Impact of a Summer Nutrition and Physical Activity Intervention to Attenuate Obesity in Urban African-American Youth

Improved eating behaviors and daily participation in physical activity such as swimming might abate the likelihood of African American youth becoming obese. Yet many African American youth neither consume the recommended daily servings of nutritious foods nor know how to swim. The purpose of this study was to investigate the impact of a culturally tailored multicomponent summer intervention to reduce obesity and unintentional drownings among underserved African American youth. Children (n = 145) participated in a three-hour, community-based intervention for four weeks. Measures of children’s attitudes perceived behavioral control, and subjective norms toward swimming, nutrition, and physical fitness were taken at baseline and 4 weeks later (n = 47). The only post-intervention significant finding indicated an improvement in children’s skillfulness in floating on their back without help. The limited changes in this multi-component program suggested that such interventions need to be longer in duration, intensity, and be required to reduce attrition

Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis

The pill questionnaire in a nondemented Parkinson's disease population

We assessed the Pill Questionnaire as a screen for mild cognitive impairment in nondemented Parkinson's disease patients. The relationship between ability to remember medications for Parkinson's disease in the Pill Questionnaire, mild cognitive impairment, and deficits on neuropsychological tests performed 2–3 weeks later blind to Pill Questionnaire results was assessed in movement disorders clinic patients. In 109 subjects, inaccurate medication reporting on the Pill Questionnaire was associated with lower scores on the Montreal Cognitive Assessment, Scales for Outcomes in Parkinson's Disease–Cognition and with deficits in memory, attention, executive function‐inhibitory control, processing speed, visuospatial function, and language. Inaccurate medication reporting was also associated with an adjusted odds ratio of 2.4 (95% CI, 0.91–5.88; P = .06) for mild cognitive impairment, with a specificity of 80% and sensitivity of 41%. The Pill Questionnaire is neither sensitive nor specific enough to be used as the sole screening or diagnostic tool for mild cognitive impairment. However, inaccurate medication reporting is associated with deficits spanning many cognitive domains and should alert a clinician to a higher likelihood of cognitive impairment. © 2012 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93736/1/25124_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93736/2/MDS_25124_sm_SuppTables.pd

Anatomy of a Dansgaard-Oeschger warming transition: High-resolution analysis of the North Greenland Ice Core Project ice core

Large and abrupt temperature oscillations during the last glacial period, known as Dansgaard‐Oeschger (DO) events, are clearly observed in the Greenland ice core record. Here we present a new high‐resolution chemical (2 mm) and stable isotope (20 mm) record from the North Greenland Ice Core Project (NGRIP) ice core at the onset of one of the most prominent DO events of the last glacial, DO‐8, observed ∼38,000 years ago. The unique, subannual‐resolution NGRIP record provides a true sequence of change during a DO warming with detailed annual layer counting of very high depth resolution geochemical measurements used to determine the exact duration of the transition. The continental ions, indicative of long‐range atmospheric loading and dustiness from East Asia, are the first to change, followed by the snow accumulation, the moisture source conditions, and finally the atmospheric temperature in Greenland. The sequence of events shows that atmospheric and oceanic source and circulation changes preceded the DO warming by several years

Aging is associated with a prefrontal lateral-medial shift during picture-induced negative affect

The capacity to adaptively respond to negative emotion is in part dependent upon lateral areas of the prefrontal cortex (PFC). Lateral PFC areas are particularly susceptible to age-related atrophy, which affects executive function (EF). We used structural and functional magnetic resonance imaging (MRI) to test the hypothesis that older age is associated with greater medial PFC engagement during processing of negative information, and that this engagement is dependent upon the integrity of grey matter structure in lateral PFC as well as EF. Participants (n = 64, 38–79 years) viewed negative and neutral scenes while in the scanner, and completed cognitive tests as part of a larger study. Grey matter probability (GMP) was computed to index grey matter integrity. FMRI data demonstrated less activity in the left ventrolateral PFC (VLPFC) and greater ventromedial PFC (VMPFC) activity with increasing age during negative-picture viewing. Age did not correlate with amygdala responding. GMP in VLPFC and EF were negatively associated with VMPFC activity. We conclude that this change from lateral to medial PFC engagement in response to picture-induced negative affect reflects decreased reliance on executive function-related processes, possibly associated with reduced grey matter in lateral PFC, with advancing age to maintain emotional functioning

A Recombinant Vaccine Effectively Induces C5a-Specific Neutralizing Antibodies and Prevents Arthritis

OBJECTIVES: To develop and validate a recombinant vaccine to attenuate inflammation in arthritis by sustained neutralization of the anaphylatoxin C5a. METHODS: We constructed and expressed fusion protein of C5a and maltose binding protein. Efficacy of specific C5a neutralization was tested using the fusion protein as vaccine in three different arthritis mouse models: collagen induced arthritis (CIA), chronic relapsing CIA and collagen antibody induced arthritis (CAIA). Levels of anti-C5a antibodies and anti-collagen type II were measured by ELISA. C5a neutralization assay was done using a rat basophilic leukemia cell-line transfected with the human C5aR. Complement activity was determined using a hemolytic assay and joint morphology was assessed by histology. RESULTS: Vaccination of mice with MBP-C5a led to significant reduction of arthritis incidence and severity but not anti-collagen antibody synthesis. Histology of the MBP-C5a and control (MBP or PBS) vaccinated mice paws confirmed the vaccination effect. Sera from the vaccinated mice developed C5a-specific neutralizing antibodies, however C5 activation and formation of the membrane attack complex by C5b were not significantly altered. CONCLUSIONS: Exploitation of host immune response to generate sustained C5a neutralizing antibodies without significantly compromising C5/C5b activity is a useful strategy for developing an effective vaccine for antibody mediated and C5a dependent inflammatory diseases. Further developing of such a therapeutic vaccine would be more optimal and cost effective to attenuate inflammation without affecting host immunity

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

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

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