168 research outputs found

    Theories of State Recovery under CERCLA for Injuries to the Environment

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    Assessment of musculoskeletal examination skills of 4th year medical students using a novel OSCE

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    Objective: Despite the high prevalence of musculoskeletal complaints presenting to physicians in the United States, there are very few opportunities for University of Michigan clinical medical students to receive formative or summative assessment of their ability to evaluate patients with these complaints. The purpose of this study was to assess 4th year students’ ability to examine and diagnose several common musculoskeletal disorders using a novel objective structured clinical examination (OSCE). Methods: A multidisciplinary team of musculoskeletal specialists developed the content and structure of three OSCE stations focusing on examination of the shoulder, back and knee. For each station, volunteer M4 students were provided a clinical vignette with three possible diagnoses to consider, and were instructed to anticipate physical examination maneuvers or findings that would discriminate between the three diagnoses. Then they would examine a professional patient simulating findings associated with one of the diagnoses and choose their favored diagnosis. Their encounter was directly observed by a faculty member who scored their performance on selected physical examination maneuvers based on a checklist (0 = not done, 1 = partially done, 2 = fully done). Each encounter was recorded to allow for later review by another faculty. Immediate feedback was provided to students at the end of the OSCE, making this a formative as well as summative assessment experience. Faculty received verbal and written instruction on how to score students. IRB exemption was obtained for this study. Results: 44 M4 students participated in the OSCE during the spring of 2012. General performance of M4 students in examining regional musculoskeletal complaints will be reported. Performance of individuals will be correlated with: anticipation of discriminatory features prior to examining the patients; self-assessment on ability to perform the relevant exam and anticipated need to do so in their future career; previous musculoskeletal elective exposure; future career choice; and performance on the M4 Comprehensive Clinical Assessment “Back pain” and “Abdominal pain” stations. Conclusions: Initial validity evidence for a multistation musculoskeletal OSCE will be presented, as will the performance of a sampling of the 2012 graduating UM medical student class. This data will be used as part of ongoing evaluation of the longitudinal musculoskeletal curriculum at the University of Michigan medical school.http://deepblue.lib.umich.edu/bitstream/2027.42/91291/1/MedEdDay2012-poster-monradetal.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91291/3/MEDC22poster.pd

    Economic and other barriers to adopting recommendations to prevent childhood obesity: results of a focus group study with parents

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    Abstract Background Parents are integral to the implementation of obesity prevention and management recommendations for children. Exploration of barriers to and facilitators of parental decisions to adopt obesity prevention recommendations will inform future efforts to reduce childhood obesity. Methods We conducted 4 focus groups (2 English, 2 Spanish) among a total of 19 parents of overweight (BMI ≥ 85th percentile) children aged 5-17 years. The main discussion focused on 7 common obesity prevention recommendations: reducing television (TV) watching, removing TV from child's bedroom, increasing physically active games, participating in community or school-based athletics, walking to school, walking more in general, and eating less fast food. Parents were asked to discuss what factors would make each recommendation more difficult (barriers) or easier (facilitators) to follow. Participants were also asked about the relative importance of economic (time and dollar costs/savings) barriers and facilitators if these were not brought into the discussion unprompted. Results Parents identified many barriers but few facilitators to adopting obesity prevention recommendations for their children. Members of all groups identified economic barriers (time and dollar costs) among a variety of pertinent barriers, although the discussion of dollar costs often required prompting. Parents cited other barriers including child preference, difficulty with changing habits, lack of information, lack of transportation, difficulty with monitoring child behavior, need for assistance from family members, parity with other family members, and neighborhood walking safety. Facilitators identified included access to physical activity programs, availability of alternatives to fast food and TV which are acceptable to the child, enlisting outside support, dietary information, involving the child, setting limits, making behavior changes gradually, and parental change in shopping behaviors and own eating behaviors. Conclusions Parents identify numerous barriers to adopting obesity prevention recommendations, most notably child and family preferences and resistance to change, but also economic barriers. Intervention programs should consider the context of family priorities and how to overcome barriers and make use of relevant facilitators during program development.http://deepblue.lib.umich.edu/bitstream/2027.42/78270/1/1471-2431-9-81.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78270/2/1471-2431-9-81.pdfPeer Reviewe

