Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks.

BACKGROUND: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE. METHODS: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses. RESULTS: We found that 196, 115, and 74 metabolites were associated (P<0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD. CONCLUSIONS: While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds.

Influence of Sphericity on Surface Termination of Icosahedral Colloidal Clusters.

Colloids self-organize into icosahedral clusters composed of a Mackay core and an anti-Mackay shell under spherical confinement to minimize the free energy. This study explores the variation of surface arrangements of colloids in icosahedral clusters, focusing on the determining factors behind the surface arrangement. To efficiently assemble particles in emulsion droplets, droplet-to-droplet osmotic extraction from particle-laden droplets to salt-containing droplets is used, where the droplets are microfluidically prepared to guarantee a high size uniformity. The icosahedral clusters are optimally produced during a 24-h consolidation period at a 0.04 m salt concentration. The findings reveal an increase in the number of particle layers from 10 to 15 in the icosahedral clusters as the average number of particles increases from 3300 to 11 000. Intriguingly, the number of layers in the anti-Mackay shells, or surface termination, appears to more strongly depend on the sphericity of the clusters than on the deviation in the particle count from an ideal icosahedral cluster. This result suggests that the sphericity of the outermost layer, formed by the late-stage rearrangement of particles to form an anti-Mackay shell near the droplet interface, may play a pivotal role in determining the surface morphology to accommodate a spherical interface.

Optimization of DNA extraction and sampling methods for successful forensic microbiome analyses of the skin and saliva.

Microbiome studies have contributed to many fields, such as healthcare and medicine; however, these studies are relatively limited in forensics. Microbiome analyses can provide information, such as geolocation and ancestry information, when short tandem repeat (STR) profiling fails. In this study, methods for DNA extraction and sampling from the skin and saliva were optimized for the construction of a Korean Forensic Microbiome Database (KFMD). DNA yields were estimated using four DNA extraction kits, including two automated kits (Maxwell® FSC DNA IQ™ Casework Kit and PrepFiler™ Forensic DNA Extraction Kit, updated) and two manual kits (QIAamp DNA Mini Kit and QIAamp DNA Micro Kit) commonly used in forensic DNA profiling laboratories. Next-generation sequencing of the 16S rRNA V4 region was performed to analyze microbial communities in samples. The Bacterial Transport Swab with Liquid Media (NobleBio), two cotton swabs (PoongSung and Puritan), and nylon-flocked swabs (NobleBio and COPAN) were tested for DNA recovery. The PrepFiler and Maxwell kits showed the highest yields of 3.884 ng/µL and 23.767 ng/µL from the scalp and saliva, respectively. With respect to DNA recovery, nylon-flocked swabs performed better than cotton swabs. The relative abundances of taxa sorted by DNA extraction kits were similar contributions; however, with significant differences in community composition between scalp and saliva samples. Lawsonella and Veillonella were the most abundant genera in the two sample types. Thus, the Maxwell® FSC DNA IQ™ Casework Kit and nylon-flocked swab (NobleBio) were optimal for DNA extraction and collection in microbiome analyses.

Parent meal self-efficacy and practices in households with healthy home food environments in the face of economic hardship.

Some families who experience economic hardship demonstrate remarkable strength and resourcefulness to sustain a healthy home food environment. This ability to navigate economic barriers could be associated with parent meal practices that promote children's healthful dietary intake. Therefore, this study aimed to examine 1) whether parent meal self-efficacy and practices were associated with economic assistance status and home fruit and vegetable (FV) availability and 2) how parent meal self-efficacy and practices differed by home FV availability and economic assistance status. Analyses utilized baseline data from 274 parent/child dyads from two childhood obesity prevention trials: HOME Plus (urban) and NU-HOME (rural). Parents in households with high FV availability (regardless of economic assistance) had significantly higher self-efficacy in preparing healthy foods, family dinner routines, frequency of child's plate being half filled with FV, frequency of family dinner and breakfast, and lower frequency of purchasing dinner from fast food restaurants. Economic assistance was not associated with parent meal self-efficacy and practices. Four family groups were created and defined by economic assistance (yes/no) and home FV availability (high/low). About 31% of families that received economic assistance and had high home FV availability were food insecure. Families (n = 39) receiving economic assistance and having high home FV availability had greater frequency of family dinners compared to those in households with economic assistance and low home FV availability (n = 47) (p = 0.001); no other parent meal self-efficacy or practices differed between groups. Our findings suggest some families can maintain healthy home food environments despite economic hardship and frequent family dinners may be an important strength for these families. More research is needed to investigate asset-based models to understand the family strengths that enable them to thrive during difficult times.

Beyond coping: The role of supportive relationships and meaning making in youth well-being.

INTRODUCTION: The purpose of this study was to identify coping strategies, resources, and strengths that predict well-being in a community-based sample of youth with varying levels of adversity. DESIGN: Grounded in the resilience portfolio model, we used a mixed methods approach with data from a cross-sectional sample of 231 youth ages 8-17. MATERIALS AND METHODS: Data were collected using a survey, participant-generated timeline activity, and brief interview. Measures included assessments of coping and appraisal, resilience resources and assets, and subjective well-being and depression. RESULTS: Active and passive coping strategies predicted subjective well-being and depression. Controlling for demographics and coping, meaning making strengths and supportive relationships were significant predictors of subjective well-being and lower depression, and decreased the impact of adversity on these outcomes. DISCUSSION: The results of this study provide support for the resilience portfolio model in a community-based sample of youth, with relationships as predicted for subjective well-being and symptoms of depression. For both outcomes, family relationships held the strongest associations with positive well-being and lower symptoms of depression. Supportive relationships with peers, meaning making strengths, interpersonal strengths, less passive coping, and fewer adverse life events were also associated with better outcomes. CONCLUSIONS: These findings underscore the need to assess youth resources and strengths and to design interventions that target these protective factors for all youth, regardless of exposure to adversity. CLINICAL RELEVANCE: A theory-informed understanding of resources and strengths that predict youth well-being is essential to inform strengths-based interventions for pediatric research and practice. The resilience portfolio model is a useful framework for understanding predictors of youth well-being.

Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of ß-catenin.

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/ß-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 µM) dose-dependently inhibited TOPFlash reporter activity and protein expression of ß-catenin, but not mRNA level of ß-catenin. Furthermore, celastrol accelerated the degradation of ß-catenin by promoting the formation of the ß-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/ß-catenin signaling by promoting the degradation of ß-catenin, consequently inhibiting the growth of VS.

Role of ripples in altering the electronic and chemical properties of graphene.

Ripples of graphene are known to manipulate electronic and hydrogenation properties of graphitic materials. More detailed work is needed to elucidate the structure-property relationship of these systems. In this work, the density functional theory is used to compute the energy and electronic structure of the graphene models with respect to variable curvatures and hydrogen adsorption sites. The magnitude of finite bandgap opening depends on the orientation of ripples, and the hydrogen adsorption energy depends on the local curvature of graphene. An adsorbed hydrogen alters the local curvature, resulting in relatively weakened adsorption on the neighboring three sites, which gives a rationale to experimentally observed dynamic equilibrium stoichiometry (H:C = 1:4) of hydrogenated graphene. The surface diffusion transition state energy of adsorbed hydrogen is computed, which suggests that the Eley-Rideal surface recombination mechanism may be important to establish the dynamic equilibrium, instead of the commonly assumed Langmuir-Hinshelwood mechanism.

Are patterns of family evening meal practices associated with child and parent diet quality and weight-related outcomes?

