Phase separation of multicomponent peptide mixtures into dehydrated clusters with hydrophilic cores.

Phase separation of biomolecules underlies the formation and regulation of various membraneless condensates in cells. How condensates function reliably while surrounded by heterogeneous and dynamic mixtures of biomolecular components with specific and nonspecific interactions is yet to be understood. Studying multicomponent biomolecular mixtures with designer peptides has recently become an attractive avenue for learning about physicochemical principles governing cellular condensates. In this work, we employed long-timescale atomistic simulations of multicomponent tripeptide mixtures with all residue substitutions to illuminate the nature of direct and water-mediated interactions in a prototypical cellular condensate environment. We find that peptide mixtures form clusters with inverse hydrophobic order. Most multivalent and charged residues are localized in the cluster's core, with a large fraction of nonaromatic hydrophobic residues remaining on the surface. This inverse hydrophobic order in peptide clusters is partly driven by the expulsion of nonspecifically bound water molecules following peptide cluster growth. The growth of clusters is also accompanied by the formation of increasing numbers of specific water-mediated interactions between polar and charged residues. While the present study focused on the condensation of short peptide motifs, the general findings and analysis techniques should be helpful for future studies on larger peptides and protein condensation.

Linking Activity, Nutrition, and Child Health (LAUNCH): protocol for a longitudinal cohort study of children as they develop from infancy to preschool age.

BACKGROUND: Physical activity is known to provide important health benefits in children ages 3 years and above, but little is known about the effects of physical activity on health in very young children under age 3. LAUNCH (Linking Activity, Nutrition, and Child Health) is a study designed to expand the body of knowledge on development of physical activity behavior and associations between physical activity and other health characteristics as children transition from infancy to preschool age. METHODS: Physical activity and sedentary behavior will be measured objectively in young children over a period of 30 months. Each child will complete a measurement protocol at 6, 12, 18, 24, 30 and 36 months of age. The following factors will be measured at each time point: physical activity, sedentary behavior, anthropometric characteristics, and motor developmental status. Objectively-measured sleep behavior will be included as an optional component of the protocol. Parents will provide information on demographic factors, parenting behaviors, home and childcare characteristics, and the child's dietary and sleep behaviors. DISCUSSION: LAUNCH will employ a longitudinal study design and objective measures of physical activity, sedentary behavior and sleep in examining developmental trends for those characteristics in children between the ages of 6 and 36 months. Associations among physical activity, sedentary behavior, sleep, and weight status will be examined. Findings will inform public health guidance and intervention strategies for very young children.

Study of Health and Activity in Preschool Environments (SHAPES): study protocol for a randomized trial evaluating a multi-component physical activity intervention in preschool children.

BACKGROUND: Physical inactivity is a recognized public health concern. Inadequate proportions of children in the U.S, including those of preschool age, are meeting physical activity recommendations. In response to low numbers of preschool children attaining appropriate physical activity levels, combined with the large number of young children who attend preschool, researchers have identified the need to devise interventions to increase physical activity at preschools. However, few multi-component interventions to increase physical activity in preschool children exist. The aims of this study were to observe the effects of a multi-component intervention on physical activity, sedentary behavior, and physical activity energy expenditure in 3-5 year-old children; identify factors that associate with change in those variables; and evaluate the process of implementing the multi-component intervention. The purpose of this manuscript is to describe the study design and intervention protocol. METHODS/DESIGN: The overall design of the Study of Health and Activity in Preschool Environments (SHAPES) was a two-year randomized trial (nested cohort design), with two conditions, two measurement occasions, and preschool serving as the unit of analysis. Sixteen schools (eight intervention and eight control) were enrolled. The intervention protocol was based on the social ecological model and included four main components: (a) indoor physical activity ("move inside"), (b) recess ("move outside"), (c) daily lessons ("move to learn"), and (d) social environment. Components were implemented using teacher and administrator trainings and workshops, site support visits, newsletters, and self-monitoring methods. Outcomes included accelerometer assessment of physical activity, sedentary behavior, and physical activity energy expenditure; weight status; and demographic factors; family/home social and physical environment; and parental characteristics. An extensive process evaluation battery was also used to monitor dose delivered by interventionists, completeness of intervention component delivery by teachers, and fidelity of teachers' implementation. DISCUSSION: The study will address important gaps relative to increasing physical activity in preschool children. Few studies to date have incorporated a multi-component approach, rigorous measurement protocol, and thorough evaluation of intervention implementation.

