SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

BACKGROUND: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions. METHODS: This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy. CONCLUSION: Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments.

Low myoglobin concentration in skeletal muscle of elite cyclists is associated with low mRNA expression levels.

Myoglobin is essential for oxygen transport to the muscle fibers. However, measurements of myoglobin (Mb) protein concentrations within individual human muscle fibers are scarce. Recent observations have revealed surprisingly low Mb concentrations in elite cyclists, however it remains unclear whether this relates to Mb translation, transcription and/or myonuclear content. The aim was to compare Mb concentration, Mb messenger RNA (mRNA) expression levels and myonuclear content within muscle fibers of these elite cyclists with those of physically-active controls. Muscle biopsies were obtained from m. vastus lateralis in 29 cyclists and 20 physically-active subjects. Mb concentration was determined by peroxidase staining for both type I and type II fibers, Mb mRNA expression level was determined by quantitative PCR and myonuclear domain size (MDS) was obtained by immunofluorescence staining. Average Mb concentrations (mean ± SD: 0.38 ± 0.04 mM vs. 0.48 ± 0.19 mM; P = 0.014) and Mb mRNA expression levels (0.067 ± 0.019 vs. 0.088 ± 0.027; P = 0.002) were lower in cyclists compared to controls. In contrast, MDS and total RNA per mg muscle were not different between groups. Interestingly, in cyclists compared to controls, Mb concentration was only lower for type I fibers (P < 0.001), but not for type II fibers (P > 0.05). In conclusion, the lower Mb concentration in muscle fibers of elite cyclists is partly explained by lower Mb mRNA expression levels per myonucleus and not by a lower myonuclear content. It remains to be determined whether cyclists may benefit from strategies that upregulate Mb mRNA expression levels, particularly in type I fibers, to enhance their oxygen supply.

Brain structural and functional connectivity and network organization in cerebral palsy: A scoping review.

AIM: To explore altered structural and functional connectivity and network organization in cerebral palsy (CP), by clinical CP subtype (unilateral spastic, bilateral spastic, dyskinetic, and ataxic CP). METHOD: PubMed and Embase databases were systematically searched. Extracted data included clinical characteristics, analyses, outcome measures, and results. RESULTS: Sixty-five studies were included, of which 50 investigated structural connectivity, and 20 investigated functional connectivity using functional magnetic resonance imaging (14 studies) or electroencephalography (six studies). Five of the 50 studies of structural connectivity and one of 14 of functional connectivity investigated whole-brain network organization. Most studies included patients with unilateral spastic CP; none included ataxic CP. INTERPRETATION: Differences in structural and functional connectivity were observed between investigated clinical CP subtypes and typically developing individuals on a wide variety of measures, including efferent, afferent, interhemispheric, and intrahemispheric connections. Directions for future research include extending knowledge in underrepresented CP subtypes and methodologies, evaluating the prognostic potential of specific connectivity and network measures in neonates, and understanding therapeutic effects on brain connectivity.

The measurement of proprioceptive accuracy: A systematic literature review.

BACKGROUND: Proprioceptive accuracy refers to the individual's ability to perceive proprioceptive information, that is, the information referring to the actual state of the locomotor system, which originates from mechanoreceptors located in various parts of the locomotor system and from tactile receptors located in the skin. Proprioceptive accuracy appears to be an important aspect in the evaluation of sensorimotor functioning; however, no widely accepted standard assessment exists. In this systematic review, our goal was to identify and categorize different methods that are used to assess different aspects of proprioceptive accuracy. METHODS: A literature search was conducted in 5 different databases (PubMed, SPORTDiscus, PsycINFO, ScienceDirect, and SpringerLink). RESULTS: Overall, 1139 scientific papers reporting 1346 methods were included in this review. The methods assess 8 different aspects of proprioception: (a) the perception of joint position, (b) movement and movement extent, (c) trajectory, (d) velocity, and the sense of (e) force, (f) muscle tension, (g) weight, and (h) size. They apply various paradigms of psychophysics (i.e., the method of adjustment, constant stimuli, and limits). CONCLUSION: As the outcomes of different tasks with respect to various body parts show no associations (i.e., proprioceptive accuracy is characterized by site-specificity and method-specificity), the appropriate measurement method for the task needs to be chosen based on theoretical considerations and/or ecological validity.

A Mixed-Methods Description of the Home Physical Activity Environments of Racially/Ethnically Diverse and Immigrant/Refugee Children.

Disparities in childhood obesity prevalence by race/ethnicity remain high. Physical activity is an important factor to consider, however little is known about how physical activity resources in the home environment and neighborhood differ by race/ethnicity. This study examines the physical activity environments in the homes and neighborhoods of diverse households using both quantitative and qualitative data. Home visits were conducted with 150 families, and accelerometry data was collected for both parents and children (5-7 years old). Qualitative interviews were also conducted with parents, which provided context to quantitative data. Racial/ethnic differences were found for physical activity, sedentary behavior, and family-level resources for physical activity (P < .05). There were also differences by race/ethnicity in neighborhood physical activity promoters and perceived lack of neighborhood safety (P < .05). This study is important in informing providers and future interventions of the varying promoters and barriers to optimal physical activity that exist across race/ethnicity.

Exergaming improves balance in children with spastic cerebral palsy with low balance performance: results from a multicenter controlled trial.

PURPOSE: Previous studies investigating the effectiveness of exergame balance-training (using video-games) in children with cerebral palsy (CP) yielded inconsistent results that could be related to underpowered studies. Therefore, in this multicenter intervention study, we investigated whether exergaming improves balance clinically in spastic CP. MATERIALS AND METHODS: In total, 35 children with unilateral or bilateral spastic CP (GMFCS-level I-II) were included (age-range: 7-16 years); 16 at VUMC (trial: NTR6034), 19 at UHG (trial: NCT03219112). All participants received care as usual. The intervention group (n = 24) additionally performed exergame-training; 6-8 weeks home-based X-box One Kinect training focused on balance. Balance performance was assessed with the pediatric balance scale (PBS) and two subscales of the Bruininks-Oseretsky Test of Motor Proficiency-2nd edition ("balance" [BOTbal] and "running speed and agility" [BOTrsa]). Mixed model ANOVAs with between and within factors were used to test differences between and within groups. RESULTS: On group level, no post-intervention differences were found between the intervention and control group (PBS: p = 0.248, ηp2 = 0.040; BOTbal: p = 0.374, ηp2 = 0.024; BOTrsa: p = 0.841, ηp2 = 0.001). Distribution of CP-symptoms (unilateral versus bilateral) did not affect training (PBS: p = 0.373, ηp2 = 0.036; BOTbal: p = 0.127, ηp2 = 0.103; BOTrsa: p = 0.474, ηp2 = 0.024). Children with low baseline balance performance (based on PBS) in the intervention group showed improvements in balance performance after training (PBS: p = 0.003, ηp2 = 0.304; BOTbal: p = 0.008, ηp2 = 0.258), whereas children with high baseline balance performance did not. CONCLUSIONS: This exergame-training resulted in balance improvements for the current population of CP that had a low baseline function.IMPLICATIONS FOR REHABILITATIONExergame-training (training using video-games) shows mixed results in children with cerebral palsy (CP).Children with spastic CP (GMFCS level I-II) with a high baseline balance-level did not show functional balance improvements after this home-based exergame-training, suggesting that these children should not be enrolled in this type of exergame-training protocol.Children with spastic CP (GMFCS level I-II) with a low baseline balance-level showed clinically relevant functional balance improvements after this home-based exergame-training, suggesting that these children can benefit from enrolment in this type of exergame-training protocol to improve their balance.The distribution of CP-symptoms did not affect the effectiveness of this balance exergame-training in children with spastic CP with GMFCS-level I and II.

VIRUSBreakend: Viral Integration Recognition Using Single Breakends.

MOTIVATION: Integration of viruses into infected host cell DNA can cause DNA damage and disrupt genes. Recent cost reductions and growth of whole genome sequencing has produced a wealth of data in which viral presence and integration detection is possible. While key research and clinically relevant insights can be uncovered, existing software has not achieved widespread adoption, limited in part due to high computational costs, the inability to detect a wide range of viruses, as well as precision and sensitivity. RESULTS: Here, we describe VIRUSBreakend, a high-speed tool that identifies viral DNA presence and genomic integration. It utilizes single breakends, breakpoints in which only one side can be unambiguously placed, in a novel virus-centric variant calling and assembly approach to identify viral integrations with high sensitivity and a near-zero false discovery rate. VIRUSBreakend detects viral integrations anywhere in the host genome including regions such as centromeres and telomeres unable to be called by existing tools. Applying VIRUSBreakend to a large metastatic cancer cohort, we demonstrate that it can reliably detect clinically relevant viral presence and integration including HPV, HBV, MCPyV, EBV and HHV-8. AVAILABILITY AND IMPLEMENTATION: VIRUSBreakend is part of the Genomic Rearrangement IDentification Software Suite (GRIDSS). It is available under a GPLv3 license from https://github.com/PapenfussLab/VIRUSBreakend. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Graduates of the Model Study Courses in the Health Professions in North Rhine-Westphalia: Employment Characteristics and Competencies in Professional Practice]. / Verbleib der Absolventinnen und Absolventen der Modellstudiengänge in den Gesundheitsfachberufen in Nordrhein-Westfalen: Ergebnisse zu Beschäftigungsmerkmalen und Kompetenzen in der Berufspraxis.

AIM: The aim of this article was to present key results of the graduates' survey VAMOS. The study examined the professional status of the graduates of 12 model study courses in the health professions in North Rhine-Westphalia. The focus of the article was on the employment characteristics of the current main jobs and the application of the academic competencies in everyday professional life. METHODS: In the early summer of 2018 (April to June), 515 graduates of the model study courses in nursing (N=244), physiotherapy (N=97), speech therapy (N=95), occupational therapy (N=47), and midwifery (N=32) were included in an online cross-sectional survey. Graduating classes between the winter semester 2013/2014 and the summer semester 2017 were included. In addition, employers (N=109) were interviewed who hired graduates from the model study courses. RESULTS: The main jobs of the graduates were mostly located in hospitals and outpatient therapy practices. Eight out of ten graduates (84%) performed tasks in direct contact with patients as the main part of their employment. In 71% of these cases, the regular tasks were combined with extended activities in comparison to colleagues without an academic degree. On average, the graduates felt confident in all competency dimensions examined in this study. In all dimensions, employers perceived a "competence advantage" for graduates compared to colleagues without an academic degree. CONCLUSION: The results of this graduate survey support the current recommendation to have the study programs in the five health care professions governed by professional laws and to enable the programs to be carried out at universities.

The head-to-head photodimer of indeno-indene.

Irradiation of 1-(1-benzo-cyclo-butenyl-idene)benzo-cyclo-butene gives indeno-indene and its head-to-head photodimer nona-cyclo-[9.7.7.72,10.01,11.02,10.03,8.012,17.019,24.026,31]dotriaconta-3,5,7,12,14,16,19,21,23,26,28,30-dodeca-ene, C32H24. The mol-ecule is built from four essentially planar indane units attached to an elongated cyclo-butane ring. In the crystal, C-H⋯π inter-actions connect mol-ecules into layers parallel to the bc plane.