Center for Pediatric Obesity and Diabetes Prevention Research

poster abstractBackground To facilitate both research and treatment of obesity in youth who are at especially high risk for diabetes, we have created the Center for Pediatric Obesity and Diabetes Prevention Research. The mission of the center is to advance the health of vulnerable populations through obesity and diabetes prevention research focusing on mechanisms of progression from obesity to type 2 diabetes, defining best practices for obesity/diabetes prevention among youth, and cost-effective translation of the research to the community. Specific Aims 1. To promote the clinical investigation of pathophysiologic mechanisms, diagnosis, and primary prevention of type 2 diabetes among vulnerable youth 2. Foster collaboration and facilitate interdisciplinary research between investigators interested in childhood obesity and diabetes prevention 3. Participate in community-based diabetes prevention research Key Ongoing Collaborative Research Projects Youth Diabetes Prevention Clinic (YDPC) – Patient-Centered Outcomes Project This program is designed to evaluate and assess the needs of adolescents (ages 10 – 21) who have evidence of prediabetes. Our goal is to successfully intervene in the trajectory toward the development of diabetes, and to promote healthy weight-control and improved well-being through an individualized treatment plan. Not only has this allowed us to address a significant unmet clinical need, but also to advance pediatric obesity patient-centered outcomes research and comparative effectiveness research in adolescent obesity / diabetes prevention. Dietary Intervention for Glucose Intolerance in Teens (DIG-IT Study) The objective of this study is to determine the impact on glycemic control, in adolescents who have prediabetes, of an individually-tailored wellness coaching strategy used to modify lifestyle habits. Additionally, the study aims to identify lifestyle factors that drive glycemic control, independent of changes in weight. We are conducting this study in in the Youth Diabetes Prevention Clinic via a collaboration with Dr. Gletsu-Miller (Purdue University). ENCOURAGE Healthy Families Study This is a randomized trial evaluating the comparative effectiveness and costs of an adaptation of the Diabetes Prevention Program (DPP) directed at mothers and their children. The intervention is a group based lifestyle program which we developed and implemented in partnership with the YMCA. We are comparing the ENCOURAGE intervention targeted to 1) mothers who have had gestational diabetes or prediabetes, and 2) mothers who have had GDM or prediabetes along with their school-aged children

Analysis of atmospheric spectra for trace gases

The objective is the comprehensive analysis of high resolution atmospheric spectra recorded in the middle-infrared region to obtain simultaneous measurements of coupled parameters (gas concentrations of key trace constituents, total column amounts, pressure, and temperature) in the stratosphere and upper troposphere. Solar absorption spectra recorded at 0.002 and 0.02 cm exp -1 resolutions with the University of Denver group's balloon-borne, aircraft borne, and ground-based interferometers and 0.005 to 0.01 cm exp -1 resolution solar spectra from Kitt Peak are used in the analyses

Codesigned Shared Decision-Making Diabetes Management Plan Tool for Adolescents With Type 1 Diabetes Mellitus and Their Parents: Prototype Development and Pilot Test

Background: Adolescents with type 1 diabetes mellitus have difficulty achieving optimal glycemic control, partly due to competing priorities that interfere with diabetes self-care. Often, significant diabetes-related family conflict occurs, and adolescents’ thoughts and feelings about diabetes management may be disregarded. Patient-centered diabetes outcomes may be better when adolescents feel engaged in the decision-making process. Objective: The objective of our study was to codesign a clinic intervention using shared decision making for addressing diabetes self-care with an adolescent patient and parent advisory board. Methods: The patient and parent advisory board consisted of 6 adolescents (teens) between the ages 12 and 18 years with type 1 diabetes mellitus and their parents recruited through our institution’s Pediatric Diabetes Program. Teens and parents provided informed consent and participated in 1 or both of 2 patient and parent advisory board sessions, lasting 3 to 4 hours each. Session 1 topics were (1) patient-centered outcomes related to quality of life, parent-teen shared diabetes management, and shared family experiences; and (2) implementation and acceptability of a patient-centered diabetes care plan intervention where shared decision making was used. We analyzed audio recordings, notes, and other materials to identify and extract ideas relevant to the development of a patient-centered diabetes management plan. These data were visually coded into similar themes. We used the information to develop a prototype for a diabetes management plan tool that we pilot tested during session 2. Results: Session 1 identified 6 principal patient-centered quality-of-life measurement domains: stress, fear and worry, mealtime struggles, assumptions and judgments, feeling abnormal, and conflict. We determined 2 objectives to be principally important for a diabetes management plan intervention: (1) focusing the intervention on diabetes distress and conflict resolution strategies, and (2) working toward a verbalized common goal. In session 2, we created the diabetes management plan tool according to these findings and will use it in a clinical trial with the aim of assisting with patient-centered goal setting. Conclusions: Patients with type 1 diabetes mellitus can be effectively engaged and involved in patient-centered research design. Teens with type 1 diabetes mellitus prioritize reducing family conflict and fitting into their social milieu over health outcomes at this time in their lives. It is important to acknowledge this when designing interventions to improve health outcomes in teens with type 1 diabetes mellitus

Implications of the Optical Observations of Neutron Stars

We show that observations of pulsars with pulsed optical emission indicate that the peak flux scales according to the magnetic field strength at the light cylinder. The derived relationships indicate that the emission mechanism is common across all of the observed pulsars with periods ranging from 33ms to 385 ms and ages of 1000-300,000 years. It is noted that similar trends exist for $\gamma$ ray pulsars. Furthermore the model proposed by Pacini (1971) and developed by Pacini and Salvati (1983,1987) still has validity and gives an adequate explanation of the optical phenomena.Comment: 23 pages, 6 figures, accepted for publication in the Astrophysical Journa

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis.

RationaleThe monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.ObjectiveWe utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy.MethodsSerum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points.ResultsA total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status.ConclusionA comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care

Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy

AbstractLower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p=0.01) but were unchanged in controls (p=0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p<0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p=0.007 and p=0.001, respectively). Longitudinal increases in WMH (rs=0.04, p=0.86) or cerebral microbleeds (rs=−0.18, p=0.45) were not associated with the longitudinal decrease in BOLD amplitudes

Nuclear factor one transcription factors as epigenetic regulators in cancer

Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands imposed during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state. This stem cell-like phenotype primes tumour cells to react to external cues via the use of developmental pathways that facilitate changes in proliferation, migration and invasion. Because the dynamism of this stem cell-like state requires constant chromatin remodelling and rapid alterations at regulatory elements, it is of great therapeutic interest to identify the cell-intrinsic factors that confer these epigenetic changes that drive tumour progression. The nuclear factor one (NFI) family are transcription factors that play an important role in the development of many mammalian organ systems. While all four family members have been shown to act as either oncogenes or tumour suppressors across various cancer models, evidence has emerged implicating them as key epigenetic regulators during development and within tumours. Notably, NFIs have also been shown to regulate chromatin accessibility at distal regulatory elements that drive tumour cell dissemination and metastasis. Here we summarize the role of the NFIs in cancer, focusing largely on the potential mechanisms associated with chromatin remodelling and epigenetic modulation of gene expression

Characterization of Nursery Habitats used by Black Sea Bass and Summer Flounder in Chesapeake Bay and the Coastal Lagoons

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