begun to tackle the challenges of EM by introducing additional steps to the existing method framework specifically through reducing computation time and optimizing parameter sampling. We first reduce the structural complexity of the network by removing dependent species, and second, we sample locally stable parameter sets to reflect realistic biological states of cells. Lastly, we presort the screening data to eliminate the most incorrect predictions in the earliest screening stages, saving further calculations in later stages. Our complementary improvements to this EM framework are easily incorporated into concurrent EM efforts and broaden the application opportunities and accessibility of kinetic modeling across the field., (Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

We compared changes in academic achievement across 3years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention (A+PAAC), in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity (MVPA) compared to a non-intervention control. Elementary schools in eastern Kansas (n=17) were cluster randomized to A+PAAC (N=9, target ≥100min/week) or control (N=8). Academic achievement (math, reading, spelling) was assessed using the Wechsler Individual Achievement Test-Third Edition (WIAT-III) in a sample of children (A+PAAC=316, Control=268) in grades 2 and 3 at baseline (Fall 2011) and repeated each spring across 3years. On average 55min/week of A+PACC lessons were delivered each week across the intervention. Baseline WIAT-III scores (math, reading, spelling) were significantly higher in students in A+PAAC compared with control schools and improved in both groups across 3years. However, linear mixed modeling, accounting for baseline between group differences in WIAT-III scores, ethnicity, family income, and cardiovascular fitness, found no significant impact of A+PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions. A+PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls. Our target of 100min/week of active lessons was not achieved; however, students attending A+PAAC schools received an additional 55min/week of MVPA which may be associated with both physical and mental health benefits, without a reduction in time devoted to academic instruction., (Copyright © 2017. Published by Elsevier Inc.)

Adolescents with intellectual and developmental disabilities (IDD) are an underserved group in need of weight management. However, information regarding effective weight management for this group is limited, and is based primarily on results from small, non-powered, non-randomized trials that were not conducted in accordance with current weight management guidelines. Additionally, the comparative effectiveness of emerging dietary approaches, such as portion-controlled meals (PCMs) or program delivery strategies such as video chat using tablet computers have not been evaluated. Therefore, we will conduct an 18month trial to compare weight loss (6months) and maintenance (7-18months) in 123 overweight/obese adolescents with mild to moderate IDD, and a parent, randomized to a weight management intervention delivered remotely using FaceTime™ on an iPad using either a conventional meal plan diet (RD/CD) or a Stop Light diet enhanced with PCMs (RD/eSLD), or conventional diet delivered during face-to-face home visits (FTF/CD). This design will provide an adequately powered comparison of both diet (CD vs. eSLD) and delivery strategy (FTF vs. RD). Exploratory analyses will examine the influence of behavioral session attendance, compliance with recommendations for diet (energy intake), physical activity (min/day), self-monitoring of diet and physical activity, medications, and parental variables including diet quality, physical activity, baseline weight, weight change, and beliefs and attitudes regarding diet and physical activity on both weight loss and maintenance. We will also complete a cost and contingent valuation analysis to compare costs between RD and FTF delivery., (Copyright © 2016. Published by Elsevier Inc.)

A large number of individuals experience mental health disorders, with cognitive behavioral therapy (CBT) emerging as a standard practice for reduction in psychiatric symptoms, including stress, anger, anxiety, and depression. However, CBT is associated with significant patient dropout and lacks the means to provide objective data regarding a patient's experience and symptoms between sessions. Emerging wearables and mobile health (mHealth) applications represent an approach that may provide objective data to the patient and provider between CBT sessions. Here, we describe the development of a classifier of real-time physiological stress in a healthy population (n = 35) and apply it in a controlled clinical evaluation for armed forces veterans undergoing CBT for stress and anger management (n = 16). Using cardiovascular and electrodermal inputs from a wearable device, the classifier was able to detect physiological stress in a non-clinical sample with accuracy greater than 90%. In a small clinical sample, patients who used the classifier and an associated mHealth application were less likely to discontinue therapy (p = 0.016, d = 1.34) and significantly improved on measures of stress (p = 0.032, d = 1.61), anxiety (p = 0.050, d = 1.26), and anger (p = 0.046, d = 1.41) compared to controls undergoing CBT alone. Given the large number of individuals that experience mental health disorders and the unmet need for treatment, especially in developing nations, such mHealth approaches have the potential to provide or augment treatment at low cost in the absence of in-person care.

Background: There is limited data regarding objectively measured energy cost and intensity of classroom instruction. Therefore, the purpose of current study was to objectively measure energy cost and subsequently calculate MET values using a portable indirect calorimeter (IC) for both normal classroom instruction (NCI) and active classroom instruction (ACI)., Methods: We assessed energy expenditure (EE) and intensity levels (METs) in elementary school children (17 boys and 15 girls) using an IC (COSMED K4b2). Independent t-tests were used to evaluate potential sex and grade level differences for age, BMI, VO2, EE, and METs., Results: The average EE for NCI and ACI were 1.8 ± 0.4 and 3.9 ± 1.0, respectively. The average intensity level for NCI and ACI were 1.9 ± 0.4 and 4.2 ± 0.9 METs, respectively., Conclusions: PA delivered through ACI can elicit EE at a moderate intensity level. These results provide evidence for ACI as a convenient/feasible avenue for increasing PA in youth without decreasing instruction time.

Assessing predictors of intention to circumcise can help to identify effective strategies for increasing uptake of voluntary medical male circumcision (VMMC). Grounded in the theory of reasoned action (TRA), the current study of uncircumcised males ages 13-29 in Swaziland (N = 1,257) employed multivariate logistic regression to determine predictors of VMMC intention. The strongest predictors were strongly disagreeing/disagreeing that sex was more painful for a circumcised man (odds ratio [OR] = 4.37; p = < .007), a Christian man should not get circumcised (OR = 2.47; p < .001), and circumcision makes penetration more painful and difficult (OR = 2.44; p = .007). Several beliefs about enhanced sexual performance, normative beliefs (parents, sexual partner, and friends), and non-TRA-related factors (e.g., importance of plowing season to daily schedule) were also statistically significant predictors. TRA proved a useful theory to explore young men's intention to circumcise and can help inform interventions aimed at increasing uptake of VMMC.

Protein S-nitrosylation is considered as one of the molecular mechanisms by which nitric oxide regulates signaling events and protein function. The present review presents an updated method which allows for the site-specific detection of S-nitrosylated proteins in vivo. The method is based on enrichment of S-nitrosylated proteins or peptides using organomercury compounds followed by LC-MS/MS detection. Technical aspects for determining the reaction and binding efficiency of the mercury resin that assists enrichment of S-nitrosylated proteins are presented and discussed. In addition, emphasis is given to the specificity of the method by providing technical details for the generation of four chemically distinct negative controls. Finally it is provided an overview of the key steps for generation and evaluation of mass spectrometry derived data., (Copyright © 2012 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.

Cysteine S-nitrosylation is a posttranslational modification by which nitric oxide regulates protein function and signaling. Studies of individual proteins have elucidated specific functional roles for S-nitrosylation, but knowledge of the extent of endogenous S-nitrosylation, the sites that are nitrosylated, and the regulatory consequences of S-nitrosylation remains limited. We used mass spectrometry-based methodologies to identify 1011 S-nitrosocysteine residues in 647 proteins in various mouse tissues. We uncovered selective S-nitrosylation of enzymes participating in glycolysis, gluconeogenesis, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that this posttranslational modification may regulate metabolism and mitochondrial bioenergetics. S-nitrosylation of the liver enzyme VLCAD [very long chain acyl-coenzyme A (CoA) dehydrogenase] at Cys(238), which was absent in mice lacking endothelial nitric oxide synthase, improved its catalytic efficiency. These data implicate protein S-nitrosylation in the regulation of β-oxidation of fatty acids in mitochondria.

Background: A biochemical pathway by which nitric oxide accomplishes functional diversity is the specific modification of protein cysteine residues to form S-nitrosocysteine. This post-translational modification, S-nitrosylation, impacts protein function, interactions and location. However, comprehensive studies exploring protein signaling pathways or interrelated protein clusters that are regulated by S-nitrosylation have not been performed on a global scale., Scope of Review: To provide insights to these important biological questions, sensitive, validated and quantitative proteomic approaches are required. This review summarizes current approaches for the global identification of S-nitrosylated proteins., Major Conclusions: The application of novel methods for identifying S-nitrosylated proteins, especially when combined with mass-spectrometry based proteomics to provide site-specific identification of the modified cysteine residues, promises to deliver critical clues for the regulatory role of this dynamic posttranslational modification in cellular processes., General Significance: Though several studies have established S-nitrosylation as a regulator of protein function in individual proteins, the biological chemistry and the structural elements that govern the specificity of this modification in vivo are vastly unknown. Additionally, a gap in knowledge exists concerning the potential global regulatory role(s) this modification may play in cellular physiology. By further studying S-nitrosylation at a global scale, a greater appreciation of nitric oxide and protein S-nitrosylation in cellular function can be achieved. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one of the molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed the site of S-nitrosylation in 328 peptides in 192 proteins endogenously modified in WT mouse liver. Structural analyses revealed that S-nitrosylated cysteine residues were equally distributed in hydrophobic and hydrophilic areas of proteins with an average predicted pK(a) of 10.01 ± 2.1. S-nitrosylation sites were over-represented in α-helices and under-represented in coils as compared with unmodified cysteine residues in the same proteins (χ(2) test, P < 0.02). A quantile-quantile probability plot indicated that the distribution of S-nitrosocysteine residues was skewed toward larger surface accessible areas compared with the unmodified cysteine residues in the same proteins. Seventy percent of the S-nitrosylated cysteine residues were surrounded by negatively or positively charged amino acids within a 6-Å distance. The location of cysteine residues in α-helices and coils in highly accessible surfaces bordered by charged amino acids implies site directed S-nitrosylation mediated by protein-protein or small molecule interactions. Moreover, 13 modified cysteine residues were coordinated with metals and 15 metalloproteins were endogenously modified supporting metal-catalyzed S-nitrosylation mechanisms. Collectively, the endogenous S-nitrosoproteome in the liver has structural features that accommodate multiple mechanisms for selective site-directed S-nitrosylation.

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.

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.

Published research has indicated that ethyl 2-methylpropanoate, ethyl 2-methybutanaote, ethyl 3-methylbutanoate, hexanoic acid, butanoic acid, and 3-methylbutanoic acid are responsible for fruity fermented (FF) off-flavor; however, these compounds were identified in samples that were artificially created by curing immature peanuts at a constant high temperature. The objective of this study was to characterize the volatile compounds contributing to naturally occurring FF off-flavor. Volatile compounds of naturally occurring FF and no-FF samples were characterized using solvent-assisted flavor evaporation (SAFE), solid phase microextraction (SPME), gas chromatography-olfactometry (GC-O), and gas chromatography-mass spectrometry (GC-MS). Aroma extract dilution analysis (AEDA) identified 12 potent aroma active compounds, none of which were the previously identified esters, with no consistent differences among the aroma active compounds in no-FF and FF samples. Hexanoic acid alone was identified in the naturally occurring FF sample using the SAFE GC-MS methodology, whereas two of the three previously identified esters were identified in natural and artificially created samples. The same two esters were confirmed by SPME GC-MS in natural and artificially created samples. This study demonstrated the need for caution in the direct application of data from artificially created samples until those compounds are verified in natural samples. However, these results suggest that a laboratory method using SPME-GC techniques could be developed and correlated on an ester concentration versus FF intensity basis to provide an alternative to sensory analysis for detection of FF off-flavor in peanut lots.

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.

In this article we work the tensions between the way clinical medicine and public health necessarily construct the problem of "repetition" in the context of a sexually transmitted disease (STD) clinic and the ways patients narrate their illness experiences. This tension-between clinical and epidemiological exigencies and the messiness of lived experience-is a recurring theme of work conducted at the intersections of epidemiology, anthropology, and clinical medicine. Clinically, repeated infections are a threat to the individual body and to "normal" biological processes like reproduction. From a public health perspective, "repeaters" are imagined to be part of a "core group" that keeps infections in circulation, endangering the social body. Yet patients' accounts are anchored in particular social histories, and their experiences rely on different time scales than those implicated in either of these types of readings. Extended analyses are provided of two such accounts: one in which repetition can be "read" as part of a performance of recovery, and one in which repetition is bound up in the effort to avoid becoming the involuntary subject of institutionally administered intervention. We argue the need to open up the category of repeaters to include the social and draw on work by Cheryl Mattingly to suggest that one way to do this in the context of the STD clinic might be to adopt forms of therapeutic practice that make use of interpretive, in addition to technical, skills.

Despite the continuing loss of wetland habitats and associated declines in amphibian populations, attempts to translate wetland losses into measurable losses to ecosystems have been lacking. We estimated the potential productivity from the amphibian community that would be compromised by the loss of a single isolated wetland that has been protected from most industrial, agricultural, and urban impacts for the past 54 years. We used a continuous drift fence at Ellenton Bay, a 10-ha freshwater wetland on the Savannah River Site, near Aiken, South Carolina (U.S.A.), to sample all amphibians for 1 year following a prolonged drought. Despite intensive agricultural use of the land surrounding Ellenton Bay prior to 1951, we documented 24 species and remarkably high numbers and biomass of juvenile amphibians (>360,000 individuals; >1,400 kg) produced during one breeding season. Anurans (17 species) were more abundant than salamanders (7 species), comprising 96.4% of individual captures. Most (95.9%) of the amphibian biomass came from 232095 individuals of a single species of anuran (southern leopard frog[Rana sphenocephala]). Our results revealed the resilience of an amphibian community to natural stressors and historical habitat alteration and the potential magnitude of biomass and energy transfer from isolated wetlands to surrounding terrestrial habitat. We attributed the postdrought success of amphibians to a combination of adult longevity (often >5 years), a reduction in predator abundance, and an abundance of larval food resources. Likewise, the increase of forest cover around Ellenton Bay from <20% in 1951 to >60% in 2001 probably contributed to the long-term persistence of amphibians at this site. Our findings provide an optimistic counterpoint to the issue of the global decline of biological diversity by demonstrating that conservation efforts can mitigate historical habitat degradation.

Rationale: Evidence indicates that social and environmental enrichment can influence the functional maturation of the central nervous system and may affect an organism's sensitivity to centrally acting drugs., Objective: The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to mu-opioids possessing a range of relative efficacies at the mu-receptor., Methods: Rats were obtained at weaning (21 days) and divided into two groups immediately upon arrival. Isolated rats were housed individually in opaque laboratory cages with no visual or tactile contact with other rats; enriched rats were housed socially in groups of four in large cages and given various novel objects on a daily basis. After 6 weeks under these conditions, the effects of morphine, levorphanol, buprenorphine, butorphanol, and nalbuphine were examined in the warm-water, tail-withdrawal procedure and the place-conditioning procedure., Results: In the tail-withdrawal procedure, isolated and enriched rats did not differ in sensitivity to morphine (1.0-30 mg/kg) and levorphanol (0.3-10 mg/kg), but enriched rats were more sensitive to buprenorphine (0.03-3.0 mg/kg), butorphanol (0.3-30 mg/kg), and nalbuphine (0.3-30 mg/kg). In drug combination tests, butorphanol and nalbuphine antagonized the effects of morphine in isolated rats under conditions in which they produced high levels of antinociception in enriched rats. In the place-conditioning procedure, doses of 10 morphine and 3.0 levorphanol established a place preference in both groups of rats, whereas doses of 0.3 buprenorphine, 3.0 butorphanol, and 10 nalbuphine established a place preference only in enriched rats., Conclusions: These findings may be taken as evidence that enriched rats are more sensitive than isolated rats to the effects of lower-efficacy mu-opioids and that social and environmental enrichment leads to functional alterations in opioid receptor populations.

Bupropion is an increasingly prescribed agent to aid in smoking cessation. However it has important drug-drug interactions related to the cytochrome P450 system. One of these is its inhibition of the metabolism of the commonly used beta-blocker, metoprolol. The authors describe a case of severe bradycardia related to the addition of bupropion to the medical regimen of a patient on metoprolol.

The purpose of the present study was to examine sensitivity to the antinociceptive effects of kappa opioids during chronic treatment with the nonselective opioid antagonist naltrexone. In a warm-water tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from water maintained at 50 and 55 degrees C were recorded. Prior to chronic treatment, spiradoline, U50,488 and (-)-pentazocine produced dose-dependent increases in tail-withdrawal latencies at both 50 and 55 degrees C. Chronic treatment with 3.0 mg/kg naltrexone twice daily (b.i.d.) failed to alter sensitivity to the antinociceptive effects of spiradoline when tested 24 h following naltrexone administration. When the maintenance dose of naltrexone was increased to 30 mg/kg b.i.d., sensitivity to the effects of spiradoline was reduced when tested 24 h after naltrexone administration, but enhanced when tested 48 h after naltrexone administration. Enhanced sensitivity was also observed to the antinociceptive effects of U50,488 and (-)-pentazocine when tested 48 h after chronic treatment with 30 mg/kg naltrexone. After termination of chronic treatment, sensitivity to the antinociceptive effects of spiradoline, U50,488 and (-)-pentazocine returned to that originally observed prior to naltrexone treatment. These data indicate that chronic naltrexone treatment enhances sensitivity to the antinociceptive effects of kappa opioids, and that this effect is both dose and time dependent.

/ We examined data relative to species abundance, distribution, anddiversity patterns of reptiles and amphibians to determine how perceptionschange over time and with level of sampling effort. Location data werecompiled on more than one million individual captures or observations of 98species during a 44-year study period on the US Department of Energy's(DOE) Savannah River Site National Environmental Research Park (SRS-NERP) inSouth Carolina. We suggest that perceptions of herpetofaunal speciesdiversity are strongly dependent on level of effort and that land managementdecisions based on short-term data bases for some faunal groups could resultin serious errors in environmental management. We provide evidence thatacquiring information on biodiversity distribution patterns is compatiblewith multiyear spatially extensive research programs and also provide aperspective of what might be achieved if long-term, coordinated researchefforts were instituted nationwide.To conduct biotic surveys on government-managed lands, we recommend revisionsin the methods used by government agencies to acquire and report biodiversitydata. We suggest that government and industry employees engaged inbiodiversity survey efforts develop proficiency in field identification forone or more major taxonomic groups and be encouraged to measure the status ofpopulations quantitatively with consistent and reliable methodologies. Wealso suggest that widespread academic cooperation in the dissemination ofinformation on regional patterns of biodiversity could result byestablishment of a peer-reviewed, scientifically rigorous journal concernedwith status and trends of the biota of the United States. KEY WORDS: Abundance; Amphibian; Biodiversity; Distribution; Landmanagement; Reptile

T lymphocyte receptors CD28 and CTLA-4 bind costimulatory molecules CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells and regulate T cell activation. While distinct functional roles have been ascribed to each of these molecules, little is known about how they interact. To better characterize these interactions, we have used surface plasmon resonance to perform equilibrium and kinetic binding analyses of extracellular fragments of CD28/CTLA-4/CD80/CD86. We show that CTLA-4 and CD28 binding are both characterized by rapid kinetic on-rates and rapid dissociation rates. Native disulfide-linked homodimers of CD28 and CTLA-4 bound with two kinetically distinct binding sites, one of high avidity and slow dissociation and one of low avidity and more rapid dissociation. Monomeric CTLA-4 bound only with low affinity and rapid dissociation. Therefore, covalent dimerization of CTLA-4 is required for its high avidity binding. Oligomerization of CD80/CD86 is also required for high avidity CTLA-4 binding since CTLA-4 bound with low avidity to monomeric CD86. This contrasts with the ability of CD80/CD86 on antigen-presenting cells to bind CTLA4Ig with high avidity and predicts their organization as oligomers or clusters that permit multivalent binding. Thus, covalent receptor dimerization and ligand oligomerization are two key features of the CD28/CTLA-4/CD80/CD86 receptor system that control ligand binding and may regulate signal transduction by controlling the duration of receptor occupancy.

B7-0 or B7-2 (CD86) is a T cell costimulatory molecule that binds the same receptors (CD28 and CTLA-4) as B7-1 (CD80), but shares with it only approximately 25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (within approximately 2- to 3-fold) overall receptor binding and T cell costimulatory properties as CD80. However, CD80 and CD86 did not bind equivalently to CTLA-4: CD80 bound Y100A, a form of CTLA4lg with a mutation in the CDR3-like region, > 200-fold better than did CD86; inhibition of CD80-mediated cellular responses required approximately 100-fold lower CTLA4lg concentrations; and CD80-CTLA4lg complexes dissociated 5- to 8-fold more slowly, Thus, CD80 and CD86 utilize different binding determinants and have different kinetics of binding to CD28 and CTLA-4.

T cell costimulation by molecules on the antigen presenting cell (APC) is required for optimal T cell proliferation. The B7 molecule on APC binds the T lymphocyte receptor CD28, triggering increased interleukin 2 (IL-2) production and subsequent T cell proliferation. CTLA-4 is a predicted T cell membrane receptor homologous to CD28, which also binds the B7 counter receptor, but whose distribution and function are unknown. Here we have developed monoclonal antibodies (mAbs) specific for CTLA-4 and have investigated these questions. mAbs were produced that bound CTLA-4 but not CD28, and that blocked binding of CTLA-4 to B7. CTLA-4 expression as measured by these mAbs was virtually undetectable on resting T cells, but was increased several hundred-fold during T cell activation. On activated lymphocytes, CTLA-4 was expressed equally on CD4+ and CD8+ T cell subsets and was coexpressed with CD25, CD28, and CD45RO. CTLA-4 expression was lower than that of CD28, reaching a maximum of approximately 1/30-50 the level of CD28. Despite its lower expression, CTLA-4 was responsible for much of the B7 binding by large activated T cells. Anti-CTLA-4 mAb 11D4 and anti-CD28 mAb 9.3 acted cooperatively to inhibit T cell adhesion to B7, and to block T cell proliferation in primary mixed lymphocyte culture. When coimmobilized with anti T cell receptor (TCR) mAb, anti-CTLA-4 mAbs were less effective than anti-CD28 mAb 9.3 at costimulating proliferation of resting or activated T cells. However, coimmobilized combinations of anti-CD28 and anti-CTLA-4 were synergistic in their ability to augment anti-TCR-induced proliferation of preactivated CD4+ T cells. These results indicate that CTLA-4 is coexpressed with CD28 on activated T lymphocytes and cooperatively regulates T cell adhesion and activation by B7.

In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatment in vivo suppressed T cell-dependent antibody responses to sheep erythrocytes or keyhole limpet hemocyanin. Large doses of CTLA4Ig suppressed responses to a second immunization. Thus, costimulation by B7 is important for humoral immune responses in vivo, and interference with costimulation may be useful for treatment of antibody-mediated autoimmune disease.

[35S]L-Homocysteine thiolactone ([35S]L-HCTL) was synthesized and its biodistribution evaluated as a potential brain radioprotective agent and as a tissue hypoxia marker. Drug uptake in mouse brain exceeded that in s.c. tumor 3 h post injection only. Multiple indicator dilution experiments in the rabbit heart indicate that membrane permeability of [35S]L-HCTL does not limit its usefulness as a hypoxia marker. In addition, a positive correlation was observed between regional coronary blood flow and myocardial content of [35S]adenosylhomocysteine formed from [35S]homocysteine and adenosine.