115 research outputs found

    Using Experiential and Collaborative Methods with Undergraduates and Older Persons as part of an Introduction to Gerontology Course

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    This study examines an Introduction to Gerontology course for undergraduate students that integrates experiential and collaborative learning experiences as part of a general course requirement. Experiential learning encourages students to go outside of the classroom and learn about aging from an older person in a field setting. The collaborative group approach is designed to have peers work together in the course. This study used qualitative methods to examine undergraduates’ learning experiences as a result of participation in a multiple-interview and groupwork-based project through their enrollment in the Introduction to Gerontology course. Content analysis was used to analyze multiple sources of data produced by the 43 students enrolled. Data were retrieved from students’ self-reflections in open-ended questionnaires and blinded course evaluations along with the authors’ own observational work. Findings indicate that students benefited from the experiential component which served to dispel stereotypes and preconceived ideas about older persons, though that did not necessarily translate into generating students’ interest in making gerontology a career path. Collaborative work, although seen generally as positive, had some mixed results based on students’ roles in the group and dynamics of a few groups. Issues of some student roles in the group unexpectedly not meeting with the older person are also discussed along with the impact of the project upon the community-partnered organization

    High level expression of a glutamate-gated chloride channel gene in reproductive tissues of Brugia malayi may explain the sterilizing effect of ivermectin on filarial worms

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    AbstractGlutamate-gated chloride channels (GluCl) are targets for avermectin/milbemycin (A/M) anthelmintics such as ivermectin that cause paralysis of somatic and pharyngeal muscles in gastrointestinal nematodes. Ivermectin is useful for onchocerciasis control programs because of its activity against microfilariae that often cause ocular disease and severe dermatitis. However, mechanisms responsible for reduced microfilaria production by adult worms following ivermectin treatment are poorly understood. We synthesized subunit-specific RNA probes for the Brugia malayi GluCl gene avr-14 (BmAVR-14) to localize expression of this gene in adult filarial worms. Both subunits of BmAVR-14 exhibited very similar expression patterns. In female worms, strong expression signals were detected in the ovary, developing embryos and lateral hypodermal chords, with moderate expression in the uterus wall adjacent to stretched microfilariae. These genes were also highly expressed in adult male worms (in spermatogonia, in the wall of the vas deferens, and in the lateral chords, but not in mature spermatozoa). In addition, avr-14 was highly expressed in somatic muscles adjacent to the terminal end of the vas deferens which contains mature sperm. These results show that avr-14 is highly expressed in B. malayi developing embryos and reproductive tissues, and they provide evidence for the involvement of GluCl in gamete production and embryogenesis in filarial worms. This may explain the observed suppression of microfilaria (Mf) production by female worms following treatment with avermectin/milbemycin anthelmintics

    Antibody responses to Brugia malayi antigens induced by DNA vaccination

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    BACKGROUND: DNA vaccination is a convenient means of immunizing animals with recombinant parasite antigens. DNA delivery methods are believed to affect the qualitative nature of immune responses to DNA vaccines in ways that may affect their protective activity. However, relatively few studies have directly compared immune responses to plasmids encoding the same antigens after injection by different routes. Therefore, the purpose of this study was to explore the influence of the route of administration on antibody responses to plasmids encoding antigens from the filarial nematode parasite Brugia malayi. METHODS: Four B. malayi genes and partial genes encoding paramyosin (BM5), heat shock protein (BMHSP-70), intermediate filament (BMIF) and a serodiagnostic antigen (BM14) were inserted in eukaryotic expression vectors (pJW4303 and pCRâ„¢3.1). BALB/c mice were immunized with individual recombinant plasmids or with a cocktail of all four plasmids by intramuscular injection (IM) or by gene gun-intradermal inoculation (GG). Antibody responses to recombinant antigens were measured by ELISA. Mean IgG1 to IgG2a antibody ratios were used as an indicator of Th1 or Th2 bias in immune responses induced with particular antigens by IM or GG immunization. The statistical significance of group differences in antibody responses was assessed by the non-parametric Kruskal-Wallis test. RESULTS: Mice produced antibody responses to all four filarial antigens after DNA vaccination by either the IM or GG route. Antibody responses to BM5 paramyosin were strongly biased toward IgG1 with lower levels of IgG2a after GG vaccination, while IM vaccination produced dominant IgG2a antibody responses. Antibody responses were biased toward IgG1 after both IM and GG immunization with BMIF, but antibodies were biased toward IgG2a after IM and GG vaccination with BMHSP-70 and BM14. Animals injected with a mixture of four recombinant plasmid DNAs produced antibodies to all four antigens. CONCLUSIONS: Our results show that monovalent and polyvalent DNA vaccination successfully induced antibody responses to a variety of filarial antigens. However, antibody responses to different antigens varied in magnitude and with respect to isotype bias. The isotype bias of antibody responses following DNA vaccination can be affected by route of administration and by intrinsic characteristics of individual antigens

    Characterization of glycan determinants that mediate recognition of the major Wuchereria bancrofti circulating antigen by diagnostic antibodies

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    The Global Program to Eliminate Lymphatic Filariasis (GPELF) relies heavily on a rapid diagnostic test (RDT) to a Wuchereria bancrofti circulating filarial antigen (Wb-CFA) to identify endemic areas and for determining when mass drug administration can stop. The antigen contains a carbohydrate epitope that is recognized by monoclonal antibody AD12. Og4C3, a monoclonal antibody that is used in a commercial ELISA for Wb-CFA recognizes the same moiety. Despite its diagnostic importance, little is known about the structure and function of this AD12 epitope . It is also present on other W. bancrofti glycoproteins and on glycoproteins of other filarial worms, but such antigens are not detected in the sera of individuals with most other filarial infections. We report here functional and biochemical analyses that shed light on the interaction between filarial glycoproteins and AD12 and/or Og4C3. Binding of these monoclonal antibodies to a mammalian glycan array suggests the reactive moiety has structural similarity to terminal β-d-glucuronic acid in a 1-3 linkage to other hexoses. However, sera collected from individuals with patent W. bancrofti infection had very low or undetectable serum antibodies to the GlcA-containing array glycans. Unlike other filarial glycoproteins, the Wb-CFA is relatively resistant to protease digestion by pronase and trypsin and completely resistant to the mucinase O-sialoglycoprotein endopeptidase (OSGE). The protease resistance of the Wb-CFA may contribute to its consistent detection in Wb-infected sera

    Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3

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    Background: Filarial nematode parasites cause serious diseases such as elephantiasis and river blindness in humans, and heartworm infections in dogs. Third stage filarial larvae (L3) are a critical stage in the life cycle of filarial parasites, because this is the stage that is transmitted by arthropod vectors to initiate infections in mammals. Improved understanding of molecular mechanisms associated with this transition may provide important leads for development of new therapies and vaccines to prevent filarial infections. This study explores changes in gene expression associated with the transition of Brugia malayi third stage larvae (BmL3) from mosquitoes into mammalian hosts and how these changes are affected by radiation. Radiation effects are especially interesting because irradiated L3 induce partial immunity to filarial infections. The underlying molecular mechanisms responsible for the efficacy of such vaccines are unkown. Results: Expression profiles were obtained using a new filarial microarray with 18, 104 64-mer elements. 771 genes were identified as differentially expressed in two-way comparative analyses of the three L3 types. 353 genes were up-regulated in mosquito L3 (L3i) relative to cultured L3 (L3c). These genes are important for establishment of filarial infections in mammalian hosts. Other genes were up-regulated in L3c relative to L3i (234) or irradiated L3 (L3ir) (22). These culture-induced transcripts include key molecules required for growth and development. 165 genes were up-regulated in L3ir relative to L3c; these genes encode highly immunogenic proteins and proteins involved in radiation repair. L3ir and L3i have similar transcription profiles for genes that encode highly immunogenic proteins, antioxidants and cuticle components. Conclusion: Changes in gene expression that normally occur during culture under conditions that support L3 development and molting are prevented or delayed by radiation. This may explain the enhanced immunogenicity of L3ir. Gene Ontology and KEGG analyses revealed altered pathways between L3 types. Energy and "immune pathways" are up-regulated and may be needed for L3i invasion and survival, while growth and development are priorities for L3c. This study has improved our understanding of molecules involved in parasite invasion and immune evasion, potential targets of protective immunity, and molecules required for parasite growth and development

    Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis

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    Numerous guidelines have been developed over the past decade regarding treatments for Posttraumatic stress disorder (PTSD). However, given differences in guideline recommendations, some uncertainty exists regarding the selection of effective PTSD therapies. The current manuscript assessed the efficacy, comparative effectiveness, and adverse effects of psychological treatments for adults with PTSD. We searched MEDLINE, Cochrane Library, PILOTS, Embase, CINAHL, PsycINFO, and the Web of Science. Two reviewers independently selected trials. Two reviewers assessed risk of bias and graded strength of evidence (SOE). We included 64 trials; patients generally had severe PTSD. Evidence supports efficacy of exposure therapy (high SOE) including the manualized version Prolonged Exposure (PE); cognitive therapy (CT), cognitive processing therapy (CPT), cognitive behavioral therapy (CBT)-mixed therapies (moderate SOE); eye movement desensitization and reprocessing (EMDR) and narrative exposure therapy (low-moderate SOE). Effect sizes for reducing PTSD symptoms were large (e.g., Cohen's d ~-1.0 or more compared with controls). Numbers needed to treat (NNTs) were <4 to achieve loss of PTSD diagnosis for exposure therapy, CPT, CT, CBT-mixed, and EMDR. Several psychological treatments are effective for adults with PTSD. Head-to-head evidence was insufficient to determine these treatments' comparative effectiveness, and data regarding adverse events was absent from most studies

    A new in vitro assay measuring direct interaction of nonsense suppressors with the eukaryotic protein synthesis machinery [preprint]

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    Nonsense suppressors (NonSups) treat premature termination codon (PTC) disorders by inducing the selection of near cognate tRNAs at the PTC position, allowing readthrough of the PTC and production of full-length protein. Studies of NonSup-induced readthrough of eukaryotic PTCs have been carried out using animals, cells or crude cell extracts. In these studies, NonSups can promote readthrough directly, by binding to components of the protein synthesis machinery, or indirectly, by inhibiting nonsense-mediated mRNA decay or by other mechanisms. Here we utilize a highly-purified in vitro system (Zhang et al., 2016. eLife 5: e13429) to measure exclusively direct NonSup-induced readthrough. Of 17 previously identified NonSups, 13 display direct effects, apparently via at least two different mechanisms. We can monitor such direct effects by single molecule FRET (smFRET). Future smFRET experiments will permit elucidation of the mechanisms by which NonSups stimulate direct readthrough, aiding ongoing efforts to improve the clinical usefulness of NonSups

    Triangle Interprofessional Partners for Prevention (TIPP): Students Collaborating to Improve Care for Superutilizer Patients

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    Background: • In the US, 5% of Medicaid patients account for nearly half of health care costs, but this spending does not improve patient outcomes. • Cost-effectiveness and value are an increasing focus in health care; therefore these so-called superutilizer (SU) patients are garnering increased national attention, through the initiatives of Camden Coalition. • Interdisciplinary care can improve care for patients, but medical education often neglects these interprofessional (IP) experiences. • Triangle Interprofessional Partners for Prevention (TIPP) was established with a way to improve SU patient care, decrease hospitalization costs, and promote IP education among students in health care fields. Objectives: 1. Develop sustainable processes to engage IP students in improving quality of health care. 2. Decrease unnecessary hospitalizations and Emergency Department visits for SU patients, lowering total hospital charges. 3. Increase opportunities for IP students to collaborate, fostering mutual understanding and respect. Methods: • An EMR-generated algorithm identified SU patients at UNC (>3 hospitalizations in 12 months). • IP teams of 2-3 social work, nursing, public health, and medicine students conducted home visits and appointments to identify root causes of hospitalizations. Teams worked closely with patients to address risk factors for readmission and coordinate care. • Students met weekly with IP faculty to discuss patient needs and progress. Examples of services provided to patients include: assistance with food insecurity and unstable housing, arranging a new primary care physician, facilitating application for financial assistance with medical bills. Results: • Recruitment is ongoing, but preliminary results for patients enrolled in 2016 are available. • Of the seven enrolled patients, pre-intervention average monthly inpatient charges ranged from 2,235to2,235 to 19,662 monthly. Pre-intervention average monthly outpatient charges ranged from 0to0 to 6,457. • Post-intervention, average monthly inpatient cost decreased in five of seven patients. For these patients, average monthly inpatient charges ranged from 0to0 to 50,267 and outpatient charges ranged from 85to85 to 5,290. Three of seven patients have not had any additional hospitalizations post-intervention. Five of seven patients had a decrease in average hospitalization rate. • Results last updated February 2017 Key Lessons for Dissemination: To support other programs who wish to adapt this model at their home institutions, we summarize these key lessons for implementation: o Identifying and Connecting with Patients • During the course of our program, we trialed models including inpatient, outpatient, and a mixed patient populations, balancing SU needs with logistical necessities. It was easiest for us to successfully make contact with hospitalized patients, thus we favor an inpatient population model. If we were unable to connect with hospitalized patients before discharge, we established initial contact with patients over the phone. • We initially experienced challenges identifying hospitalized patients and assigning available team members in real time. A team member with protected time to identify patients is ideal. o IP Education and Collaboration • The divergent schedules of IP students presented challenges in finding a consistent time to meet as a large team. We propose identifying a weekly IP half day set aside by all schools for IP activities. • Successful implementation of IP initiatives requires institutional buy-in and administrative support. Our enthusiastic and supportive IP faculty champions have been essential to the TIPP’s success. o Students as significant contributors to care • We believe this program is mutually beneficial to student and patient and demonstrates the students’ potential to directly improve patient care. • Students are low cost contributors to care. TIPP’s cost of implementation consists solely of faculty time contributed to meeting with students. o Sustainability • TIPP is currently run by faculty and student volunteers. As we continue to grow, incorporating students from other professional schools, and as UNC transitions to a Next Generation Accountable Care Organization, institutional buy-in will be key to future sustainability. Conclusion: • As high value care becomes an increasing focus, addressing these SU patients is an important strategy to improve the quality and efficiency of health care. • TIPP is a student-driven organization aiming to improve the quality and efficiency of SU patient care and promote IP education. • Students work in IP teams to address SU patients’ risk factors for rehospitalization. • IP educational opportunities are an important way to develop quality interdisciplinary care givers in the future. • Results from patients recruited last year demonstrate that five of seven enrolled patients had a decrease in average monthly inpatient cost and average hospitalization rate after enrollment in the TIPP program. • Patient recruitment is ongoing and as we continue to refine our processes, we hope to include additional IP students from the schools of pharmacy and physician assistants. • Students are an abundant, untapped resource in academic medical centers and a potentially significant contributor to improve the quality and efficiency of patient care

    Views of institutional leaders on maintaining humanism in today’s practice

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    Objective To explore leadership perspectives on how to maintain high quality efficient care that is also person-centered and humanistic. Methods The authors interviewed and collected narrative transcripts from a convenience sample of 32 institutional healthcare leaders at seven U.S. medical schools. The institutional leaders were asked to identify factors that either promoted or inhibited humanistic practice. A subset of authors used the constant comparative method to perform qualitative analysis of the interview transcripts. They reached thematic saturation by consensus on the major themes and illustrative examples after six conference calls. Results Institutional healthcare leaders supported vision statements, policies, organized educational and faculty development programs, role modeling including their own, and recognition of informal acts of kindness to promote and maintain humanistic patient-care. These measures were described individually rather than as components of a coordinated plan. Few healthcare leaders mentioned plans for organizational or systems changes to promote humanistic clinician-patient relationships. Conclusions Institutional leaders assisted clinicians in dealing with stressful practices in beneficial ways but fell short of envisaging systems approaches that improve practice organization to encourage humanistic care
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