2,569 research outputs found

    Characterization of A. baumannii Environmental Survival and Biofilm Formation and the Impact on Environmental Transmission.

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    Acinetobacter baumannii is a gram-negative, opportunistic pathogen primarily affecting the critically ill, causing 3% of all nosocomial-related deaths in the United States. A. baumannii’s successful environmental survival within the hospital environment is attributed to its ability to form biofilms, tolerate desiccation and be multidrug resistant (MDR). Understanding the relationship between these virulence factors will help minimize environmental-mediated transmissions of A. baumannii. To characterize fitness trade-offs imposed on A. baumannii by clinical and environmental settings, I compared rep-PCR banding patterns, antibiotic susceptibilities, biofilm formation and desiccation tolerance of 115 clinical and 54 environmental isolates collected from the University of Michigan Hospital. The MDR phenotype was deleterious for environmental-isolated strains (yet beneficial for patient-isolated strains) and biofilms were critical for environmental strain desiccation tolerance. This study improves our understanding of the association of the MDR phenotype with persistence, and demonstrates that the association is mediated by environmental conditions. Biofilms can disseminate contamination via detachment of sessile cells that are assumed characteristically planktonic. I investigated this assumption by comparing antibiotic susceptibilities of A. baumannii planktonic, biofilm, and detached sessile cells. Detached cells were phenotypically distinct with respect to antibiotic susceptibilities, suggesting that antibiotic therapies should target detached cells rather than planktonic cells for biofilm-related infections. A simplifying assumption in mathematical modeling is that the skin-surface exchange of contamination is symmetrical. My final study challenged this assumption by measuring the bi-directional transfer efficiencies of A. baumannii and evaluated the change in risk of pathogen transport between patients by comparing fate-and-transport mathematical models with contrasting symmetry assumptions. These studies demonstrated that the transfer efficiencies were asymmetrical and the assumption of symmetry minimized the true impact of healthcare worker-mediated transmission. This dissertation advances our understanding of the association between resistance, biofilms, and persistence. Results of my investigations will improve the accuracy of environmental-mediated infectious disease transmission system models and can be used to strengthen guidelines to control healthcare-associated infections. Further, the results provide new insights, that I hope will stimulate innovative approaches to reduce the risk of biofilm-related infections and curtail the environmental persistence and transmission of A. baumannii.PhDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116709/1/greene_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116709/2/greene_2.pd

    Judicial Review of the EEOC\u27s Duty To Conciliate

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    More than 50 years after the enactment of Title VII of the Civil Rights Act of 1964, federal courts remain unsettled on a variety of issues involving the Equal Employment Opportunity Commission\u27s ( EEOC ) pre-suit obligations. Title VII gives the EEOC the authority to enforce the statute\u27s prohibition on discrimination in the workplace. Before filing suit against an employer, the EEOC must satisfy several pre-suit requirements, including an attempt to eliminate the unlawful practice by informal methods of conference, conciliation, and persuasion. Courts disagree on the following: (1) whether the EEOC\u27s conciliation efforts are subject to judicial review; (2) what the standard of judicial review should be; (3) what the remedy should be if a court finds the EEOC failed to fulfill its pre-suit obligations; and (4) whether the EEOC may bring suit on behalf of unidentified individuals under § 706 of Title VII. In EEOC v. Mach Mining, LLC, the Court of Appeals for the Seventh Circuit was the first circuit court of appeals to find that conciliation efforts are a matter of agency discretion and are not subject to judicial review. Other courts have reviewed the conciliation process and have required that the EEOC demonstrate at least good faith efforts to conciliate. The U.S. Supreme Court granted Mach Mining\u27s petition for certiorari, and rendered its decision on April 29, 2015, as this article went to press. The Court did not specifically adopt the approach recommended by any of the lower courts. Although it disagreed with the Seventh Circuit\u27s conclusion that conciliation efforts are not reviewable, the Court\u27s decision and reasoning were more consistent with arguments made by the Seventh Circuit than by other circuit courts of appeal. The Supreme Court found that Title VII calls for a relatively barebones review of the EEOC\u27s efforts. To satisfy its pre-suit obligations, the Court stated, the EEOC must inform the employer of the specific allegation and identify which individuals or class of employees suffered from the alleged discrimination. The Commission must then engage in discussion with the employer to attempt to resolve the problem. The EEOC must present some evidence verifying its efforts to conciliate and a court may review an employer\u27s contention that conciliation did not occur. A court\u27s review of the conciliation efforts is limited to fact-finding on those issues, the Supreme Court stated. The Supreme Court\u27s decision largely echoes the Seventh Circuit\u27s concern that courts recognize the broad discretion that Title VII gives to the EEOC in resolving disputes, the importance of Title VII\u27s confidentiality provision, and Title VII\u27s overarching goal of eradicating discrimination in the workplace. The Court stated that the remedy for failure to conciliate is more conciliation and not dismissal on the merits

    SCOPE: Community Health Service at Pacific

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    The Student Community Outreach for Public Education (SCOPE) program is UoP’s student-run service organization that aims to serve the San Francisco Bay Area and beyond by putting on educational and community health events. The SCOPE Officers lead community health projects and encourage the student body to actively participate and volunteer in events that serve the community and various underserved neighborhoods in the city. Our 2019-2020 goal was to increase collaboration and improve class participation to help our peers foster the “Heart” component of UoP’s “Head, Heart, and Hand” philosophy

    The Potential of Teledentistry in Community Oral Health for the Pediatric Population

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    • Dental caries is the most prevalent chronic disease of childhood in the US. • Young children are a particularly vulnerable population because of their dependence, inability to communicate needs, and relative poverty. • Furthermore, this can be exacerbated by disparities such that an increased rates of caries are observed in children who are of low socioeconomic status and minority backgrounds. • However, community oral health screenings can play a vital role in childhood caries as a predominately preventable disease. • The current emphasis on social distance during the COVID-19 pandemic has brought attention to teledentistry, which may have a valuable role in the future of community oral health outreach

    Nurses Involvement in Nursing Home Culture Change: Overcoming Barriers, Advancing Opportunities

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    Summarizes discussions from a 2008 interdisciplinary panel convened to identify facilitators and barriers to nurses' involvement in culture change in nursing homes and actions to promote nurse competencies in resident-directed care. Makes recommendations

    Evidence-based practice implementation: The impact of public versus private sector organization type on organizational support, provider attitudes, and adoption of evidence-based practice

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    <p>Abstract</p> <p>Background</p> <p>The goal of this study is to extend research on evidence-based practice (EBP) implementation by examining the impact of organizational type (public versus private) and organizational support for EBP on provider attitudes toward EBP and EBP use. Both organization theory and theory of innovation uptake and individual adoption of EBP guide the approach and analyses in this study. We anticipated that private sector organizations would provide greater levels of organizational support for EBPs leading to more positive provider attitudes towards EBPs and EBP use. We also expected attitudes toward EBPs to mediate the association of organizational support and EBP use.</p> <p>Methods</p> <p>Participants were mental health service providers from 17 communities in 16 states in the United States (n = 170). Path analyses were conducted to compare three theoretical models of the impact of organization type on organizational support for EBP and of organizational support on provider attitudes toward EBP and EBP use.</p> <p>Results</p> <p>Consistent with our predictions, private agencies provided greater support for EBP implementation, and staff working for private agencies reported more positive attitudes toward adopting EBPs. Organizational support for EBP partially mediated the association of organization type on provider attitudes toward EBP. Organizational support was significantly positively associated with attitudes toward EBP and EBP use in practice.</p> <p>Conclusion</p> <p>This study offers further support for the importance of organizational context as an influence on organizational support for EBP and provider attitudes toward adopting EBP. The study demonstrates the role organizational support in provider use of EBP in practice. This study also suggests that organizational support for innovation is a malleable factor in supporting use of EBP. Greater attention should be paid to organizational influences that can facilitate the dissemination and implementation of EBPs in community settings.</p

    Heterogeneity in HIV and cellular transcription profiles in cell line models of latent and productive infection: implications for HIV latency.

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    BackgroundHIV-infected cell lines are widely used to study latent HIV infection, which is considered the main barrier to HIV cure. We hypothesized that these cell lines differ from each other and from cells from HIV-infected individuals in the mechanisms underlying latency.ResultsTo quantify the degree to which HIV expression is inhibited by blocks at different stages of HIV transcription, we employed a recently-described panel of RT-ddPCR assays to measure levels of 7 HIV transcripts ("read-through," initiated, 5' elongated, mid-transcribed/unspliced [Pol], distal-transcribed [Nef], polyadenylated, and multiply-sliced [Tat-Rev]) in bulk populations of latently-infected (U1, ACH-2, J-Lat) and productively-infected (8E5, activated J-Lat) cell lines. To assess single-cell variation and investigate cellular genes associated with HIV transcriptional blocks, we developed a novel multiplex qPCR panel and quantified single cell levels of 7 HIV targets and 89 cellular transcripts in latently- and productively-infected cell lines. The bulk cell HIV transcription profile differed dramatically between cell lines and cells from ART-suppressed individuals. Compared to cells from ART-suppressed individuals, latent cell lines showed lower levels of HIV transcriptional initiation and higher levels of polyadenylation and splicing. ACH-2 and J-Lat cells showed different forms of transcriptional interference, while U1 cells showed a block to elongation. Single-cell studies revealed marked variation between/within cell lines in expression of HIV transcripts, T cell phenotypic markers, antiviral factors, and genes implicated in latency. Expression of multiply-spliced HIV Tat-Rev was associated with expression of cellular genes involved in activation, tissue retention, T cell transcription, and apoptosis/survival.ConclusionsHIV-infected cell lines differ from each other and from cells from ART-treated individuals in the mechanisms governing latent HIV infection. These differences in viral and cellular gene expression must be considered when gauging the suitability of a given cell line for future research on HIV. At the same time, some features were shared across cell lines, such as low expression of antiviral defense genes and a relationship between productive infection and genes involved in survival. These features may contribute to HIV latency or persistence in vivo, and deserve further study using novel single cell assays such as those described in this manuscript

    Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1

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    Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions
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