When is diabetes distress clinically meaningful?: establishing cut points for the Diabetes Distress Scale.

ObjectiveTo identify the pattern of relationships between the 17-item Diabetes Distress Scale (DDS17) and diabetes variables to establish scale cut points for high distress among patients with type 2 diabetes.Research design and methodsRecruited were 506 study 1 and 392 study 2 adults with type 2 diabetes from community medical groups. Multiple regression equations associated the DDS17, a 17-item scale that yields a mean-item score, with HbA(1c), diabetes self-efficacy, diet, and physical activity. Associations also were undertaken for the two-item DDS (DDS2) screener. Analyses included control variables, linear, and quadratic (curvilinear) DDS terms.ResultsSignificant quadratic effects occurred between the DDS17 and each diabetes variable, with increases in distress associated with poorer outcomes: study 1 HbA(1c) (P < 0.02), self-efficacy (P < 0.001), diet (P < 0.001), physical activity (P < 0.04); study 2 HbA(1c) (P < 0.03), self-efficacy (P < 0.004), diet (P < 0.04), physical activity (P = NS). Substantive curvilinear associations with all four variables in both studies began at unexpectedly low levels of DDS17: the slope increased linearly between scores 1 and 2, was more muted between 2 and 3, and reached a maximum between 3 and 4. This suggested three patient subgroups: little or no distress, <2.0; moderate distress, 2.0-2.9; high distress, ≥3.0. Parallel findings occurred for the DDS2.ConclusionsIn two samples of type 2 diabetic patients we found a consistent pattern of curvilinear relationships between the DDS and HbA(1c), diabetes self-efficacy, diet, and physical activity. The shape of these relationships suggests cut points for three patient groups: little or no, moderate, and high distress

Observations of the Ca II K line in Hel0830A dark points on August 3, 1985

Spectroheliograms taken in the light of He I 10830 A at the National Solar Observatory Vacuum Telescope on Kitt Peak were used to identify coronal holes and bright points (BPs). Target points were identified, coordinates calculated, and spectra recorded. For each spectrum, the difference in wavelength between the Ca II K minimum and the FeI reference line was calculated. It was noteworthy that the overall effect is a blueshift. It should be noted that if material of chromospheric density moves outward at this velocity, it could supply the mass flux of the solar wind if this chromospheric flow was concentrated in a few dozen sources, each of a diameter of a few arc seconds

Taking down ‘the Ivory Tower’: leveraging academia for better health outcomes in Uganda

http://deepblue.lib.umich.edu/bitstream/2027.42/112732/1/12914_2011_Article_147.pd

Disruption in Brain Phospholipid Content in a Humanized Tau Transgenic Model Following Repetitive Mild Traumatic Brain Injury

Repetitive mild traumatic brain injury (mTBI) is a risk factor for the development of neurodegenerative diseases such as chronic traumatic encephalopathy typified by immunoreactive tau aggregates in the depths of the sulci. However, the underlying neurobiological mechanisms involved have not been largely explored. Phospholipids are important molecules which form membrane lipid bilayers; they are ubiquitous to every cell in the brain, and carry out a host of different functions. Imbalance in phospholipid metabolism, signaling and transport has been documented in some neurological conditions. However, not much is currently known about their roles in repetitive mTBI and how this may confer risk for the development of age-related neurodegenerative diseases. To address this question, we designed a longitudinal study (24 h, 3, 6, 9, and 12 months post-injury) to comprehensively investigate mTBI dependent brain phospholipid profiles compared to sham counterparts. We use our established mouse model of repetitive mTBI that has been extensively characterized up to 1-year post-injury in humanized tau (hTau) mice, which expresses all six human tau isoforms, on a null murine background. Our data indicates a significant increase in sphingomyelin, phosphatidylethanolamine (PE), phosphatidylcholine (PC), and derivative lysoPE and lysoPC at acute and/or sub-acute time points post-injury within the cortex and hippocampus. There was also a parallel increase at early time points in monounsaturated, polyunsaturated and saturated fatty acids. Omega-6 (arachidonic acid) to omega-3 (docosahexaenoic acid) fatty acid ratio for PE and PC species was increased also at 24 h and 3 months post-injury in both hippocampus and cortex. The long-term consequences of these early changes in phospholipids on neuronal and non-neuronal cell function is unclear, and warrants further study. Understanding phospholipid metabolism, signaling and transport following TBI could be valuable; they may offer novel targets for therapeutic intervention not only in TBI but other neurodegenerative diseases

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Objective: Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival. Methods: Male C57BL/6J mice (aged 2–3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety-like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies. Results: At 24 months survival animals exposed to r-mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule-motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI. Interpretation: In this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI

Epidemiology of patients presenting to the emergency centre of Princess Marina Hospital in Gaborone, Botswana

Emergency medicine is a newly recognized specialty in Botswana and the country launched an emergency medicine residency in January 2011. Data regarding the practice of emergency medicine in Botswana are limited. This study reviewed 1 year of patient presentations to the emergency centre of Princess Marina Hospital, the country’s main referral hospital located in the capital city, Gaborone. Methods: Epidemiologic data of all patients presenting to the emergency centre between May 2010 and April 2011 were extracted into a database. The diagnoses of a random sample of patient presentations were coded using the categories outlined by the Clinical Classifications Software (CCS) for ICD-10. For ease of analysis, several CCS categories were grouped together for subsequent analysis. Results: 24,905 patient encounters were recorded during the study period. A large proportion of patients were aged between 25 and 50 years old. 20% of patients presented with a traumatic injury. The most common diagnoses across all ages included trauma, pregnancy complications, gastrointestinal disorders, and pneumonia. Conclusion: These results can inform the development of emergency medicine education and acute care systems in Botswana

Unbiased Proteomic Approach Identifies Unique and Coincidental Plasma Biomarkers in Repetitive mTBI and AD Pathogenesis

The relationship between repetitive mild traumatic brain injury (r-mTBI) and Alzheimer’s disease (AD) is well-recognized. However, the precise nature of how r-mTBI leads to or precipitates AD pathogenesis is currently not understood. Plasma biomarkers potentially provide non-invasive tools for detecting neurological changes in the brain, and can reveal overlaps between long-term consequences of r-mTBI and AD. In this study we address this by generating time-dependent molecular profiles of response to r-mTBI and AD pathogenesis in mouse models using unbiased proteomic analyses. To model AD, we used the well-validated hTau and PSAPP(APP/PS1) mouse models that develop age-related tau and amyloid pathological features, respectively, and our well-established model of r-mTBI in C57BL/6 mice. Plasma were collected at different ages (3, 9, and 15 months-old for hTau and PSAPP mice), encompassing pre-, peri- and post-“onset” of the cognitive and neuropathological phenotypes, or at different timepoints after r-mTBI (24 h, 3, 6, 9, and 12 months post-injury). Liquid chromatography/mass spectrometry (LC-MS) approaches coupled with Tandem Mass Tag labeling technology were applied to develop molecular profiles of protein species that were significantly differentially expressed as a consequence of mTBI or AD. Mixed model ANOVA after Benjamini–Hochberg correction, and a stringent cut-off identified 31 proteins significantly changing in r-mTBI groups over time and, when compared with changes over time in sham mice, 13 of these were unique to the injured mice. The canonical pathways predicted to be modulated by these changes were LXR/RXR activation, production of nitric oxide and reactive oxygen species and complement systems. We identified 18 proteins significantly changing in PSAPP mice and 19 proteins in hTau mice compared to their wild-type littermates with aging. Six proteins were found to be significantly regulated in all three models, i.e., r-mTBI, hTau, and PSAPP mice compared to their controls. The top canonical pathways coincidently changing in all three models were LXR/RXR activation, and production of nitric oxide and reactive oxygen species. This work suggests potential biomarkers for TBI and AD pathogenesis and for the overlap between these two, and warrant targeted investigation in human populations. Data are available via ProteomeXchange with identifier PXD010664

Promoting medical students’ reflection on competencies to advance a global health equities curriculum

Abstract Background The move to frame medical education in terms of competencies – the extent to which trainees “can do” a professional responsibility - is congruent with calls for accountability in medical education. However, the focus on competencies might be a poor fit with curricula intended to prepare students for responsibilities not emphasized in traditional medical education. This study examines an innovative approach to the use of potential competency expectations related to advancing global health equity to promote students’ reflections and to inform curriculum development. Methods In 2012, 32 medical students were admitted into a newly developed Global Health and Disparities (GHD) Path of Excellence. The GHD program takes the form of mentored co-curricular activities built around defined competencies related to professional development and leadership skills intended to ameliorate health disparities in medically underserved settings, both domestically and globally. Students reviewed the GHD competencies from two perspectives: a) their ability to perform the identified competencies that they perceived themselves as holding as they began the GHD program and b) the extent to which they perceived that their future career would require these responsibilities. For both sets of assessments the response scale ranged from “Strongly Disagree” to “Strongly Agree.” Wilcoxon’s paired T-tests compared individual students’ ordinal rating of their current level of ability to their perceived need for competence that they anticipated their careers would require. Statistical significance was set at p < .01. Results Students’ ratings ranged from “strongly disagree” to “strongly agree” that they could perform the defined GHD-related competencies. However, on most competencies, at least 50 % of students indicated that the stated competencies were beyond their present ability level. For each competency, the results of Wilcoxon paired T-tests indicate – at statistically significant levels - that students perceive more need in their careers for GHD-program defined competencies than they currently possess. Conclusion This study suggests congruence between student and program perceptions of the scope of practice required for GHD. Students report the need for enhanced skill levels in the careers they anticipate. This approach to formulating and reflecting on competencies will guide the program’s design of learning experiences aligned with students’ career goals.http://deepblue.lib.umich.edu/bitstream/2027.42/109541/1/12909_2013_Article_919.pd

Unbiased Proteomic Approach Identifies Pathobiological Profiles in the Brains of Preclinical Models of Repetitive Mild Traumatic Brain Injury, Tauopathy, and Amyloidosis

No concerted investigation has been conducted to explore overlapping and distinct pathobiological mechanisms between repetitive mild traumatic brain injury (r-mTBI) and tau/amyloid proteinopathies considering the long history of association between TBI and Alzheimer’s disease. We address this problem by using unbiased proteomic approaches to generate detailed time-dependent brain molecular profiles of response to repetitive mTBI in C57BL/6 mice and in mouse models of amyloidosis (with amyloid precursor protein KM670/671NL (Swedish) and Presenilin 1 M146L mutations [PSAPP]) and tauopathy (hTau). Brain tissues from animals were collected at different timepoints after injuries (24 hr–12 months post-injury) and at different ages for tau or amyloid transgenic models (3, 9, and 15 months old), encompassing the pre-, peri-, and post-“onset” of cognitive and pathological phenotypes. We identified 30 hippocampal and 47 cortical proteins that were significantly modulated over time in the r-mTBI compared with sham mice. These proteins identified TBI-dependent modulation of phosphatidylinositol-3-kinase/AKT signaling, protein kinase A signaling, and PPARα/RXRα activation in the hippocampus and protein kinase A signaling, gonadotropin-releasing hormone signaling, and B cell receptor signaling in the cortex. Previously published neuropathological studies of our mTBI model showed a lack of amyloid and tau pathology. In PSAPP mice, we identified 19 proteins significantly changing in the cortex and only 7 proteins in hTau mice versus wild-type littermates. When we explored the overlap between our r-mTBI model and the PSAPP/hTau models, a fairly small coincidental change was observed involving only eight significantly regulated proteins. This work suggests a very distinct TBI neurodegeneration and also that other factors are needed to drive pathologies such as amyloidosis and tauopathy postinjury