Family meal practices such as family member presence, fast food consumption and media usage have been associated with health outcomes. However, little is known about combinations of family meal practices and their effects on diet and health. This secondary data analysis aimed to identify patterns of family evening meal practices and examine their associations with family characteristics (e.g., demographics and chaos) and child and parent diet quality and weight-related outcomes. We used baseline data from a community-based randomized controlled trial with 7- to 10-year-old children and their parents in rural Minnesota (n = 114). Parent-reported structural (e.g. media usage) and interpersonal (e.g. mealtime routines) aspects of family evening meal practices were included in latent profile analyses to identify patterns. Diet quality was assessed by child Healthy Eating Index-2015 and parent fruit and vegetable intake. Weight-related outcomes were determined using measured body mass index (z-scores) and percent body fat. A 3-class model was the model of best-fit. The Unplanned Infrequent Family Evening Meals with Mixed Healthfulness class (C1) featured the least frequent family evening meals and the lowest scores for mealtime routines and planning skills. The Family Evening Meals with Fast Food class (C2) characterized having family evening meals four times a week, but fast food was often served. The Planful, Healthful and Frequent Family Evening Meals class (C3) reported the highest meal routine and planning scores as well as frequent family evening meals. Parents in C3 had higher consumption of fruits and vegetables and children in C3 had lower percent body fat, compared to those in other classes. Distinctly different patterns of family evening meal practices suggest a need for considering heterogeneity of family evening meal practices in developing tailored family-meal interventions.

Associations of parent dietary role modeling with children's diet quality in a rural setting: Baseline data from the NU-HOME study.

These analyses examined associations of parent dietary role modeling with diet quality among school-age children in a rural community. Past research has found protective associations between parent role modeling and children's dietary intake; however, there is a gap in understanding these associations for families in rural communities. Baseline data (2017 -2018) were drawn from the New Ulm at Home (NU-HOME) randomized controlled trial, conducted in the United States. The trial recruited 114 children (7-10 years old) and parents. Parents self-reported dietary intake [fruit and vegetable (FV), sugar-sweetened beverage (SSB), fast food (FF)] and frequency of sitting and eating with their child. Children reported parent role modeling of healthful eating (FV and salad at the evening meal; FV as snacks). Two 24-h dietary recalls assessed child diet quality indicators [Healthy Eating Index-2015 (HEI-2015) total scores, FV intake, SSB intake]. General linear models (GLM) and logistic regression analyzed associations of child diet quality (HEI score, FV intake, SSB intake) with parent dietary intake, parent sitting and eating the evening meal with their child, and child perceptions of parent role modeling healthful eating, adjusted for highest level of education in the home. Higher child HEI-2015 scores were positively associated with more frequent parent role modeling of fruit intake at meals, and inversely associated with more frequent parent role modeling of fruit as a snack; no significant associations of child FV intake with parent role modeling were observed. Higher child SSB intake was positively associated with parent FF intake. In this rural community, parents play significant roles in shaping children's dietary quality and intake, though more work needs to be done to address optimal intervention strategies to promote parent role modeling of healthful eating.

A reliable and robust method for the upper thigh muscle quantification on computed tomography: toward a quantitative biomarker for sarcopenia.

BACKGROUND: We aimed to evaluate the feasibility of the upper thigh level as a landmark to measure muscle area for sarcopenia assessment on computed tomography (CT). METHODS: In the 116 healthy subjects who performed CT scans covering from mid-abdomen to feet, the skeletal muscle area in the upper thigh level at the inferior tip of ischial tuberosity (SMAUT), the mid-thigh level (SMAMT), and L3 inferior endplate level (SMAL3) were measured by two independent readers. Pearson correlation coefficients between SMAUT, SMAMT, and SMAL3 were calculated. Inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman plots with 95% limit of agreement (LOA). RESULTS: In readers 1 and 2, very high positive correlations were observed between SMAUT and SMAMT (r = 0.91 and 0.92, respectively) and between SMAUT and SMAL3 (r = 0.90 and 0.91, respectively), while high positive correlation were observed between SMAMT and SMAL3 (r = 0.87 and 0.87, respectively). Based on ICC values, the inter-reader agreement was the best in the SMAUT (0.999), followed by the SMAL3 (0.990) and SMAMT (0.956). The 95% LOAs in the Bland-Altman plots indicated that the inter-reader agreement of the SMAUT (- 0.462 to 1.513) was the best, followed by the SMAL3 (- 9.949 to 7.636) and SMAMT (- 12.105 to 14.605). CONCLUSION: Muscle area measurement at the upper thigh level correlates well with those with the mid-thigh and L3 inferior endpoint level and shows the highest inter-reader agreement. Thus, the upper thigh level might be an excellent landmark enabling SMAUT as a reliable and robust biomarker for muscle area measurement for sarcopenia assessment.

Evolution of a Strategy for Concise Enantioselective Total Synthesis of the Salinosporamide Family of Natural Products.

Our first strategy for rapidly accessing pyrrolidinone cores of salinosporamides involved combined use of memory of chirality and dynamic kinetic resolution principles in aldol reactions of the serine-derived 5-oxazolidinone substrate, which was ultimately unsuccessful with respect to enantioselectivity. This failure led us to the revised strategy. The influence of the stereocenter in 5-oxazolidinone enabled selective installation of the C-2 stereocenter. The intramolecular aldol reaction of the C-2 stereodefined aldol substrate was successful. An unexpected hydrolytic dynamic kinetic resolution was observed in hydrolyses of the bicyclic aldol products. This unprecedented substrate-driven hydrolytic dynamic kinetic resolution was utilized in preparing the pyrrolidinone core with excellent efficiency. Through this strategy, the concise total syntheses of salinosporamides A and B as well as cinnabaramides A, E, and F were achieved with high selectivity.

Switching from insulin to dulaglutide therapy in patients with type 2 diabetes: A real-world data study.

AIM: Patients with type 2 diabetes (T2DM) who require injectable therapy have been conventionally treated with insulin. A glucagon-like peptide 1 receptor agonist was recently recommended as first-line injectable treatment, but few studies have investigated the effects of switching from insulin to dulaglutide. This study investigated the clinical efficacy and parameters affecting responses to dulaglutide as an alternative to insulin in patients with T2DM in a real-world clinical setting. METHODS: Ninety-eight patients with T2DM who were switched from insulin to dulaglutide therapy were retrospectively evaluated. Changes in HbA1c concentrations were assessed after 6 months of consistent treatment with dulaglutide. Multiple linear regression analysis was performed to evaluate parameters affecting the response to dulaglutide treatment. RESULTS: After treatment with dulaglutide for 6 months, patients experienced changes in HbA1c of -0.95% (95% confidence interval [CI]: -1.30% to -0.59%, P < 0.001) and in body weight of -1.75 kg (95% CI: -2.42 to -1.08 kg, P < 0.001). Multiple linear regression analysis showed that higher baseline HbA1c was significantly associated with a greater reduction in HbA1c. The most frequent adverse events were gastrointestinal symptoms. CONCLUSION: Switching from insulin to dulaglutide can lead to significant improvement in HbA1c levels and body weight ​reduction in T2DM patients over 6 months. Higher baseline HbA1c is associated with a better clinical response to dulaglutide.

Evaluation of extreme sub-daily precipitation in high-resolution global climate model simulations.

We examine the resolution dependence of errors in extreme sub-daily precipitation in available high-resolution climate models. We find that simulated extreme precipitation increases as horizontal resolution increases but that appropriately constructed model skill metrics do not significantly change. We find little evidence that simulated extreme winter or summer storm processes significantly improve with the resolution because the model performance changes identified are consistent with expectations from scale dependence arguments alone. We also discuss the implications of these scale-dependent limitations on the interpretation of simulated extreme precipitation. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

CDISC-compliant clinical trial imaging management system with automatic verification and data Transformation: Focusing on tumor response assessment data in clinical trials.

OBJECTIVE: Major issues in imaging data management of tumor response assessment in clinical trials include high human errors in data input and unstandardized data structures, warranting a new breakthrough IT solution. Thus, we aim to develop a Clinical Data Interchange Standards Consortium (CDISC)-compliant clinical trial imaging management system (CTIMS) with automatic verification and transformation modules for implementing the CDISC Study Data Tabulation Model (SDTM) in the tumor response assessment dataset of clinical trials. MATERIALS AND METHODS: In accordance with various CDISC standards guides and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, the overall system architecture of CDISC-compliant CTIMS was designed. Modules for standard-compliant electronic case report form (eCRF) to verify data conformance and transform into SDTM data format were developed by experts in diverse fields such as medical informatics, medical, and clinical trial. External validation of the CDISC-compliant CTIMS was performed by comparing it with our previous CTIMS based on real-world data and CDISC validation rules by Pinnacle 21 Community Software. RESULTS: The architecture of CDISC-compliant CTIMS included the standard-compliant eCRF module of RECIST, the automatic verification module of the input data, and the SDTM transformation module from the eCRF input data to the SDTM datasets based on CDISC Define-XML. This new system was incorporated into our previous CTIMS. External validation demonstrated that all 176 human input errors occurred in the previous CTIMS filtered by a new system yielding zero error and CDISC-compliant dataset. The verified eCRF input data were automatically transformed into the SDTM dataset, which satisfied the CDISC validation rules by Pinnacle 21 Community Software. CONCLUSIONS: To assure data consistency and high quality of the tumor response assessment data, our new CTIMS can minimize human input error by using standard-compliant eCRF with an automatic verification module and automatically transform the datasets into CDISC SDTM format.

Comparison of abdominal and minimally invasive radical hysterectomy in patients with early stage cervical cancer.

PURPOSE: The aim of this study was to compare survival outcomes of open radical hysterectomy and minimally invasive radical hysterectomy (MIS) in early stage cervical cancer. METHODS: A retrospective analysis of 148 patients with stage IB1 - IIA2 cervical cancer who underwent either minimally invasive or open radical hysterectomy. Tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS) were compared according to surgical approach. RESULTS: In total, 110 and 38 patients were assigned to open surgery and MIS groups. After a medical follow-up of 42.1 months, the groups showed similar survival outcomes (recurrence rate, DFS, and OS). However, in patients with tumor size >2 cm, recurrence rate was significantly higher in MIS group (22.5% vs 0%; p=0.008). And in patients with tumor size >2 cm, MIS group showed significantly poorer DFS than open surgery group (p=0.017), although OS was similar between the two groups (p=0.252). CONCLUSION: In patients with tumor size >2 cm, MIS was associated with higher recurrence rates and poorer DFS than open surgery. However, in patients with tumor size ≤2 cm, MIS did not seem to compromise oncologic outcomes.

Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods.

The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)-which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue-exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612.

Missed Work Among Caregivers of Children With a High Body Mass Index: Child, Parent, and Household Characteristics.

An underexamined consequence of childhood obesity is caregivers' missed work attributed to child absence from school due to a health condition. This secondary analysis (N = 123) reported the frequency of missed work among caregivers of children with a body mass index (BMI) at or above the 75th percentile and examined associations with select child, parent, and household characteristics. Caregivers missed work 1.3 (SD = 1.2) times in the past year with 41% reporting 2 or more times. A child visiting a health-care provider 2 or more times in the past year and parent perception of their child's health as good/fair/poor were significantly associated with caregivers' missing work 2 or more times in a year (OR = 5.8 and OR = 3.0, respectively). A significant association between children's physical and psychosocial well-being and caregivers' missed work emphasizes the school nurse role working with children with high BMI and families to address student absenteeism and caregivers' missed work.

The Association between Parents and Children Meeting Physical Activity Guidelines.

PURPOSE: To examine the association between parents and children meeting physical activity (PA) guidelines, by gender, among 8-12 year old children with BMI ≥75th percentile DESIGN AND METHODS: This was a secondary analysis of baseline data from a school-based healthy weight management intervention in Minnesota for 8-12 year old children. Survey data about PA participation were collected from 2014 through 2018. Analyses entailed descriptive statistics and multivariate logistic regression controlling for child age, race/ethnicity, BMIz, child's perception of parent support for activity, and number of sports played. RESULTS: Children's (n = 132) mean age was 9.32 ± 0.89 years, 49% were female, 63% were members of racial/ethnic minority groups, and 33% met PA Guidelines (≥60 minutes daily). Parents' (n = 132) mean age was 39.11 ± 7.05 years, mean BMI of 30.90 ± 8.44, 94% were female, 42% were members of racial/ethnic minority groups, and 57% met PA Guidelines for Americans (≥150 minutes moderate or >75 minutes vigorous PA weekly). There was no association between parents and children meeting PA guidelines for the total sample (OR = 1.43, 95% CI = 0.63-3.24, p = 0.39) or girls (OR = 0.65, 95% CI = 0.18-2.33, p = 0.51). Boys whose parents met PA guidelines had 3.84 times greater odds of meeting PA guidelines (95% CI = 1.28-13.4, p = 0.04). CONCLUSIONS: PA interventions for boys may benefit from focus on parents' PA. Further research should investigate correlates of girls' PA. PRACTICE IMPLICATIONS: Pediatric nurses working with children to increase PA should encourage parents' PA. For parents of boys, this may increase the child's PA. Considered broadly, nurses should be aware of gender influences on children's engagement in PA.

ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment.

Glucagon-like peptide-1 (GLP-1) is a well-known incretin hormone secreted from enteroendocrinal L cells in response to nutrients, such as glucose and dietary fat, and controls glycemic homeostasis. However, the detailed intracellular mechanisms of how L cells control GLP-1 secretion in response to nutrients still remain unclear. Here, we report that bone morphogenetic protein (BMP) signaling pathway plays a pivotal role to control GLP-1 secretion in response to nutrient replenishment in well-established mouse enteroendocrinal L cells (GLUTag cells). Nutrient starvation dramatically reduced cellular respiration and GLP-1 secretion in GLUTag cells. Transcriptome analysis revealed that nutrient starvation remarkably reduced gene expressions involved in BMP signaling pathway, whereas nutrient replenishment rescued BMP signaling to potentiate GLP-1 secretion. Transient knockdown of inhibitor of DNA binding (ID)1, a well-known target gene of BMP signaling, remarkably reduced GLP-1 secretion. Consistently, LDN193189, an inhibitor of BMP signaling, markedly reduced GLP-1 secretion in L cells. In contrast, BMP4 treatment activated BMP signaling pathway and potentiated GLP-1 secretion in response to nutrient replenishment. Altogether, we demonstrated that BMP signaling pathway is a novel molecular mechanism to control GLP-1 secretion in response to cellular nutrient status. Selective activation of BMP signaling would be a potent therapeutic strategy to stimulate GLP-1 secretion in order to restore glycemic homeostasis.

The Identification of Family Social Environment Typologies Using Latent Class Analysis: Implications for Future Family-Focused Research.

The family social environment is the first environment that a child experiences and has implications for children's health. However, the majority of family social environment measures do not account for its complexity. There is a need for novel approaches for assessing the family social environment that transcends the traditional way of measuring family composition and interaction. The purpose of this secondary data analysis research was to identify distinct family social environment typologies that consider both family composition and interaction and to describe the characteristics of the identified family social environment typologies. A series of latent class analysis results indicated three distinct typologies of family social environment with significant differences in family composition, family problem-solving skills, and demographic characteristics. The process used to identify the typologies and significant differences between the typologies showcases how the field could advance family-focused research by considering family composition and interaction.