Organizational readiness for wellness promotion - a survey of 100 African American church leaders in South Los Angeles.

BackgroundChurches are an important asset and a trusted resource in the African American community. We needed a better understanding of their readiness to engage in health promotion before launching a large-scale health promotion effort in partnership with South Los Angeles churches.MethodsIn 2017, we conducted surveys with leaders of 100 churches. Surveys were conducted face-to-face (32%) or by telephone (68%) with senior pastors (one per church) and lasted on average 48 min. We compared small (less than 50 active members), medium (50-99 active members) and large churches (at least 100 active members), and assessed which church characteristics were associated with the implementation of wellness activities.ResultsMedium and large churches conducted significantly more wellness activities than small churches and were more likely to have wellness champions and health policies. Regardless of church size, insufficient budget was the most commonly cited barrier to implement wellness activities (85%). A substantial proportion of churches was not sure how to implement wellness activities (61%) and lacked volunteers (58%). Forty-five percent of the variation in the number of wellness activities in the last 12 months was explained by church characteristics, such as size of congregation, number of paid staff, leadership engagement, having a wellness ministry and barriers.ConclusionsMany churches in South Los Angeles are actively engaged in health promotion activities, despite a general lack of resources. We recommend a comprehensive assessment of church characteristics in intervention studies to enable the use of strategies (e.g., stratification by size) that reduce imbalances that could mask or magnify study outcomes. Our data provide empirical support for the inner settings construct of the Consolidated Framework for Implementation Research in the context of health promotion in African American churches

Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

BackgroundAlthough the contrast-enhancing (CE) lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden.MethodsFifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy.ResultsThe Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data.ConclusionsThe similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence

IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. Herpes viruses induce IL-10 to modulate the virus-host balance towards their own benefit, resulting in prolonged virus persistence. To define the cellular and molecular players involved in IL-10 modulation of herpes virus-specific immunity, we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10 specifically curtails the MCMV-specific CD4 T cell response by suppressing the bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T cells and we defined the pro-inflammatory cytokines IL-12, IFN-γ and TNF-α as well as NK cell activating receptors NKG2D and NCR-1 to regulate this bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV-specific CD4 T cells in Il10-/-mice led to faster control of lytic viral replication, bu

A genome-wide association study of Hodgkin Lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21, and 10p14 (GATA3)

To identify predisposition loci for classical Hodgkin Lymphoma (cHL) we conducted a genome-wide association study of 589 cHL cases and 5,199 controls with validation in 4 independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL; odds ratio [OR]=1.22, Pcombined=1.91×10−8), 8q24.21 (rs2019960, PVT1; OR=1.33, Pcombined=1.26×10−13) and 10p14 (rs501764, GATA3; OR=1.25, Pcombined=7.05×10−8). Furthermore, we confirmed the role of the MHC in disease etiology by revealing a strong HLA association (rs6903608; OR=1.70, Pcombined=2.84×10−50). These data provide new insight into the pathogenesis of cHL

Enabling meta-analysis in systematic reviews on carpal tunnel syndrome

Possible solutions to the problems of clinical heterogeneity of outcome measures and inadequate reporting of results for randomized controlled trials (RCTs) on carpal tunnel syndrome (CTS) are presented. Meta-analysis was impeded by these problems in 2 systematic reviews concerning conservative and surgical treatment options for CTS. A solution to the problem of inadequate data presentation is to add explicit information on minimal requirements with regard to data presentation to guidelines for the reporting of studies. To resolve the problem of clinical heterogeneity of the outcomes there should be consensus on the (validated) outcomes that should be used in RCTs. For CTS there is little evidence available on the reliability, validity, and responsiveness to change of the commonly used outcomes in RCTs. Resolving both problems will increase the comparability of RCTs, enabling the calculation of a pooled estimate of effect in a meta-analysi

Not All Play Equipment Is Created Equal: Associations Between Equipment at Home and Children’s Physical Activity

Background: Play equipment at home could be targeted in interventions to increase children’s physical activity (PA), but evidence is mixed, potentially because current methods do not reflect children’s lived experience. This study investigated associations between combinations of equipment and PA. Methods: Data were from the Mothers and their Children’s Health study and the Australian Longitudinal Study on Women’s Health. Mothers (n = 2409) indicated the types of fixed active (eg, trampolines), portable active (eg, bicycles), and electronic (eg, computers) equipment at home, and the number of days children (n = 4092, aged 5–12 y, 51% boys) met PA guidelines. Latent class analysis was used to identify combinations of equipment, and linear regressions were used to investigate associations with PA. Results: Compared with children with high active (fixed and portable) and medium electronic equipment, children with portable active and medium (B = −0.53; 95% confidence interval, −0.72 to −0.34) or high (B = −0.58; 95% confidence interval, −0.83 to −0.33) electronic equipment met the guidelines on fewer days. Children with similar active equipment (but more electronic equipment) met the PA guidelines on fewer days (mean difference = −0.51, SE = 0.14, P = .002). Conclusion: Having the right combination of play equipment at home may be important for children’s PA

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk