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Nadim Malik, Kelly A Farrell, Sarah B Withers, Elizabeth J Wright, Cathy M HoltInstitute for Cardiovascular Science, University of Manchester, Manchester, United KingdomBackground: The early stages of left ventricular (LV) dysfunction account for a much larger proportion of the population with heart disease than that with clinical heart failure. However, LV dysfunction is more difficult to diagnose than established heart failure, and because of this it is not usually treated. Research on LV dysfunction is commonly conducted in small animal models in which the cardiac pathophysiology is dissimilar to that in humans, thereby restricting translation. This study aimed to use a novel pig model of mild to moderate early ischemic LV dysfunction to assess the effects of such dysfunction in the myocardium.Methods: Multiple areas of controlled microinfarcts were created via microembolization using embolization beads, with invasive hemodynamic and transthoracic echocardiographic assessment of LV function. Four weeks after intervention, the hearts were explanted for determination of the infarcted surface area and analysis of calcium regulatory proteins.Results: In vivo hemodynamic measurements confirmed a >25% decrease in LV dP/dt (maximum and minimum) with creation of microinfarcts compared with baseline, whilst echocardiography showed mild to moderate LV dysfunction. Perioperative mortality was 10%–15%. In surviving pigs, morphometry at 4 weeks confirmed that up to 20% of the total LV surface area contained microinfarcts. Western blot analysis showed alterations in levels of the calcium regulatory proteins, sarcoplasmic reticulum Ca2+ ATPase and sodium-calcium exchange, in infarcted areas, compared with normal LV tissue from the same animals.Conclusion: These results demonstrate the usefulness of this model for investigation of the precise molecular and cellular changes associated with early mild to moderate LV dysfunction from ischemic injury, and its potential use for modulating these changes with the aim of achieving functional reversibility or regeneration of the myocardium.Keywords: left ventricular dysfunction, heart failure, porcine model

ObjectivesWe describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/μL.MethodsIn a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores  500 cells/μL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.

ObjectivesWe describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/μL.MethodsIn a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores  500 cells/μL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.

Background: The relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown.Methods: In a prospective, observational cohort of persons with acute or early HIV-1 infection, we determined the trajectory of CD4+ counts over a 48-month period in partially overlapping study sets: study set 1 included 384 participants during the time window in which they were not receiving ART and study set 2 included 213 participants who received ART soon after study entry or sometime thereafter and had a suppressed plasma HIV viral load. We investigated the likelihood and rate of CD4+ T-cell recovery to 900 or more cells per cubic millimeter within 48 months while the participants were receiving viral-load-suppressive ART.Results: Among the participants who were not receiving ART, CD4+ counts increased spontaneously, soon after HIV-1 infection, from the level at study entry (median, 495 cells per cubic millimeter; interquartile range, 383 to 622), reached a peak value (median, 763 cells per cubic millimeter; interquartile range, 573 to 987) within approximately 4 months after the estimated date of infection, and declined progressively thereafter. Recovery of CD4+ counts to 900 or more cells per cubic millimeter was seen in approximately 64% of the participants who initiated ART earlier (≤4 months after the estimated date of HIV infection) as compared with approximately 34% of participants who initiated ART later (>4 months) (P<0.001). After adjustment for whether ART was initiated when the CD4+ count was 500 or more cells per cubic millimeter or less than 500 cells per cubic millimeter, the likelihood that the count would increase to 900 or more cells per cubic millimeter was lower by 65% (odds ratio, 0.35), and the rate of recovery was slower by 56% (rate ratio, 0.44), if ART was initiated later rather than earlier. There was no association between the plasma HIV RNA level at the time of initiation of ART and CD4+ T-cell recovery.Conclusions: A transient, spontaneous restoration of CD4+ T-cell counts occurs in the 4-month time window after HIV-1 infection. Initiation of ART during this period is associated with an enhanced likelihood of recovery of CD4+ counts. (Funded by the National Institute of Allergy and Infectious Diseases and others.). [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) level is typically used as a dichotomous test for prostate cancer, resulting in overdiagnosis for a substantial number of men. The rate at which serum PSA levels change (PSA velocity) may be an important indicator of the presence of life-threatening disease.Methods: PSA velocity was determined in 980 men (856 without prostate cancer, 104 with prostate cancer who were alive or died of another cause, and 20 who died of prostate cancer) who were participants in the Baltimore Longitudinal Study of Aging for up to 39 years. The relative risks (RRs) of prostate cancer death and prostate cancer-specific survival stratified by PSA velocity were evaluated in the three groups of men by Cox regression and Kaplan-Meier analyses. Statistical tests were two-sided.Results: PSA velocity measured 10-15 years before diagnosis (when most men had PSA levels below 4.0 ng/mL) was associated with cancer-specific survival 25 years later; survival was 92% (95% confidence interval [CI] = 84% to 96%) among men with PSA velocity of 0.35 ng/mL per year or less and 54% (95% CI = 15% to 82%) among men with PSA velocity above 0.35 ng/mL per year (P<.001). Furthermore, men with PSA velocity above 0.35 ng/mL per year had a higher relative risk of prostate cancer death than men with PSA velocity of 0.35 ng/mL per year or less (RR = 4.7, 95% CI = 1.3 to 16.5; P = .02); the rates per 100,000 person-years were 1240 for men with a PSA velocity above 0.35 ng/mL per year and 140 for men with a PSA velocity of 0.35 ng/mL per year or less.Conclusions: PSA velocity may help identify men with life-threatening prostate cancer during a period when their PSA levels are associated with the presence of curable disease. [ABSTRACT FROM AUTHOR]

Cyanobacteria produce diverse classes of toxins including microcystins, nodularins, anatoxins, cylindrospermopsins and saxitoxins, encompassing a range of chemical properties and mechanisms of toxicity. Comprehensive analysis of these toxins in cyanobacterial, environmental and biological samples generally requires multiple methods of extraction and analysis. In this work, a method was developed for the major classes of cyanotoxins, which comprised of a three-step liquid-solid extraction method using 75 % CH 3 CN with 0.1 % HCOOH and a hydrophilic interaction liquid chromatography (HILIC) elution gradient that provided retention of the less polar microcystins through to the highly polar saxitoxins. Detection was performed by tandem mass spectrometry in selected reaction monitoring mode with positive and negative polarity switching. Identification criteria included matching retention times and product ion ratios with available standards. In-house validation demonstrated good performance of the method including precision ranging from 1.5 (microcystin-LA) to 5.8 (gonyautoxin-2) % RSDs, and detection limits ranging from 0.01 (cylindrospermopsin) to 0.99 (gonyautoxin-3) µg/g in freeze dried material cyanobacteria. Recovery was assessed using spiked non-toxic cyanobacterial samples (Aphanizomenon sp.) and ranged from 83 (neosaxitoxin) to 107 % ([Dha 7 ]microcystin-LR). As a demonstration of application, toxin profiles in cyanobacterial cultures, benthic and planktonic cyanobacteria field samples, and shellfish reference materials were successfully evaluated. The procedure is also amenable for extension to other polar toxin classes including domoic acid and guanitoxin. With increasing reports of cyanobacterial blooms globally, the method represents a powerful quantitative screening tool for measuring cyanotoxins across a broad range of samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Artificial urinary sphincter (AUS) placement remains the gold-standard treatment for post-prostatectomy urinary incontinence (PPUI), despite their need for periodic surgical revision., Objective: To understand the experiences of patients who undergo repeat AUS revisions., Design: Mixed design including quantitative surveys and qualitative interviews for thematic analysis., Methods: Men with ⩾2 revisions were collected from a single-institution, retrospective database of AUS patients. Participants were interviewed about their prostatectomy, incontinence, AUS placement, and revisions. A survey was administered utilizing validated tools (e.g., Decision Regret Scale (DRS), Incontinence Impact Questionnaire-7) for quantitative analysis. Interview transcripts were used for qualitative thematic analysis., Results: Of 26 respondents, 20 completed the interview. Twenty-three men completed the survey. The mean DRS score for prostatectomy was 24 (standard deviation (SD) = 27), indicating low regret. Median Incontinence Impact Questionnaire score was 54 (SD = 27), with 70% of participants describing their PPUI as "severe." Participants experienced a significant decrease in daily pad usage with AUS placement (5.5 pre-AUS vs 1.4 post-AUS, p  < 0.0001). Qualitative analysis revealed themes involving prostatectomy urgency, physician-patient relationships, expectation setting, and quality of follow-up. Most participants (96%) were satisfied with their initial AUS placement and endorsed a positive relationship with their urologist. However, 22% of participants were unaware of device limitations, including the need for revision. Some participants (26%) were uncertain of the status of their AUS, while some participants (35%) desired improved follow-up., Conclusions: Initial improvement and positive experiences with urologists motivate patients to undergo AUS repeat revision. Urologists should emphasize the limitations of the AUS before placement and follow up with patients to evaluate their needs for future care., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Introduction: HIV preexposure prophylaxis (PrEP) is highly effective at preventing HIV. We aimed to assess mental and physical health among long-term PrEP users in Australia's X-PLORE cohort., Methods: In early 2021, 1485 X-PLORE participants were emailed a survey covering demographics, sexual practices, ongoing PrEP use, physical and psychological diagnoses received since commencing PrEP, substance use, and impacts of the COVID-19 pandemic. Current anxiety and depression were assessed using GAD-7 and PHQ-9 questionnaires., Results: Of 476 participants (completion rate 32.1%), 99.8% were cis-gender men. Median PrEP use duration was 48 months (2002 person-years), with 81.7% currently using PrEP. PrEP-related toxicity was uncommon: 2.9% reported bone fractures, 1.3% low bone density, and 4.0% reported kidney problems, largely not necessitating PrEP cessation. Most (92.0%) rated their health as 'good' to 'excellent', and 22.6% reported improved health since starting PrEP, often because of improved mental health. Only 6.2% reported deterioration in health since starting PrEP, largely unrelated to PrEP. The most common diagnoses were hypertension (9.9%), depression (13.2%) and anxiety (14.9%); 17% had PHQ-9 scores indicating current moderate-to-severe depression, which was associated with unemployment [adjusted odds ratio (aOR) 3.90], regular cannabis use (aOR 2.49), and having ceased PrEP (aOR 2.13)., Conclusion: Among long-term PrEP users, of which over 80% were currently using PrEP, self-reported PrEP toxicity was uncommon. With almost one in five PrEP users categorized as having depression, and with higher risk among those having ceased PrEP, we recommend routine screening for depression and anxiety in PrEP users and corresponding follow-up of patients no longer attending for PrEP., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Patients may remain catheterized after artificial urinary sphincter surgery to prevent urinary retention, despite a lack of evidence to support this practice. Our study aims to evaluate the feasibility of outpatient, catheter-free continence surgery using a multi-institutional database. We hypothesize that between catheterized controls and patients without a catheter, there would be no difference in the rate of urinary retention or postoperative complications., Materials and Methods: We conducted a retrospective review of patients undergoing first-time artificial urinary sphincter placement from 2009-2021. Patients were stratified by postoperative catheter status into either no-catheter (leaving the procedure without a catheter) or catheter (postoperative indwelling catheter for ∼24 hours). The primary outcome, urinary retention, was defined as catheterization due to subjective voiding difficulty or documented postvoid residual over 250 mL., Results: Our study identified 302 catheter and 123 no-catheter patients. Twenty (6.6%) catheter and 9 (7.3%) no-catheter patients developed urinary retention ( P = .8). On multivariable analysis, controlling for age, cuff size, radiation history and surgeon, there was no statistically significant association between omitting a catheter and urinary retention (OR: 0.45, 95% CI: 0.13-1.58; P = .2). Furthermore, at 30 months follow-up, Kaplan-Meier survival analysis revealed that device survival was 70% (95% CI: 62%-76%) vs 69% (95% CI: 48%-82%) for the catheter and no-catheter group, respectively., Conclusions: In our multi-institutional cohort, overall retention rates were low (7%) in groups with a catheter and without. Obviating postoperative catheterization facilitates outpatient incontinence surgery without altering reoperation over medium-term follow-up.

Azaspiracids (AZAs) are a group of polyether marine algal toxins known to accumulate in shellfish, posing a risk to human health and the seafood industry. Analysis of AZAs is typically performed using LC-MS, which can suffer from matrix effects that significantly impact the accuracy of measurement results. While the use of isotopic internal standards is an effective approach to correct for these effects, isotopically labelled standards for AZAs are not currently available. In this study, 18 O-labelled AZA1, AZA2, and AZA3 were prepared by reaction with H 2 18 O under acidic conditions, and the reaction kinetics and sites of incorporation were studied using LC-HRMS/MS aided by mathematical analysis of their isotope patterns. Analysis of the isotopic incorporation in AZA1 and AZA3 indicated the presence of four exchangeable oxygen atoms. Excessive isomerization occurred during preparation of 18 O-labelled AZA2, suggesting a role for the 8-methyl group in the thermodynamic stability of AZAs. Neutralized mixtures of 18 O-labelled AZA1 and AZA3 were found to maintain their isotopic and isomeric integrities when stored at -20 °C and were used to develop an isotope-dilution LC-MS method which was applied to reference materials of shellfish matrices containing AZAs, demonstrating high accuracy and excellent reproducibility. Preparation of isotopically labelled compounds using the isotopic exchange method, combined with the kinetic analysis, offers a feasible way to obtain isotopically labelled internal standards for a wide variety of biomolecules to support reliable quantitation., (© 2023. Crown.)

Background: In mid-2022, a global mpox (formerly 'monkeypox') outbreak affecting predominantly gay and bisexual men emerged in non-endemic countries. Australia had never previously recorded mpox cases and there was no prior research on knowledge or attitudes to mpox among gay and bisexual men across Australia., Methods: We conducted a national, online cross-sectional survey between August 2022 and September 2022. Participants were recruited through community organisation promotions, online advertising, and direct email invitations. Eligible participants were gay, bisexual or queer; identified as male (cisgender or transgender) or non-binary; aged 16years or older; and lived in Australia. The main outcome measures were: knowledge and concern about mpox; recognition of mpox symptoms and transmission routes; vaccination history; acceptability of behavioural changes to reduce mpox risk, and willingness to be vaccinated., Results: Of 2287 participants, most participants were male (2189/2287; 95.7%) and gay (1894/2287; 82.8%). Nearly all had heard about mpox (2255/2287; 98.6%), and the majority were concerned about acquiring it (1461/2287; 64.4%). Most of the 2268 participants not previously diagnosed with mpox correctly identified skin lesions (2087; 92%), rash (1977; 87.2%), and fever (1647; 72.6%) as potential symptoms, and prolonged and brief skin-to-skin contact as potential ways to acquire mpox (2124, 93.7%; and 1860, 82%, respectively). The most acceptable behavioural changes were reducing or avoiding attendance at sex parties (1494; 65.9%) and sex-on-premises venues (1503; 66.4%), and having fewer sexual partners (1466; 64.6%). Most unvaccinated and undiagnosed participants were willing to be vaccinated (1457/1733; 84.1%)., Conclusions: People at risk of mpox should be supported to adopt acceptable risk reduction strategies during outbreaks and to seek vaccination.

The emergency phase of the coronavirus disease 2019 (COVID-19) pandemic is over. Still, the work goes on in understanding the SARS-CoV-2 virus and its evolution, infection impacts - acute and long term - as well as therapeutics and the lessons for preventing and responding to future pandemics. Research into the long-term post-infection effects and therapeutic interventions also expands as the post-infection period lengthens. We provide an overview of the leading edge of COVID-19 research across clinical, epidemiological and social domains., Competing Interests: CB declares honorarium from Novavax as part of the Australian Vaccine Advisory Group; acting as an expert witness on a range of legal cases relating to the pandemic and other epidemiological matters; and payment from Moderna for presenting on COVID-19 issues. BR is employed by the ASHM, which convened the Australasian COVID-19 Conference 2023. SM reports a grant from the Health Research Council of New Zealand for participation in ASCOT and REMAP-CAP trials for COVID-19 treatment; was a member of the Therapeutics Advisory Group to the New Zealand Ministry of Health and a member of the NZ national guidelines writing group for COVID-19. KH reports a grant and consulting fees/honorarium from Gilead Sciences and consulting fees and travel support from Moderna to attend meetings.

Background: Gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) are at increased risk for sexually transmissible infections. Hepatitis C virus (HCV) risk among PrEP users is less clear. We explored HCV prevalence and incidence among cohorts of gay and bisexual men using PrEP and sources of heterogeneity across studies., Methods: This was a systematic review and meta-analysis of open-label PrEP studies to April 2022 reporting HCV prevalence at baseline or incidence during follow-up among gay and bisexual men using PrEP. Pooled prevalence and incidence estimates were calculated using random-effects meta-analysis, and subgroup analyses were performed by study- and country-level characteristics, including availability of HCV direct-acting antiviral (DAA) therapy at time of study., Results: Twenty-four studies from 9 countries were included, with a total sample of 24 733 gay and bisexual men. Pooled HCV antibody baseline prevalence was 0.97% (95% CI, 0.63%-1.31%), and pooled HCV RNA baseline prevalence was 0.38% (95% CI, 0.19%-0.56%). Among 19 studies reporting HCV incidence, incidence ranged from 0.0 to 2.93/100 person-years (py); the pooled estimate was 0.83/100py (95% CI, 0.55-1.11). HCV incidence was higher in 12 studies that began follow-up before broad DAA availability (1.27/100py) than in 8 studies that began follow-up after broad DAA availability (0.34/100py) and higher in studies in Europe compared with North America and Australia., Conclusions: Early reports of high HCV incidence among PrEP-using cohorts likely reflect enrollment of individuals based on specific risk-based eligibility criteria for smaller studies and enrollment before DAA scale-up. In contexts where both DAAs and PrEP have been implemented at scale, studies report lower HCV incidence. PrEP-specific HCV testing guidelines should be guided by local epidemiology., Competing Interests: Potential conflicts of interest. M.W.T. has received speaker's honoraria, consultancy fees, and researcher-initiated funding from Gilead Sciences unrelated to this work. E.J.W.'s institution received funding from Gilead Sciences for E.J.W.'s work on an Advisory Board and for delivering educational content. V.J.C., D.M., and E.J.W. have received research funding from ViiV health care, not related to this work. J.S.D., M.E.H., and M.A.S.'s institution has received funding for research and speaking from Gilead Sciences and AbbVie. M.A.S. has received researcher-initiated research funding from Gilead Sciences and AbbVie and consultant fees from Gilead Sciences for activities unrelated to this work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Responses to trauma are often characterized either by the presence or absence of psychological distress; however, the process of adapting after trauma also includes potential positive change. While some studies document that the majority of individuals exposed to single event terrorism report low levels of psychological distress, more research is needed to understand different adaptation profiles following this type of trauma, and the factors that might predict responses., Methods: We examined post-trauma responses in 257 first responders/medical professionals (66.8 percent) and civilians (33.2 percent) exposed to the 2013 Boston Marathon Bombings. Data for post-trauma profiles-post-traumatic growth (PTG), post-traumatic stress, and emotion regulation-and profile predictors-trauma proximity, trauma history, and coping flexibility-were collected approximately 2.5 years after the bombings. Latent profile analysis identified response profiles, and multinomial logistic regression identified demographic, event-specific, and psychological predictors of profile membership., Results: Four profiles emerged: (1) symptomatic, (2) resistant, (3) resilient, and (4) struggling growth. First responder role decreased the odds of belonging to the struggling growth profile, as compared to the symptomatic profile. Greater coping flexibility and adaptive emotion regulation increased the odds of membership in the struggling growth, rather than symptomatic profile., Conclusion: A subset of individuals experiencing post-traumatic stress symptoms years after trauma exposure may also be utilizing flexible, adaptive coping strategies and experiencing PTG. First responders may have difficulty experiencing simultaneous -distress and growth, and interventions designed to promote healthy post-trauma adaptation for this population could be tailored accordingly.

This paper hosts the first meaningful dialogue between two important epistemic movements for criminology: zemiology and decolonisation. I identify that zemiology has a disciplinary blindness to colonialism and explain this using Gurminder K. Bhambra's scholarship-and cognate scholarship-as a frame. Three cases-Pemberton's Harmful Societies, Grenfell, and Border Zemiology-are selected for their critical importance within zemiology. They are used to argue that zemiology works within a standard narrative of modernity characterised by capitalist nation-states, which does not recognise the colonial foundations of both of these. Capitalist modernity is, however, a colonial formation. Recognising this allows for a better understanding for a wide range of harms. I then discuss future directions for decolonial zemiology, advocating not for expansion of repertoire, but canonical revision so that colonialism is afforded space as an explanatory frame and zemiology can better explain social harm on a global level., (© The Author(s) 2023.)

Background: Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART., Methods: Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799, or ≥ 800 cells/mm3. After 36-44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata., Results: We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799, and 50 in the ≥ 800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600-799 or 500-599 cells/mm3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500-599 cells/mm3 (median [interquartile range]: 16.3 [7.0-117.6] vs 68.4 [13.7-213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females., Conclusions: Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600-799 or 500-599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART., Competing Interests: Potential conflicts of interest. T. A. R. has received funding from the Danish Research Council, Region Midt Denmark, The Australian Centre for HIV and Hepatitis Virology Research, Melbourne HIV Cure Consortium, and Gilead outside the submitted work and payment for lectures from Gilead Sciences. T. A. R. also reports a leadership or fiduciary role with the HIV Cure Community Partnership Steering Committee in Australia, the 18th European AIDS Conference Scientific Committee, and the Australasian Society for HIV Medicine (ASHM), Taskforce on Blood-borne Viruses (BBV), Sexual Health and COVID-19. D. P. D. was funded by a grant from the National Cancer Institute (grant number RO1-CA228172). S. P. has received funding from the National Health and Medical Research Council of Australia (NHMRC), National Institutes of Health (NIH), amFAR, the Foundation for AIDS Research, and The Australian Centre for HIV and Hepatitis Virology Research. P. M. declares that her institution received funding from the INSIGHT Network to undertake the START study and received a grant from Alfred Health to conduct sample collection and shipment for the HIV Reservoirs substudy of the START trial. C. C. declares receipt of funding from the NHMRC for an Early Career Fellowship. S. B.-F. declares that her institution received funding from the INSIGHT Network to undertake the START study. K. P. declares that she has received unconditional research grants from ViiV Healthcare and Gilead Sciences. P. P. holds shares in Gilead Sciences and GlaxoSmithKline. S. R. L. has received funding from the Australian NHMRC, the Australian Center for HIV and Hepatitis Virology Research NIH, amfAR (Magnet grant award number 19-02602), Gilead Sciences (clinical research grant), Merck, ViiV, and Leidos outside the submitted work. S. R. L. also reports consulting fees from Abivax, Geovax, ViiV, and Tetralogic, honoraria from Gilead Sciences, Bristol Myers Sqibb, and Merck Sharpe & Dohme, an International PCT patent (PCTAU2017050631), and participation on advisory boards for Abivax, Bionor, ViiV, Calimmune, InniVirVax, Aelix Therapeutics, Immunocore, and the French Agency for Research on AIDS and Viral Hepatitis (ANRS) Emerging Infectious Diseases. E. J. W. received research grants from Gilead Sciences, Merck Sharp & Dohme, and The Australian Centre for HIV and Hepatitis Virology Research for this submitted work. E. J. W. reports receipt of research grants from the Victorian, Tasmanian, and South Australian governments; E. J. W. has received free study drug from Gilead Sciences for the VicPrEP study and her institution has received funding from Gilead Sciences, ViiV Healthcare, Abbott, Merck Sharp & Dohme, Boehringer Ingelheim, and Janssen-Cilag. E. J. W. also reports payment for lectures from Gilead Sciences and the Australasian Society of HIV Medicine and participation on an Advisory Board for Gilead Sciences. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

The presence of azaspiracids (AZAs) in shellfish may cause food poisoning in humans. AZAs can accumulate in shellfish filtering seawater that contains marine dinoflagellates such as Azadinium and Amphidoma spp. More than 60 AZA analogues have been identified, of which AZA1, AZA2 and AZA3 are regulated in Europe. Shellfish matrices may complicate quantitation by ELISA and LC-MS methods. Polyclonal antibodies have been developed that bind specifically to the C-26-C-40 domain of the AZA structure and could potentially be used for selectively extracting compounds containing this substructure. This includes almost all known analogues of AZAs, including AZA1, AZA2 and AZA3. Here we report preparation of immunoaffinity chromatography (IAC) columns for clean-up and concentration of AZAs. The IAC columns were prepared by coupling polyclonal anti-AZA IgG to CNBr-activated sepharose. The columns were evaluated using shellfish extracts, and the resulting fractions were analyzed by ELISA and LC-MS. The columns selectively bound over 300 ng AZAs per mL of gel without significant leakage, and did not retain the okadaic acid, cyclic imine, pectenotoxin and yessotoxin analogues that were present in the applied samples. Furthermore, 90-92% of the AZAs were recovered by elution with 90% MeOH, and the columns could be re-used without significant loss of performance., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Overseas-born and newly arrived gay and bisexual men and men who have sex with men (GBMSM) are at higher risk of acquiring HIV in comparison to Australian-born GBMSM. Pre-exposure prophylaxis (PrEP) is subsidized by the Australian government under Medicare, Australia's universal health insurance scheme, however many members of this population are Medicare-ineligible, which could prevent them from accessing PrEP. We wanted to explore participants' knowledge of and attitudes toward PrEP and their opinions of new PrEP modalities, namely injectable PrEP and PrEP implants., Methods: We conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (<5 years in Australia) GBMSM of varying PrEP use. We asked their opinions of PrEP and their preferences of new PrEP modalities. Interviews were audio recorded and transcribed verbatim. We conducted a reflexive thematic analysis to interpret the data., Results: Participants' views reflect the intersections between systemic factors, such as Medicare ineligibility and the high cost of PrEP, with socio-cultural factors, such as lack of knowledge about PrEP, internalized stigma stemming from homo- and sex-negativity, and stigmatizing attitudes toward PrEP and PrEP users. For participants who were on PrEP, being community connected, having a positive relationship with doctors and nurses, and being informed of the option to purchase PrEP from overseas pharmacies at a low cost helped them to overcome some of these barriers. Additionally, there was a strong preference for injectable PrEP but not PrEP implants. Participants stressed the importance of providing a comprehensive information about PrEP specific to this population and to make PrEP free for all., Conclusions: We concluded that resources about PrEP specific to this population that address both systemic and socio-cultural factors are needed, and for these resources to be available in languages other than English. This is to coincide with on-going advocacy to increase the capacity of publicly funded sexual health clinics to provide multilingual PrEP services for people without Medicare, and to make PrEP free for all. These combined strategies have the potential to increase PrEP knowledge and uptake among this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sudarto, Chow, Medland, Fairley, Wright, Armishaw, Price, Phillips and Ong.)

Background: Although data from large implementation trials suggest that sexually transmissible infection (STI) risk increases among gay and bisexual men who initiate HIV pre-exposure prophylaxis (PrEP), there are few data on the trends in population-level STI incidence in the years following widespread PrEP implementation. We aimed to describe trends in bacterial STI incidence among gay and bisexual men using PrEP across Australia in the context of broad PrEP availability through Australia's subsidised medicines scheme., Methods: We analysed linked clinical data from HIV-negative gay and bisexual men aged 16 years or older who had been prescribed PrEP across a sentinel surveillance clinical network, including 37 clinics in Australia, between Jan 1, 2016, and Dec 31, 2019. Patients were included if they had STI testing at least twice during the observation period. Repeat testing methods were used to calculate chlamydia, gonorrhoea, syphilis, and any STI incidence rates during individuals' periods of PrEP use. Incidence rate ratios (IRRs) for estimated change in incidence per half calendar year (6-month) period were calculated using negative binomial regression. Secondary analyses compared STI incidence rates across individuals initiating PrEP in each year from 2016 to 2019, as well as by length of time using PrEP (per each additional 6 months of PrEP use)., Findings: 22 730 men were included in the analyses. During the observation period, 11 351 chlamydia infections were diagnosed in 6630 (30·1%) of 22 034 men over 25 991·2 person-years of PrEP use (incidence rate 43·7 cases [95% CI 42·9-44·5] per 100 person-years). Chlamydia incidence decreased from 48·7 cases per 100 person-years in July-December, 2016, to 42·0 cases per 100 person-years in July-December, 2019 (IRR for estimated change per 6-month period 0·98 [95% CI 0·97-0·99]; p=0·0031). 9391 gonorrhoea infections were diagnosed in 5885 (26·9%) of 21 845 men over 24 858·7 person-years of PrEP use (incidence rate 37·8 cases [95% CI 37·0-38·5] per 100 person-years). Gonorrhoea incidence decreased from 45·5 cases per 100 person-years in July-December, 2016, to 37·2 cases per 100 person-years in July-December, 2019 (IRR 0·97 [95% CI 0·96-0·98]; p<0·0001). Declines in chlamydia and gonorrhoea incidence were most prominent in the first 18 months of observation and incidence was stable thereafter. 2062 syphilis infections were diagnosed in 1488 (7·7%) of 19 262 men over 21 978·9 person-years of PrEP use (incidence rate 9·4 cases [95% CI 9·0-9·8] per 100 person-years). Syphilis incidence increased from 6·2 cases per 100 person-years in July-December, 2016, to 9·8 cases per 100 person-years in July-December, 2019 (IRR 1·08 [95% CI 1·05-1·10]; p<0·0001)., Interpretation: Chlamydia and gonorrhoea incidence among gay and bisexual men using PrEP were highest in the early months of PrEP implementation in Australia and stabilised at slightly lower rates thereafter following wider PrEP uptake. Lower prospective STI risk among people initiating PrEP in later years contributed to the observed trends in STI incidence. Widespread PrEP implementation can contribute to increased STI screening and detection., Funding: Australian Department of Health, National Health and Medical Research Council., Competing Interests: Declaration of interests MWT reports speakers' honoraria and investigator-initiated research grants from Gilead Sciences. RG reports research support funding from Gilead Sciences. CB reports honoraria from Gilead Sciences. EJW is the chair of the COVID-19 Taskforce of the Australasian Society of HIV, Viral Hepatitis, and Sexual Health Medicine, and reports investigator-initiated research funding from ViiV Healthcare, and consulting and travel fees from Gilead Sciences. AG reports research grants from Sequris and ViiV Healthcare, receipt of study drug from GlaxoSmithKline, and personal fees from Merck Sharp and Dohme. MEH reports investigator-initiated research grants from Gilead Sciences and Abbvie. MAS reports investigator-initiated research grants from Gilead Sciences and Abbvie and consulting fees from Gilead Sciences. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: In order to accurately characterize how a history of radiation therapy affects the lifespan of replacement artificial urinary sphincters (AUSs), all possible sources of device failure must be considered. We assessed the competing risks of device failure based on radiation history in men with replacement AUSs., Materials and Methods: We identified men who had a replacement AUS in a single institutional, retrospective database. To assess survival from all-cause device failure based on radiation history and other factors, we conducted Kaplan-Meier, Cox proportional-hazards and competing risks analyses., Results: Among 247 men who had a first replacement AUS, men with a history of radiation had shorter time to all-cause device failure (median 1.4 vs 3.5 years for men with radiation vs without radiation history, p=0.02). On multivariable Cox-proportional hazards analysis, previous radiation was associated with increased risk of all-cause device failure (HR: 2.12, 95% CI: 1.30-3.43, p=0.002) . On multivariable cause-specific hazards analysis, prior radiation was associated with a higher risk of erosion/infection (HR: 7.57, 95% CI: 2.27-25.2, p <0.001), but was not associated with risk of urethral atrophy (p=0.5) or mechanical failure (p=0.15)., Conclusions: Among men with a replacement AUS, a history of pelvic radiation was associated with shorter time to device failure of any cause. Radiation was also specifically associated with a sevenfold increase in the risk of erosion or infection of replacement AUS, but not with urethral atrophy or mechanical failure. Patients with a replacement AUS should be appropriately counseled on how radiation history may impact outcomes of future revisions.