    A Polymorphism of Bactericidal/Permeability-Increasing Protein Affects Its Neutralization Efficiency towards Lipopolysaccharide

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    Gram-negative sepsis driven by lipopolysaccharide (LPS) has detrimental outcomes, especially in neonates. The neutrophil-derived bactericidal/permeability-increasing protein (BPI) potently neutralizes LPS. Interestingly, polymorphism of the BPI gene at position 645 (rs4358188) corresponds to a favorable survival rate of these patients in the presence of at least one allele 645 A as opposed to 645 G. When we exploited the existing X-ray crystal structure, the corresponding amino acid at position 216 was revealed as surface exposed and proximal to the lipid-binding pocket in the N-terminal domain of BPI. Our further analysis predicted a shift in surface electrostatics by a positively charged lysine (BPI216K) exchanging a negatively charged glutamic acid (BPI216E). To investigate differences in interaction with LPS, we expressed both BPI variants recombinantly. The amino acid exchange neither affected affinity towards LPS nor altered bactericidal activity. However, when stimulating human peripheral blood mononuclear cells, BPI216K exhibited a superior LPS-neutralizing capacity (IC50 12.0 ± 2.5 pM) as compared to BPI216E (IC50 152.9 ± 113.4 pM, p = 0.0081) in respect to IL-6 secretion. In conclusion, we provide a functional correlate to a favorable outcome of sepsis in the presence of BPI216K

    The Grizzly, April 29, 2010

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    Active Minds Hosts Art Fair to Benefit Mental Health • Students Say Farewell Through Presidential Celebration • UCDC Hosts Spring Concert in Lenfest Theater • Dr. Spencer Foreman: Counting Down the Reasons • Workout and Have Fun at Ursinus Zumba-Thon! • Music and Diplomacy Converge to Help Alleviate HIV and AIDS • Professor Mudd\u27s CIE III Class Explores Happiness and the UC Student Body • Class of 2010 Spotlight: Seniors Reflect on UC Memories • Ursinus College Mourns the Loss of a Legend • Senior Spotlight: Mark Worrilow, Footballhttps://digitalcommons.ursinus.edu/grizzlynews/1813/thumbnail.jp

    Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition

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    Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) neutralizes endotoxic activity of lipopolysaccharides, and thus prohibits hyperactivation. So far, no immunological function of BPI has been described in Gram-positive infections. Here, we show a significant elevation of BPI in Gram-positive meningitis and, surprisingly, a positive correlation between BPI and pro-inflammatory markers like TNF alpha. To clarify the underlying mechanisms, we identify BPI ligands of Gram-positive origin, specifically bacterial lipopeptides and lipoteichoic acids, and determine essential structural motifs for this interaction. Importantly, the interaction of BPI with these newly defined ligands significantly enhances the immune response in peripheral blood mononuclear cells (PBMCs) mediated by Gram-positive bacteria, and thereby ensures their sensitive perception. In conclusion, we define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections

    Global Regulation of Nucleotide Biosynthetic Genes by c-Myc

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    The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP-PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated.Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis.Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis

    Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

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    Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

    Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response

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    Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression. Conventional DCs also respond to BPI, while M-CSF-cultivated or peritoneal lavage macrophages do not. Subsequent to BPI stimulation of BMDCs, CD4+ T cells predominantly secrete IL-22 and, when naive, preferentially differentiate into T helper 22 (Th22) cells. Congruent with the tissue-protective properties of IL-22 and along with impaired IL-22 induction, disease severity is significantly increased during dextran sodium sulfate-induced colitis in BPI-deficient mice. Importantly, physiological diversification of intestinal microbiota fosters BPI-dependent IL-22 induction in CD4+ T cells derived from mesenteric lymph nodes. In conclusion, BPI is a potent activator of DCs and consecutive Th22 cell differentiation with substantial relevance in intestinal homeostasis
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