19 research outputs found

    Men’s perceptions of treatment as prevention in South Africa: Implications for engagement in HIV care and treatment

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    While South Africa provides universal access to treatment, HIV testing and antiretroviral therapy (ART) uptake remains low, particularly among men. Little is known about community awareness of the effects of treatment on preventing transmission, and how this information might impact HIV service utilization. This qualitative study explored understandings of treatment as prevention (TasP) among rural South African men. Narratives emphasized the known value of ART for individual health, but none were aware of its preventive effects. Many expressed that preventing transmission to partners would incentivize testing, earlier treatment, and adherence in the absence of symptoms, and could reduce the weight of a diagnosis. Doubts about TasP impacts on testing and care included enduring risks of stigma and transmission. TasP information should be integrated into clinic-based counseling for those utilizing services, and community-based education for broader reach. Pairing TasP information with alternative testing options may increase engagement among men reluctant to be seen at clinics

    KDEL Receptor 1 Contributes to Cell Surface Association of Protein Disulfide Isomerases

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    Background/Aims: Endoplasmic reticulum (ER)-resident proteins with a C-terminal KDEL ER-retention sequence are captured in the Golgi apparatus by KDEL receptors (KDELRs). The binding of such proteins to these receptors induces their retrograde transport. Nevertheless, some KDEL proteins, such as Protein Disulfide Isomerases (PDIs), are found at the cell surface. PDIs target disulfide bridges in the extracellular domains of proteins, such as integrins or A Disintegrin And Metalloprotease 17 (ADAM17) leading to changes in the structure and function of these molecules. Integrins become activated and ADAM17 inactivated upon disulfide isomerization. The way that PDIs escape from retrograde transport and reach the plasma membrane remains far from clear. Various mechanisms might exist, depending on whether a local cell surface association or a more global secretion is required. Methods: To get a more detailed insight in the transport of PDIs to the cell surface, methods such as cell surface biotinylation, flow cytometric analysis, immunoprecipitation, fluorescence microscopy as well as labeling of cells with fluorescence labled recombinant PDIA6 was performed. Results: Here, we show that the C-terminal KDEL ER retention sequence is sufficient to prevent secretion of PDIA6 into the extracellular space but is mandatory for its association with the cell surface. The cell surface trafficking of PDIA1, PDIA3, and PDIA6 is dependent on KDELR1, which travels in a dynamic manner to the cell surface. This transport is assumed to result in PDI cell surface association, which differs from PDI inducible secretion into the extracellular space. Distinct PDIs differ in their trafficking properties. Endogenous KDELR1, detectable at the cell surface, might be involved not only in the transport of cell-surface-associated PDIs, but also in their retrieval and internalization from the extracellular space. Conclusion: Beside their ER retention motive PDIs travel to the cell surface. Here they target different proteins to render their function. To escape the ER PDIs travel via various pathways. One of them depends on the KDELR1, which can transport its target to the cell surface, where it is to be expected to release its cargo in close vicinity to its target molecules. Hence, the KDEL sequence is needed for cell surface association of PDIs, such as PDIA6

    Neurology

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    Of 85 patients with ALS, the authors identified 3 patients with balanced translocations and 2 patients with pericentric inversions, all affecting distinct chromosomal loci. The high rate of constitutional aberrations (5.9%) suggests that ALS is, in part, associated with recombination-based rearrangements of genomic sequences

    The People Living with HIV (PLHIV) Resilience Scale: Development and validation in three countries in the context of the PLHIV Stigma Index

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    Supporting resilience among people living with HIV (PLHIV) is crucial to their sustained uptake of HIV services as well as psychological and social wellbeing. However, no measures exist to assess resilience specifically in relation to living with HIV. We developed the PLHIV Resilience Scale and evaluated its performance in surveys with 1207 PLHIV in Cameroon, Senegal and Uganda as part of the PLHIV Stigma Index—the most widely used tool to track stigma and discrimination among PLHIV worldwide. Factor analyses demonstrated satisfactory psychometric properties and reliability (alphas = 0.81–0.92). Levels of resilience (e.g., whether one’s self-respect has been positively, negatively, or not affected by one’s HIV status) varied substantially within and across countries. Higher resilience was associated with less depression in each country (all p \u3c 0.001), and, in Cameroon and Uganda, better self-rated health and less experience of stigma/discrimination (all p \u3c 0.001). The final 10-item PLHIV Resilience Scale can help inform interventions and policies

    High rate of constitutional chromosomal rearrangements in apparently sporadic ALS

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    Of 85 patients with ALS, the authors identified 3 patients with balanced translocations and 2 patients with pericentric inversions, all affecting distinct chromosomal loci. The high rate of constitutional aberrations (5.9%) suggests that ALS is, in part, associated with recombination-based rearrangements of genomic sequences

    Men\u27s perceptions of treatment as prevention in South Africa: Implications for engagement in HIV care and treatment

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    While South Africa provides universal access to treatment, HIV testing and antiretroviral therapy (ART) uptake remains low, particularly among men. Little is known about community awareness of the effects of treatment on preventing transmission, and how this information might impact HIV service utilization. This qualitative study explored understandings of treatment as prevention (TasP) among rural South African men. Narratives emphasized the know value of ART for individual health, but none were aware of its preventive effects. Many expressed that preventing transmission to partners would incentivize testing, earlier treatment, and adherence in the absence of symptoms, and could reduce the weight of a diagnosis. Doubts about TasP impacts on testing and care included enduring risks of stigma and transmission. TasP information should be integrated into clinic-based counseling for those utilizing services, and community-based education for broader reach. Pairing TasP information with alternative testing options may increase engagement among men reluctant to be seen at clinics
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