Nutrition and physical activity randomized control trial in child care centers improves knowledge, policies, and children’s body mass index

Background To address the public health crisis of overweight and obese preschool-age children, the Nutrition And Physical Activity Self Assessment for Child Care (NAP SACC) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge, center-level nutrition and physical activity policies and practices, and children’s body mass index (BMI). Methods A seven-month randomized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California, Connecticut, and North Carolina, including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old. The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants. Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents. Blinded research assistants reviewed each center’s written health and safety policies, observed nutrition and physical activity practices, and measured randomly selected children’s nutritional intake, physical activity, and height and weight pre- and post-intervention. Results Hierarchical linear models and multiple regression models assessed individual- and center-level changes in knowledge, policies, practices and age- and sex-specific standardized body mass index (zBMI), controlling for state, parent education, and poverty level. Results showed significant increases in providers’ and parents’ knowledge of nutrition and physical activity, center-level improvements in policies, and child-level changes in children’s zBMI based on 209 children in the intervention and control centers at both pre- and post-intervention time points. Conclusions The NAP SACC intervention, as delivered by trained child health professionals such as child care health consultants, increases provider knowledge, improves center policies, and lowers BMI for children in child care centers. More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic. Trial registration National Clinical Trials Number NCT0192184

Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts

Competition for nutrients contained in diverse types of plant cell wall-associated polysaccharides may explain the evolution of substrate-specific catabolic gene modules in common bacterial members of the human gut microbiota

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

A method to determine spatial access to specialized palliative care services using GIS

Background: Providing palliative care is a growing priority for health service administratorsworldwide as the populations of many nations continue to age rapidly. In many countries, palliativecare services are presently inadequate and this problem will be exacerbated in the coming years.The provision of palliative care, moreover, has been piecemeal in many jurisdictions and there islittle distinction made at present between levels of service provision. There is a pressing need todetermine which populations do not enjoy access to specialized palliative care services in particular.Methods: Catchments around existing specialized palliative care services in the Canadian provinceof British Columbia were calculated based on real road travel time. Census block face populationcounts were linked to postal codes associated with road segments in order to determine thepercentage of the total population more than one hour road travel time from specialized palliativecare.Results: Whilst 81% of the province\u27s population resides within one hour from at least onespecialized palliative care service, spatial access varies greatly by regional health authority. Based onthe definition of specialized palliative care adopted for the study, the Northern Health Authorityhas, for instance, just two such service locations, and well over half of its population do not havereasonable spatial access to such care.Conclusion: Strategic location analysis methods must be developed and used to accurately locatefuture palliative services in order to provide spatial access to the greatest number of people, andto ensure that limited health resources are allocated wisely. Improved spatial access has thepotential to reduce travel-times for patients, for palliative care workers making home visits, and fortravelling practitioners. These methods are particularly useful for health service planners – andprovide a means to rationalize their decision-making. Moreover, they are extendable to a numberof health service allocation problems

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies