Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women

<p>Abstract</p> <p>Background</p> <p>The prevalence of type 2 diabetes is higher among African Americans (AA) vs European Americans (EA), independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women.</p> <p>Methods</p> <p>Subjects were 115 African American (AA) and 137 European American (EA) healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (S_I) with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry.</p> <p>Results</p> <p>Vitamin D intake was positively associated with S_I(standardized β = 0.18, <it>P </it>= 0.05) and inversely associated with HOMA-IR (standardized β = -0.26, <it>P </it>= 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, <it>P </it>= 0.74 and standardized β = 0.02, <it>P </it>= 0.85 for S_Iand HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with S_Iand HOMA-IR among AA but not EA.</p> <p>Conclusions</p> <p>This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.</p

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Evaluation of adenovirus capsid labeling versus transgene expression

Adenoviral vectors have been utilized for a variety of gene therapy applications. Our group has incorporated bioluminescent, fluorographic reporters, and/or suicide genes within the adenovirus genome for analytical and/or therapeutic purposes. These molecules have also been incorporated as capsid components. Recognizing that incorporations at either locale yield potential advantages and disadvantages, our report evaluates the benefits of transgene incorporation versus capsid incorporation. To this end, we have genetically incorporated firefly luciferase within the early region 3 or at minor capsid protein IX and compared vector functionality by means of reporter readout

Best Practices for Biostatistical Consultation and Collaboration in Academic Health Centers

Given the increasing level and scope of biostatistics expertise needed at academic health centers today, we developed best practices guidelines for biostatistics units to be more effective in providing biostatistical support to their institutions, and in fostering an environment in which unit members can thrive professionally. Our recommendations focus on the key areas of: 1) funding sources and mechanisms; 2) providing and prioritizing access to biostatistical resources; and 3) interacting with investigators. We recommend that the leadership of biostatistics units negotiate for sufficient long-term infrastructure support to ensure stability and continuity of funding for personnel, align project budgets closely with actual level of biostatistical effort, devise and consistently apply strategies for prioritizing and tracking effort on studies, and clearly stipulate with investigators prior to project initiation policies regarding funding, lead time, and authorship

Leadership Reconsidered: Engaging Higher Education in Social Change

Colleges and universities can provide effective environments for the development of future leaders. This book addresses the application of transformative leadership to higher education, identifies resources to use in the process, and..

Early Identification and Prevention of the Spread of Ebola - United States

In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC\u27s technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new strategies: 1) active monitoring of travelers arriving from countries affected by Ebola and other persons at risk for Ebola and 2) a tiered system of hospital facility preparedness that enabled prioritization of training. CDC rapidly deployed a diagnostic assay for Ebola virus (EBOV) to public health laboratories. Guidance was developed to assist in evaluation of patients possibly infected with EBOV, for appropriate infection control, to support emergency responders, and for handling of infectious waste. CDC rapid response teams were formed to provide assistance within 24 hours to a health care facility managing a patient with Ebola. As a result of the collaborations to rapidly identify, isolate, and manage Ebola patients and the extensive preparations to prevent spread of EBOV, the United States is now better prepared to address the next global infectious disease threat.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html)

Plasma TGF-β1 in pediatric cystic fibrosis: Potential biomarker of lung disease and response to therapy

Transforming growth factor beta-1 (TGF-β1) is an important genetic modifier of lung disease severity in cystic fibrosis (CF), yet the mechanism behind this disease association remains unknown. Initial steps in the investigation of the relationship between TGF-β1 and CF lung disease include determining the most appropriate available biospecimen for TGF-β1 protein measurement

Targeting the effector domain of the myristoylated alanine rich C-kinase substrate enhances lung cancer radiation sensitivity

Lung cancer is the leading cause of cancer related deaths. Common molecular drivers of lung cancer are mutations in receptor tyrosine kinases (RTKs) leading to activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pro-growth, pro-survival signaling pathways. Myristoylated alanine rich C-kinase substrate (MARCKS) is a protein that has the ability to mitigate this signaling cascade by sequestering the target of PI3K, phosphatidylinositol (4,5)-bisphosphate (PIP2). As such, MARCKS has been implicated as a tumor suppressor, though there is some evidence that MARCKS may be tumor promoting in certain cancer types. Since the MARCKS function depends on its phosphorylation status, which impacts its subcellular location, MARCKS role in cancer may depend highly on the signaling context. Currently, the importance of MARCKS in lung cancer biology is limited. Thus, we investigated MARCKS in both clinical specimens and cell culture models. Immunohistochemistry scoring of MARCKS protein expression in a diverse lung tumor tissue array revealed that the majority of squamous cell carcinomas stained positive for MARCKS while other histologies, such as adenocarcinomas, had lower levels. To study the importance of MARCKS in lung cancer biology, we used inducible overexpression of wild-type (WT) and non-phosphorylatable (NP)-MARCKS in A549 lung cancer cells that had a low level of endogenous MARCKS. We found that NP-MARCKS expression, but not WT-MARCKS, enhanced the radiosensitivity of A549 cells in part by inhibiting DNA repair as evidenced by prolonged radiation-induced DNA double strand breaks. We confirmed the importance of MARCKS phosphorylation status by treating several lung cancer cell lines with a peptide mimetic of the phosphorylation domain, the effector domain (ED), which effectively attenuated cell growth as measured by cell index. Thus, the MARCKS ED appears to be an important target for lung cancer therapeutic development

Structure of the Mg-Chelatase Cofactor GUN4 Reveals a Novel Hand-Shaped Fold for Porphyrin Binding

In plants, the accumulation of the chlorophyll precursor Mg-protoporphyrin IX (Mg-Proto) in the plastid regulates the expression of a number of nuclear genes with functions related to photosynthesis. Analysis of the plastid-to-nucleus signaling activity of Mg-Proto in Arabidopsis thaliana led to the discovery of GUN4, a novel porphyrin-binding protein that also dramatically enhances the activity of Mg-chelatase, the enzyme that synthesizes Mg-Proto. GUN4 may also play a role in both photoprotection and the cellular shuttling of tetrapyrroles. Here we report a 1.78-Å resolution crystal structure of Synechocystis GUN4, in which the porphyrin-binding domain adopts a unique three dimensional fold with a “cupped hand” shape. Biophysical and biochemical analyses revealed the specific site of interaction between GUN4 and Mg-Proto and the energetic determinants for the GUN4 • Mg-Proto interaction. Our data support a novel protective function for GUN4 in tetrapyrrole trafficking. The combined structural and energetic analyses presented herein form the physical-chemical basis for understanding GUN4 biological activity, including its role in the stimulation of Mg-chelatase activity, as well as in Mg-Proto retrograde signaling

The potential of trading activity income to fund third sector organisations operating in deprived areas

In the United Kingdom, as in other countries, Third Sector Organisations (TSOs) have been drawn towards income sources associated with trading activities (Teasdale, 2010), but many remain reliant on grant funding to support such activities (Chell, 2007). Using a multivariate analysis approach and data from the National Survey of Charities and Social Enterprises (NSCSE), it is found that trading activities are used relatively commonly in deprived areas. These organisations are also more likely to attempt to access public sector funds. This suggests policy-makers need to consider the impact of funding cuts on TSOs in the most deprived areas as TSOs are unlikely achieve their objectives without continuing support