An observation system to assess physical activity of children with developmental disabilities and delays in preschool.

BACKGROUND: Physical activity (PA) behaviors during preschool settings can influence the health and development of children with developmental disabilities (DD). There is a need for a direct observation system that simultaneously assesses PA and preschool environmental contexts. OBJECTIVE: The purpose of this study was to develop an observation instrument for measuring PA and related contextual factors of preschoolers with DD, and to establish content validity and reliability. METHODS: Content validity was established through consultation with experts, informal observations in inclusive and special education preschools, and literature reviews. Categories and codes were identified and modified from existing observational systems for young children. Reliability was assessed in a convenience sample of preschool children with DD using a cross-sectional design. Data were collected using a momentary time sampling system (5-sec observe, 25-sec record) following a focal child. Inter-rater reliability was assessed during 20% of the observation sessions. RESULTS: The instrument development process resulted in ten coding categories that accounted for PA levels, types, and social and physical environmental contexts relevant to preschoolers with disabilities. Observers completed 137.5 observation sessions, yielding 5498 30-s observation intervals. Interval-by-interval percent agreement was excellent (91%-100%) and kappa values were high (0.82-0.99). CONCLUSIONS: The instrument was found to be a reliable measure of PA of preschoolers with DD and provided important contextual information about PA behaviors in early childhood special education settings. Additionally, it allowed for the simultaneous measurement of specific types and contexts of PA behaviors of preschoolers with DD and will be useful for describing PA and informing future interventions.

Preschool Environmental Influences on Physical Activity in Children with Disabilities.

PURPOSE: The purpose of this study was to describe associations between physical and social environmental features of preschools and physical activity behaviors of young children with developmental disabilities. METHODS: A sample of 34 preschool-age children (mean age, 4.28 ± 1.07; male, 64.7%) with developmental disabilities participated in this study. Physical activity and preschool environmental factors were measured through direct observation using the Observational System for Recording Physical Activity in Children-Developmental Disabilities version. Children were observed approximately eight times over the course of a week, yielding a total of 11, 310 observation intervals. The number of intervals and percentage of time spent in physical activity across environmental contexts were calculated. Logistic regression analyses were conducted to determine associations between time spent in physical activity and features of the physical and social environment. RESULTS: Children with disabilities were sedentary for most of the observed intervals (81.5%). Children were 4.8 times (confidence interval (CI), 4.25-5.50) more likely to be physically active while outdoors compared with indoors. Physical activity was more likely to occur in open spaces (odds ratio [OR], 3.3; CI, 2.59-4.19) and when using portable play equipment (OR, 2.7; CI, 1.31-5.64) compared with fixed playground equipment. While indoors, children in this study were 5.6 times (CI, 3.78-8.03) more likely to be active when in therapy compared with group time activities. Physical activity was more likely to occur when in solitary (OR, 3.4; CI, 2.87-4.10) or one-on-one group contexts (OR, 1.7-2.9) compared with in groups with an adult present. CONCLUSIONS: Certain features of the preschool setting, such as location and social group composition, were more conducive to physical activity than others. Children with disabilities would benefit from more time outdoors and in smaller group settings during preschool.

Social and environmental factors associated with preschoolers' nonsedentary physical activity.

The twofold purposes of the investigation were (a) to describe with direct observation data the physical activity behaviors and the accompanying social and environmental events of those behaviors for children in preschools and (b) to determine which contextual conditions were predictors of moderate to vigorous physical activity (MVPA) and nonsedentary physical activity (i.e., light activity + MVPA) for 3-, 4-, and 5-year-old children during their outdoor play. The results indicate that preschoolers' physical activity is characterized as sedentary in nature throughout their preschool day (i.e., 89% sedentary, 8% light activity, and 3% MVPA). During outdoor play periods, when children are most likely to be physically active, some contextual and social circumstances better predict their physical activity. Implications for policy makers, practitioners, and researchers are discussed.

Childcare Center Characteristics Moderate the Effects of a Physical Activity Intervention.

Center-based early childhood education and care (ECEC) programs are well-positioned to create positive impacts on the health and development of large numbers of young children by promoting physical activity using evidence-based programs. Studies testing physical activity programs for young children should examine the circumstances under which programs are most effective by assessing the role of contextual factors on program outcomes. The purpose of this study was to examine the moderating effects of baseline ECEC center characteristics on the relationship between the Study of Health and Activity in Preschool Environments (SHAPES) intervention and moderate-to-vigorous physical activity (MVPA). MVPA was assessed via accelerometry; center characteristics, practices, and social and physical environments were assessed by director interview and observation; and center quality was assessed using the Early Childhood Environment Rating Scale-Revised Edition. Mixed-model analyses of covariance (ANCOVAs) examined intervention effects on MVPA during the school day; interactions between baseline center variables and group assignment (intervention vs. control) tested for moderation. Two center instructional practices, two social environment characteristics, and one physical environment characteristic at baseline moderated the effects of SHAPES on MVPA outcomes. Assessing baseline practices and center characteristics may aid efforts to match centers with interventions likely to increase physical activity as well as suggest additional intervention strategies to test.

The translation of an evidence-based preschool physical activity intervention from in-person to online delivery of professional development to preschool teachers.

Study of Health and Activity in Preschool Environments (SHAPES) aimed to increase preschoolers' physical activity by engaging preschool teachers in professional development designed to modify instructional practices. SHAPES originated as a randomized controlled trial, tested in 16 preschools and disseminated to 4 control schools, and was shown to be effective in increasing preschool children's physical activity (Phase I, 2008-2012). This article describes the steps taken to translate an evidence-based physical activity intervention, SHAPES, from in-person delivery to online delivery of professional development to preschool teachers. In Phase II (2013-2016), professional development delivery was modified from an in-person to an online program for preschool teachers. Teacher implementation completeness and fidelity were examined in 10 pilot preschools and then replicated in 30 preschools. Large-scale dissemination of SHAPES began in Phase III (2017-2019), reaching 818 teachers from 228 unique centers after 2 years. The final SHAPES program consisted of six online modules, an accompanying guidebook, over 90 activities, self-assessment techniques, a video library, and an electronic community forum. The SHAPES core elements, defined in Phase I, were retained throughout all three phases. The Phase II change to online delivery was characterized by high levels of implementation completeness and fidelity. Results of Phase III statewide dissemination revealed comparable implementation completeness and fidelity. An intervention shown to be effective in a randomized controlled trial can be translated into an online professional development program and disseminated on a large scale in a timely manner.

Evaluating and Refining the Conceptual Model Used in the Study of Health and Activity in Preschool Environments (SHAPES) Intervention.

This study investigated the utility of the Study of Health and Activity in Preschool Environments (SHAPES) conceptual model, which targeted physical activity (PA) behavior in preschool children, by examining the relationship between implementation monitoring data and child PA during the school day. We monitored implementation completeness and fidelity based on multiple elements identified in the conceptual model. Comparing high-implementing, low-implementing, and control groups revealed no association between implementation and outcomes. We performed post hoc analyses, using process data, to refine our conceptual model's depiction of an effective preschool PA-promoting environment. Results suggest that a single component of the original four-component conceptual model, providing opportunities for moderate-to-vigorous physical activity through recess for 4-year-old children in preschool settings, may be a good starting place for increasing moderate-to-vigorous physical activity. Interventions that are implemented with optimal levels of completeness and fidelity are more likely to achieve behavior change if they are based on accurate conceptual models. Examining the mechanisms through which an intervention produces its effects, as articulated in the conceptual model that guides it, is particularly important for environmentally focused interventions because they are guided by emerging frameworks. The results of this study underscore the utility of using implementation monitoring data to examine the conceptual model on which the intervention is based.

Motor competence and characteristics within the preschool environment.

OBJECTIVES: Environmental characteristics within preschools that influence children's motor competence are largely unknown. The purpose of the present study was to examine the contribution of various preschool environmental characteristics to children's locomotor, object control, and total gross motor scores. DESIGN: Cross-sectional, observational study of 3-5 year-old children (n=229) from 22 preschools in South Carolina. METHODS: The Children's Activity and Movement in Preschool Study (CHAMPS) Motor Skills Protocol assessed MC. Preschool directors provided information regarding policies and practices. The research team measured playgrounds and classrooms, and the Early Childhood Environment Rating Scale-Revised assessed preschool quality. Time spent in open space and electronic media use were also assessed using direct observation. The aforementioned variables predicted children's object control, locomotor, and total gross motor scores. RESULTS: Classroom size/child ratio, teacher education, playground size, electronic media use, and trips to outside organizations emerged as significant predictors of locomotor score and total motor score. The object control model was non-significant. CONCLUSIONS: Preschools may be able to promote motor competence by allowing children more time in open spaces, structured activity experiences, and by expanding existing outdoor playground space whenever possible.

Development and Testing of the Observational System for Recording Physical Activity in Children: Elementary School.

PURPOSE: This study describes the development and pilot testing of the Observational System for Recording Physical Activity-Elementary School (OSRAC-E) Version. METHOD: This system was developed to observe and document the levels and types of physical activity and physical and social contexts of physical activity in elementary school students during the school day. Interobserver agreement scores and summary data were calculated. RESULTS: All categories had Kappa statistics greater than .80, with the exception of the activity initiator category. Interobserver agreement scores were 96% or greater. The OSRAC-E was shown to be a reliable observation system that allows researchers to assess physical activity behaviors, the contexts of those behaviors, and the effectiveness of physical activity interventions in the school environment. CONCLUSION: The OSRAC-E can yield data with high interobserver reliability and provide relatively extensive contextual information about the physical activity of students in elementary schools.

An Overview of the Evolution of Direct Cholangioscopy Techniques for Diagnosis and Therapy.

Direct examination of the biliary tree with endoscopes has been a challenge since endoscopists began performing endoscopic retrograde cholangiopancreatography (ERCP) in the late 1960s. Previously, surgeons had used rigid instruments intraoperatively, which made examination difficult. The first direct cholangioscopy performed by an endoscopist was likely unintentionally done in a patient with postsurgical anatomy. Indirect imaging, ERCP, and percutaneous transhepatic cholangiography are helpful modalities for examining the biliary tree, but they are limited procedures, particularly with regard to the evaluation and treatment of strictures and bile duct stones. This article reviews the history and evolution of direct cholangioscopy since the advent of flexible endoscopes. Additionally, the article describes a new single-operator cholan-gioscopy technique for direct visualization of the biliary tree for diagnosis and intervention. There remains opportunity for innovation as endoscopists strive for safe and less-invasive methods for the identification and treatment of biliary pathology.

Systematic dissemination of a preschool physical activity intervention to the control preschools.

For public health interventions to have a meaningful impact on public health, they must be disseminated to the wider population. Systematic planning and evaluation of dissemination efforts can aid translation from experimental trials to larger dissemination programs. The Study of Health and Activity in Preschool Environments (SHAPES) was a group-randomized intervention trial conducted in 16 preschools that successfully increased the physical activity of preschool age children. Following the completion of the research study protocol, the intervention was abbreviated, modified and implemented in four preschools that participated as control preschools in the original research study. The purposes of the current study were to describe the process of refining the intervention for dissemination to the control preschools, and to assess the acceptability of the resulting abbreviated intervention delivery. Five overarching behavioral objectives, informed by process evaluation, data from the original trial and collaboration with intervention teachers, were used to guide the implementation. Teachers in the dissemination classrooms reported high levels of acceptability, potential for sustainability of the program, and positive results in knowledge, skills, and child outcomes. Researchers can include a systematic approach to dissemination of effective intervention elements to the control participants in experimental studies to inform future dissemination efforts and begin to bridge the dissemination gap.

An Intervention to Increase Physical Activity in Children: A Randomized Controlled Trial With 4-Year-Olds in Preschools.

INTRODUCTION: A majority of preschool-aged children spend a significant portion of every weekday in a preschool or child care setting, where they typically participate in limited physical activity. This study determined if an ecologic physical activity intervention in preschools increases children's moderate- to vigorous-intensity physical activity (MVPA). DESIGN: RCT, with preschool as the unit of randomization and analysis. Child physical activity was measured by accelerometry. Mixed model analysis of covariance with preschool as a random variable was used to test the effects of the intervention on physical activity in the total group and in sex-specific subgroups. Data were collected in 2008-2010 and analyzed in 2012-2014. SETTING/PARTICIPANTS: Children in 4-year-olds' classrooms in 16 preschools, pair matched and assigned to intervention or control groups. INTERVENTION: The intervention focused on increasing children's physical activity by changing instructional practices. Researchers trained preschool teachers to engage children in physical activity during (1) structured, teacher-led physical activity opportunities in the classroom; (2) structured and unstructured physical activity opportunities at recess; and (3) physical activity integrated into pre-academic lessons. Research staff encouraged teachers to adapt the intervention to their classrooms. MAIN OUTCOME MEASURES: Minutes/hour of MVPA during the preschool day. RESULTS: In an analytic sample of 379 children (188 intervention, 191 control), those in the intervention schools engaged in significantly more MVPA than children in control schools (7.4 and 6.6 minutes/hour, respectively). This difference remained significant after adjusting for parent education and length of the school day (half versus full day). In the sex-specific analyses, the difference was significant for girls (6.8 vs 6.1 minutes/hour of MVPA, respectively) but not for boys (7.9 vs 7.2 minutes/hour, respectively). CONCLUSIONS: A flexible ecologic physical activity intervention that trains teachers to provide children with opportunities to be active throughout the school day increased MVPA in preschool children.

Development of a rapid autopsy program for studies of brain immunity.

Human glia are essential cellular models used for studies of neurodegenerative diseases. Fetal neuroglia are commonly used, as they can be recovered in large quantities and sustained for long periods in culture. However, fetal neuroglia may have limitations in reflecting adult diseases and additionally can pose ethical issues in translating products of abortion for research use. To address these concerns, we developed a rapid autopsy program to procure age- and disease-specific neuroglia from adult brain tissues within hours of death. The challenges in developing this initiative, reflecting experiences from 69 autopsies over 4 years, are presented.

Autoimmune Pancreatitis: A Multiorgan Disease Presenting a Conundrum for Clinicians in the West.

Autoimmune pancreatitis (AIP), a clinical entity originally described in East Asia and more recently recognized in the United States and Europe, poses a diagnostic conundrum for clinicians in the West due to immunoglobulin G4 seronegativity. Although expert panels classify this disease into 2 types, it remains difficult to stratify the disease given that both types share most clinical, biochemical, and imaging characteristics. The classic presentation of AIP can mimic that of pancreatic carcinoma, which increases the urgency of evaluation, diagnosis, and treatment. In this article, we elucidate the differences between the 2 types of AIP, highlight the shortcomings of the current classification system, and propose a more inclusive view of the disorder.

Prevalence of Compliance with a New Physical Activity Guideline for Preschool-Age Children.

BACKGROUND: Four expert panels from Australia, Canada, the United Kingdom, and the United States issued physical activity (PA) recommendations for young children that are quite similar. The aim of this study was to determine compliance with the new PA guideline (defined as ≥15 min/hr of total PA) in two independent samples of preschool children. METHODS: We conducted a cross-sectional study of children attending preschools in Columbia, South Carolina. A total of 286 children in one sample and 337 children in a second sample participated. The main outcome of interest was total PA (sum of light, moderate, and vigorous intensity activity) measured by accelerometry. Compliance with the PA guideline was determined for both samples. Separately for each sample, mixed logistic models were used to determine whether there were differences in compliance with the PA guideline between groups based on sex, race/ethnicity, parent education, and weight status, controlling for preschool. RESULTS: Total PA was 14.5 and 15.2 min/hr in the first and second samples, respectively. The prevalence of meeting the PA guideline was 41.6% and 50.2% in the first and second samples, respectively. In both samples, more males than females met the guideline (53.5% vs. 33.5% and 57.6% vs. 45.9%) in the first and second samples, respectively (p<0.05). CONCLUSIONS: Approximately one half of children in two independent samples met the guideline for PA in young children. Policies and practices designed to increase PA among preschool children are needed, given that most children are not meeting this PA guideline.

Young children's motor skill performance: relationships with activity types and parent perception of athletic competence.

OBJECTIVES: The aims were to examine the relationship between children's motor skill levels and types of physical activities performed during preschool attendance, and to examine the relationship between motor skill performance and parent perception of athletic competence. DESIGN: Cross-sectional. METHODS: Participants were 264, 3-, 4-, and 5-year-old children from 22 preschools. Locomotor and object control skills were assessed with a standardized motor skill protocol. Direct observation (OSRAC-P) was used to record activity types: walk, run, jump/skip, dance, and throw. Parents rated their child's athletic competence. Children were categorized into tertiles for locomotor and object control scores. Mixed models were used to test for differences across motor skill tertiles for each aim. Models controlled for sex, age, race/ethnicity, body mass index, and parent education, with preschool as a random variable. RESULTS: Children in the highest locomotor tertile engaged in more dancing than children in the lowest tertile (p = 0.04). Children in the highest object control tertile engaged in throwing more frequently than children in lower tertiles (p < 0.05). Parents of children in the highest locomotor tertile perceived their children's competence as higher than parents of children in lower tertiles (p < 0.05). Parents of children in the lowest object control tertile perceived their children's competence as significantly lower than parents of children in higher tertiles (p < 0.05). CONCLUSIONS: These findings point to the need for policy and practice research to help parents and child care professionals provide opportunities for young children to learn and practice motor skills.

Physical activity in preschool children: comparison between Montessori and traditional preschools.

BACKGROUND: Little is known about the influence of Montessori methods on children's physical activity (PA). This cross-sectional study compared PA of children attending Montessori and traditional preschools. METHODS: We enrolled 301 children in 9 Montessori and 8 traditional preschools in Columbia, South Carolina. PA was measured by accelerometry on weekdays during preschool (In-School), non-school (Non-School), and all day (All Day). Minutes/hour of light, moderate-to-vigorous (MVPA), and total PA (light + MVPA) were calculated. RESULTS: Children attending Montessori preschools accumulated more In-School light (7.7 vs. 6.5 minute/hour), MVPA (7.7 versus 6.5 minute/hour), and total PA (15.4 versus 13.0 minute/hour) than children attending traditional preschools, after adjusting for sex, race/ethnicity, body mass index, parent education and neighborhood poverty index. For Non-School (8.5 versus 6.2 minute/hour) and All Day (8.5 versus 7.6 minute/hour), children in Montessori preschools accumulated more MVPA than children in traditional preschools. In-School PA was higher for children in private Montessori than public Montessori preschools (8.1 versus 7.0 minute/hour; 8.1 versus 6.7 minute/hour; 16.1 versus 13.6 minute/hour, for light, MVPA, and total PA, respectively). CONCLUSIONS: Children attending Montessori preschools were more active than children attending traditional preschools. Adopting the Montessori system may be an important strategy for promoting PA in children.