Identifying Dimensions of Montana Tribal Community Capacity in Relation to the Funding Application Process

Foundations and government agencies have historically played a critical role in supporting community-based health promotion programs (Easterling, Gallagher & Lodwich, 2003). Despite availability of federal and state funding for health promotion efforts within American Indian reservation communities in Montana, tribal communities in the state are less likely than non-tribal communities to successfully apply for funding for health and social services (Lonsdale, T., personal communication, April 1, 2011). Increased access to health promotion funding may help address significant health issues existing within American Indian communities such as childhood obesity, diabetes type 2, and cardiovascular disease (Ogden, Flegal, Carroll & Johnson, 2002; Brown, Noonan, Friede & Giroux, 2008; Cooper, Andersen, Wederkopp, Page & Frosberg, 2005; Robert Wood Johnson Foundation, 2009). Understanding the relationship between the capacity of American Indian (AI) communities to successfully apply for and receive funding and the capacity of funding agencies to effectively receive applications from and partner with tribal communities may serve to increase resources for health promotion efforts within tribal communities in Montana. This exploratory qualitative study completed 17 semi-structured interviews across three AI reservations in the state of Montana. Dimensions of community capacity within the context of the funding application process and funding partnership with funding agencies were identified, including resources, leadership, community need, networks, and relationship with the funding agency. Dimensions of tribal community capacity were then used to suggest potential capacity building strategies for improved funding partnership between tribal communities in Montana and funding agencies. Capacity building strategies such as strategic planning for organizational change by leadership and community-based organizations, increased opportunities for community member participation and inclusion in expressing needs and concerns, and a monthly meeting for community grant seekers to raise awareness about and prioritize funding opportunities were suggested for tribal communities, while strategies such as the provision of consistent technical assistance, a focus on relationship-building, and making available funding opportunities for the specific purpose of tribal community capacity in the funding application process are examples of changes for on the funding agency side. These strategies could be further developed in an attempt to build the capacity of tribal communities to secure more funding for local health promotion efforts

Myeloproliferative and lymphoproliferative malignancies occurring in the same patient:a nationwide discovery cohort

Myeloid and lymphoid malignancies are postulated to have distinct pathogenetic mechanisms. The recent observation that patients with a myeloproliferative neoplasm have an increased risk of developing lymphoproliferative malignancy has challenged this assumption. We collected a nationwide cohort of patients with both malignancies. Patients diagnosed in 1990-2015 were identified through the national Danish Pathology Registry. We identified 599 patients with myeloproliferative neoplasm and a concomitant or subsequent diagnosis of lymphoma. Histopathological review of the diagnostic samples from each patient led to a final cohort of 97 individuals with confirmed dual diagnoses of myeloproliferative neoplasm and lymphoma. The age range at diagnosis was 19-94 years (median: 71 years). To avoid the inclusion of cases of therapy-induced myeloproliferative neoplasm occurring in patients previously treated for lymphoma, only patients with myeloproliferative neoplasm diagnosed unequivocally before the development of lymphoma were included. The average time interval between the diagnoses of the two malignancies was 1.5 years. In the majority of patients (90%) both diagnoses were established within 5 years from each other. Among the lymphoma entities, the frequency of peripheral T-cell lymphomas was markedly increased. Interestingly, all but one of the T-cell lymphomas were of angioimmunoblastic type. These findings suggest that myeloproliferative neoplasm and lymphoproliferative malignancy developing in the same patient may have common pathogenetic events, possibly already at progenitor level. We believe that the molecular characterization of the newly developed biorepository will help to highlight the mechanisms driving the genesis and clonal evolution of these hematopoietic malignancies

Gene Expression in Skeletal Muscle Biopsies from People with Type 2 Diabetes and Relatives: Differential Regulation of Insulin Signaling Pathways

BACKGROUND:Gene expression alterations have previously been associated with type 2 diabetes, however whether these changes are primary causes or secondary effects of type 2 diabetes is not known. As healthy first degree relatives of people with type 2 diabetes have an increased risk of developing type 2 diabetes, they provide a good model in the search for primary causes of the disease. METHODS/PRINCIPAL FINDINGS:We determined gene expression profiles in skeletal muscle biopsies from Caucasian males with type 2 diabetes, healthy first degree relatives, and healthy controls. Gene expression was measured using Affymetrix Human Genome U133 Plus 2.0 Arrays covering the entire human genome. These arrays have not previously been used for this type of study. We show for the first time that genes involved in insulin signaling are significantly upregulated in first degree relatives and significantly downregulated in people with type 2 diabetes. On the individual gene level, 11 genes showed altered expression levels in first degree relatives compared to controls, among others KIF1B and GDF8 (myostatin). LDHB was found to have a decreased expression in both groups compared to controls. CONCLUSIONS/SIGNIFICANCE:We hypothesize that increased expression of insulin signaling molecules in first degree relatives of people with type 2 diabetes, work in concert with increased levels of insulin as a compensatory mechanism, counter-acting otherwise reduced insulin signaling activity, protecting these individuals from severe insulin resistance. This compensation is lost in people with type 2 diabetes where expression of insulin signaling molecules is reduced

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD