‘It’s like I have this weird superpower’: experiences of detectable and undetectable viral load among a cohort of recently diagnosed people living with HIV.

Background: By reducing HIV viral load to undetectable levels, HIV treatment slows disease progression and eliminates the possibility of sexual transmission. The promotion of undetectable viral load has also been accompanied by expectations of reducing HIV-related stigma, including self-stigma. Drawing on accounts of people recently diagnosed with HIV, we explored experiences of both detectable and undetectable viral load. Methods: Between January 2019 and November 2021, semi-structured interviews were conducted with 35 people living with HIV (PLHIV) who had received an HIV diagnosis in Australia from 2016 onward. Of these participants, 24 completed follow-up interviews approximately 12 months later. Interviews were transcribed verbatim, entered into NVivo (software v12), and thematically analysed. Results: Reflecting on the period in which their viral load was detectable, some participants described feeling ‘dirty,’ ‘viral,’ and ‘a risk’ to sexual partners. During this period, some participants minimised or ceased having sex, sometimes despite being in ongoing romantic relationships. Reaching undetectable viral load was commonly characterised as an important goal in HIV care and signalled a marker of good health and enabled a return to sexual relationships. However, the psychosocial benefits of undetectable viral load were not universally experienced, with some participants highlighting ongoing challenges of living with HIV long term. Conclusions: Increasing awareness of the benefits of undetectable viral load is an important and powerful tool for improving the health and wellbeing of PLHIV; however, the period in which one’s HIV viral load is detectable can be challenging, particularly as feelings of being ‘unclean’ and ‘a risk’ may be internalised. Ensuring PLHIV are appropriately supported during periods of viral detectability is necessary

Patient-centred approaches to providing care at HIV diagnosis: perspectives from healthcare and peer-support workers

Background. Early uptake of HIV treatment among those newly diagnosed with HIV can improve individual health and prevent onward transmission. Patient-centred care is considered an important aspect in health care, the management of HIV, and can improve uptake of and adherence to HIV treatments. Methods. Semi-structured interviews were conducted with sexual health clinicians (n, 10) and HIV support workers (n, 4) to understand how they approached HIV diagnosis delivery and care immediately thereafter. Results. Our thematic analysis identified three themes: (1) centring patient needs at diagnosis; (2) assessing patients’ readiness to begin treatment; and (3) referrals to psychosocial support services. Our findings highlight centring patients was an important aspect of how participants delivered HIV diagnoses. By taking this approach, clinicians were best able to consider patient readiness to initiate treatment and referrals to social support services. Conclusions. Given HIV diagnoses are increasingly occurring in generalist health services, our findings offer an important opportunity to learn from the experiences of specialist sexual health clinicians and HIV support workers

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

Progress towards a public chemogenomic set for protein kinases and a call for contributions

Protein kinases are highly tractable targets for drug discovery. However, the biological function and therapeutic potential of the majority of the 500+ human protein kinases remains unknown. We have developed physical and virtual collections of small molecule inhibitors, which we call chemogenomic sets, that are designed to inhibit the catalytic function of almost half the human protein kinases. In this manuscript we share our progress towards generation of a comprehensive kinase chemogenomic set (KCGS), release kinome profiling data of a large inhibitor set (Published Kinase Inhibitor Set 2 (PKIS2)), and outline a process through which the community can openly collaborate to create a KCGS that probes the full complement of human protein kinases

Urgent issues and prospects at the intersection of culture, memory, and witness interviews: Exploring the challenges for research and practice

The pursuit of justice increasingly relies on productive interactions between witnesses and investigators from diverse cultural backgrounds during investigative interviews. To date, the role of cultural context has largely been ignored by researchers in the field of investigative interviewing, despite repeated requests from practitioners and policymakers for evidence-based guidance for the conduct of interviews with people from different cultures. Through examining cultural differences in human memory and communication and considering specific contextual challenges for investigative interviewing through the lens of culture, this review and associated commentaries highlight the scope for considering culture and human diversity in research on, and the practice of, investigative interviewing with victims, witnesses, and other sources. Across 11 commentaries, contributors highlight the importance of considering the role of culture in different investigative interviewing practices (e.g., rapport building, questioning techniques) and contexts (e.g., gender-based violence, asylum seeking, child abuse), address common areas of cultural mismatch between interviewer–interviewee expectations, and identify critical future routes for research. We call for an increased focus in the investigative interviewing literature on the nature and needs of our global community and encourage constructive and collaborative discussion between researchers and practitioners from around the world to better identify specific challenges and work together towards evidence-based solutions

The Kinase Chemogenomic Set (KCGS): an open science resource for kinase vulnerability identification

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens

The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification

Abstract We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens

The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens