Ending HIV Transmission in Australia: Expanding PrEP to Cisgender Women: A Scoping Review.

Pre-exposure prophylaxis (PrEP) availability through the Pharmaceutical Benefits Scheme provides real potential for the elimination of HIV transmission in Australia, as evidenced by a rapid decline in HIV incidence among gay and bisexual men (GBM). However, HIV elimination will not be possible without also extending PrEP to other populations, including cisgender women. We conducted a scoping review to examine the extent to which PrEP access for cisgender women has been considered in Australia. A comprehensive search across five databases, grey literature, and hand search of references was conducted. A single reviewer conducted title and abstract screening and two reviewers completed full-text screening and data extraction. Nineteen documents were included in the final review and included both peer-reviewed journal articles and guidelines and strategies. Focused discussion of cisgender women's use of PrEP was largely missing from the literature and, although their use of PrEP is supported in some relevant guidelines, little has been done to actively develop strategies to inform cisgender women about PrEP as a precursor to prescribing for HIV prevention. Healthcare providers' narrow view of PrEP as being the domain of GBM further limits cisgender women's potential access. If HIV elimination in Australia is to be a reality, we need to develop mechanisms to specifically engage with cisgender women about PrEP.

Hiding in plain sight: highlighting the research gap on access to HIV and other sexual health services for underrepresented gay men in developed Western countries - insights from a scoping review with a focus on Arab men.

BACKGROUND: Strategies pertaining to HIV and sexual health for gay, bisexual, and other men who have sex with men (GBMSM) have shifted focus towards underrepresented subgroups within some developed Western countries. Although emerging research exists on some subgroups, limited attention has been given to the needs of Arab GBMSM in these contexts. Considering they are part of a large diaspora, understanding their access to services is crucial. This paper focuses on Arab GBMSM as a case study within a scoping review, highlighting their hidden status within the broader landscape of HIV and sexual health research for GBMSM in the West. METHODS: A multi-method search strategy was employed, including searching four electronic databases using several terms within each of the following search topics: Arab, GBMSM, HIV and other sexual health services, and developed Western countries. RESULTS: Of the 384 articles found, only one addressed the research question and met the inclusion criteria, revealing a stark scarcity of research on access to HIV and sexual health services for this population. CONCLUSIONS: This review highlights a paucity of research on access to HIV and sexual health services for underrepresented GBMSM populations in developed Western countries. The literature indicates that, for Arab men, this may be due to a difficulty in participant recruitment and poor data collection efforts. By focusing on one hidden population, we aim to advocate for inclusive policies and interventions that promote equitable sexual health access for all. Addressing this research gap aligns with broader local and global HIV strategies to reduce disparities among underrepresented GBMSM populations.

Low incidence of advanced neurological burden but high incidence of age-related conditions that are dementia risk factors in aging people living with HIV: a data-linkage 10-year follow-up study.

Although increasing research is focusing on age-related comorbidities (ARC) among people living with HIV (PLHIV), no studies have concomitantly assessed non-HIV age-related neurological disorders (e.g., Alzheimer's dementia). A total of 254 PLHIV and 69 HIV-negative controls completed baseline medical history and cognitive testing. ARC data were collected from medical records over the subsequent 9-10 years and included all types of strokes, all types of dementia, mild cognitive impairment, Parkinson's disease, motor neuron disease (grouped into a non-HIV age-related neurological category), cardiovascular disease, chronic kidney disease, chronic liver disease, chronic lung disease, non-AIDS cancers, osteoporosis, and diabetes. Kaplan-Meier curves assessed differences in the incident rates (per 1000 person year) of groups of ARC as defined above and combined ARC (i.e., development of any of the ARC) among younger (baseline age < 50) and older (baseline age ≥ 50) PLHIV and younger and older controls. Cox-proportional hazard models assessed the individual and interaction effects of HIV status and chronological age, in addition to a range of demographic and clinical variables including historical and baseline HIV brain involvement on the risk of developing combined ARC. Older PLHIV had a higher incidence of cardiovascular disease, osteoporosis, and combined ARC compared to other groups (p < 0.05). Incident rate of non-HIV age-related neurological disorders was 2.3 [0.93, 4.79] per 1000 person year. While this incident rate was higher in older PLHIV (5.37 [1.97, 11.92]) than older HIV-negative participants (3.58 [0.18-17.67]), this was not significant. In multivariate analyses, HIV status and chronological age, but not their interaction, and smoking were associated with higher risk of combined ARC (p < 0.05). In analyses focusing on PLHIV, older age and taking abacavir/efavirenz/atazanavir/darunavir containing antiretroviral treatments at the time of diagnosis were associated with greater ARC (p < 0.05). Non-HIV age-related neurological disorders are uncommon in older PLHIV, where the majority were < 70 years of age at the end of follow-up. However, the greater burden of ARC among older PLHIV, most of which are established dementia risk factors, warrants the establishment of commensurate prevention strategies and greater attention to neurocognitive screening.

Trends in Testing and Self-Reported Diagnoses of Sexually Transmitted Infections in Gay and Bisexual Men in Australia, 2017 to 2021: Analysis of National Behavioral Surveillance Surveys.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBM) are overrepresented in diagnoses of sexually transmitted infections (STIs) relative to their population size. This study assessed trends in STI testing and diagnoses among GBM in Australia. METHODS: The Gay Community Periodic Surveys are repeated cross-sectional behavioral surveillance surveys of GBM. Participants reported the number of anal swabs, throat swabs, urine samples, and blood tests for syphilis they undertook in the last year. "Frequent comprehensive testing" was defined as ≥3 of each test in the previous year. Participants reported STI diagnoses of chlamydia, gonorrhea, syphilis, and other STIs in the last year. Trends in testing and diagnoses from 2017 to 2020 and 2020 to 2021 were assessed with logistic regression models. RESULTS: We analyzed 24,488 survey responses from participants reporting casual sex in the last 6 months. Between 2017 and 2020, frequent comprehensive STI testing decreased among HIV-negative GBM on preexposure prophylaxis (PrEP) from 71.7% to 68.9% and declined further to 58.6% in 2021. Frequent comprehensive STI testing was stable during 2017-2020 among HIV-negative/untested GBM not on PrEP (17.4%-14.6%) and HIV-positive GBM (30.4%-35.1%) but declined in 2021 to 7.5% among non-PrEP-users and 25.7% among HIV-positive participants. There were minimal changes in STI diagnoses during 2017-2020, but diagnoses declined in 2021. CONCLUSIONS: Many GBM do not meet Australian STI testing guidelines that recommend quarterly testing. Further evaluation of whether this recommendation is realistic or necessary to reduce STIs among GBM is recommended.

Adjusting Behavioural Surveillance and Assessing Disparities in the Impact of COVID-19 on Gay and Bisexual Men's HIV-Related Behaviour in Australia.

COVID-19 has disrupted sexual behaviour and access to health systems. We adapted regular HIV behavioural surveillance of gay and bisexual men (GBM) in Australia in response to COVID-19, assessed the impact on the profile of the sample, the participants' HIV-related behaviour, and whether COVID-19 may have accentuated existing disparities in the Australian HIV epidemic. Data collected from five states during July 2017-June 2021 were included (N = 31,460). The emphasis on online recruitment after COVID-19 led to smaller sample sizes, greater geographic reach, and a higher proportion of bisexual-identifying participants. Most participants (88.1%) reported physical distancing and 52.1% had fewer sex partners due to COVID-19. In the COVID-19-affected rounds (July 2020-June 2021), the number of male partners, recent HIV testing and pre-exposure prophylaxis (PrEP) use all fell, and HIV risk among the smaller group of participants who reported casual sex increased. COVID-related changes were generally more pronounced among GBM aged under 25 years, participants from suburbs with fewer gay residents, and bisexual men. These groups should be prioritised when encouraging GBM to reengage with HIV testing services and effective prevention methods, like condoms and PrEP.

RESUMEN: COVID-19 ha interrumpido el comportamiento sexual y el acceso a los sistemas de salud. Adaptamos la vigilancia regular del comportamiento de hombres homosexuales y bisexuales (GBM) hacia el VIH en Australia en respuesta a COVID-19, evaluamos el impacto en el perfil de la muestra, el comportamiento relacionado con el VIH de los participantes y si COVID-19 puede haber acentuado las existentes disparidades en la epidemia australiana de VIH. Se incluyeron los datos recopilados de cinco estados entre julio de 2017 y junio de 2021 (N = 31 460). El énfasis en el reclutamiento en línea después de COVID-19 resulto en tamaños de muestra más pequeños, mayor alcance geográfico y una mayor proporción de participantes que se identifican como bisexuales. La mayoría de los participantes (88,1%) describieron participando en el distanciamiento físico y el 52,1% tuvo menos parejas sexuales debido a la COVID-19. En las rondas afectadas por COVID-19 (julio de 2020 a junio de 2021), disminuyó la cantidad de parejas masculinas, el uso reciente de pruebas de VIH y de la profilaxis previa a la exposición (PrEP), y el riesgo de VIH entre el grupo más pequeño de participantes que participaron en sexo casual aumentó. Los cambios relacionados con COVID fueron generalmente más pronunciados entre GBM menores de 25 años, participantes de suburbios con menos residentes homosexuales y hombres bisexuales. Se debe priorizar a estos grupos al alentar a GBM a volver a comprometerse con los servicios de pruebas de VIH y métodos de prevención efectivos, como condones y PrEP.

Variations in HIV Prevention Coverage in Subpopulations of Australian Gay and Bisexual Men, 2017-2021: Implications for Reducing Inequities in the Combination Prevention Era.

Using repeated behavioural surveillance data collected from gay and bisexual men (GBM) across Australia, we assessed trends in HIV prevention coverage (the level of 'safe sex' achieved in the population by the use of effective prevention methods, including condoms, pre-exposure prophylaxis [PrEP] and having an undetectable viral load). We stratified these trends by age, country of birth/recency of arrival, sexual identity, and the proportion of gay residents in the participant's suburb. Among 25,865 participants with casual male partners, HIV prevention coverage increased from 69.8% in 2017 to 75.2% in 2021, lower than the UNAIDS target of 95%. Higher levels of coverage were achieved among older GBM (≥ 45 years), non-recently-arrived migrants, and in suburbs with ≥ 10% gay residents. The lowest levels of prevention coverage (and highest levels of HIV risk) were recorded among younger GBM (< 25 years) and bisexual and other-identified participants. Younger, recently-arrived, and bisexual GBM were the most likely to use condoms, while PrEP use was concentrated among gay men, 25-44-year-olds, and in suburbs with more gay residents. The use of undetectable viral load was most common among participants aged ≥ 45 years. Our analysis shows that high HIV prevention coverage can be achieved through a mixture of condom use, PrEP use, and undetectable viral load, or by emphasising PrEP use. In the Australian context, younger, bisexual and other-identified GBM should be prioritised for enhanced access to effective HIV prevention methods. We encourage other jurisdictions to assess the level of coverage achieved by combination prevention, and variations in uptake.

RESUMEN: Utilizando datos repetidos de vigilancia conductual recopilados de hombres homosexuales y bisexuales (GBM) en toda Australia, evaluamos las tendencias en la cobertura de la prevención del VIH (el nivel de "sexo seguro" logrado en la población mediante el uso de métodos de prevención eficaces, incluyendo condones, Profilaxis de Pre-Exposición al VIH [PrEP] y tener una carga viral indetectable). Estratificamos estas tendencias por edad, país de nacimiento/tiempo desde la llegada al país, identidad sexual y proporción de residentes homosexuales en el suburbio del participante. Entre 25.865 participantes con parejas masculinas ocasionales, la cobertura de prevención del VIH aumentó del 69,8% en 2017 al 75,2% en 2021, cifra inferior al objetivo de ONUSIDA del 95%. Se lograron niveles más altos de cobertura entre GBM de mayor edad (≥45 años), inmigrantes no llegados recientemente y en suburbios con ≥10% de residentes homosexuales. Los niveles más bajos de cobertura de prevención (y los niveles más altos de riesgo de VIH) se registraron entre los GBM más jóvenes (<25 años) y los participantes bisexuales y con otras identidades. Los GBM más jóvenes, recién llegados y bisexuales fueron los más propensos a usar condones, mientras que el uso de PrEP se concentró entre hombres homosexuales, de 25 a 44 años, y en los suburbios con más residentes homosexuales. El uso de carga viral indetectable fue más común entre los participantes de ≥45 años. Nuestro análisis demuestra que se puede lograr una alta cobertura de prevención del VIH mediante una combinación del uso de condón, uso de PrEP y carga viral indetectable, o enfatizando el uso de PrEP. En el contexto australiano, se debe dar prioridad a los GBM más jóvenes, bisexuales y con otras identidades para mejorar el acceso a métodos eficaces de prevención del VIH. Alentamos a otras jurisdicciones a evaluar el nivel de cobertura logrado mediante la prevención combinada y las variaciones en la adopción.

National Surveillance of Home-Based HIV Testing Among Australian Gay and Bisexual Men, 2018-2020: Uptake After Commercial Availability of HIV Self-Tests.

HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018-2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23-1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia's HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM.

Is sex lost in translation? Linguistic and conceptual issues in the translation of sexual and reproductive health surveys.

Translated questionnaires are increasingly used in population health research. Nevertheless, translation is often not conducted with the same rigour as the process of survey development in the original language. This has serious limitations and may introduce bias in question relevance and meaning. This article describes and reflects on the process of translating a large and complex sexual and reproductive health survey from English into Simplified Chinese. We interrogated assumptions embedded in taken-for-granted translation practice to locate the sociocultural origins of these assumptions. We discuss how terminology and expression related to sexual and reproductive health may lose their conceptual or linguistic significance during translation in three different ways. Firstly, meanings can be lost in the negotiation of meanings associated with linguacultural and geographical variations of terminology. Secondly, meanings can be lost in the clash between everyday and professional sexual and reproductive health discourses. Thirdly, meanings can be lost due to the design of the source questionnaire and the intended mode of survey administration. We discuss ways to help overcome the unavoidable translation challenges that arise in the process of translating English sexual and reproductive health surveys for migrants from non-English speaking backgrounds.

The impact of social connections and discrimination to HIV risk among Asian gay and bisexual men in Australia.

BACKGROUND: Asian gay, bisexual, and other men who have sex with men (GBMSM) are overrepresented in new HIV diagnoses in Australia. Social engagement with other GBMSM has been associated with HIV testing and pre-exposure prophylaxis (PrEP) uptake. Asian GBMSM may be socially disconnected from LGBTQ+ people, which may increase their HIV risk. This analysis assessed the contribution of social connection on HIV risk among Asian GBMSM. METHODS: Using an online cross-sectional survey of Asian GBMSM in Australia, we measured condomless anal intercourse (CLAI) in the last 6months without PrEP or an undetectable viral load (UVL), i.e. CLAI with a risk of HIV transmission. Bivariable and multivariable logistic regression models were performed to compare demographic characteristics and social engagement of participants who had CLAI without PrEP or UVL to those who had not. Analyses were restricted to participants who reported sex with casual partners in the last 6months. RESULTS: Among 509 participants who had casual partners in the last 6months, 151 (29.7%) reported CLAI without PrEP or UVL. CLAI without PrEP or UVL was negatively associated with full-time employment, and recently being tested for HIV and was positively associated with experiencing discrimination based on sexual orientation. Social engagement with LGBTQ+ people was not associated with CLAI without PrEP or UVL. CONCLUSIONS: CLAI without PrEP or UVL was not related to social connections with LGBTQ+ people but was more likely among Asian men who had experienced sexuality-related discrimination, suggesting that mitigating homophobia and biphobia may assist in improving HIV prevention among Asian GBMSM who live in Australia.

Assessing the Impact of HIV Preexposure Prophylaxis Scale-Up on Gonorrhea Incidence Among Gay and Bisexual Men in Sydney: A Mathematical Modeling Study.

BACKGROUND: The rollout of preexposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men (GBM) is associated with increases in condomless anal intercourse, potentially increasing the incidence of other sexually transmissible infections (STIs). METHODS: We developed an individual-based mathematical model to simulate the transmission of Neisseria gonorrhoeae among GBM in Sydney, accounting for changes in sexual practices, STI testing, and PrEP use. We calibrated and validated the model using reported incidence rates for HIV-positive and HIV-negative GBM from 2010 to 2019. Scenarios were run with varying PrEP uptake, PrEP-related STI testing, and PrEP-related sexual behavior and testing intervals up to 2030 to assess the impact of PrEP use on gonorrhea incidence. RESULTS: Preexposure prophylaxis uptake and associated 3-monthly STI testing from 2015 onward resulted in a predicted increase from 20 to 37 N. gonorrhoeae infections per 100 person-years among HIV-negative GBM by the end of 2020. This is lower than the counterfactual predictions of 45 per 100 person-years if PrEP were not scaled up and 48 per 100 person-years with nonadherence to 3-monthly STI testing. Increasing the time between STI tests for PrEP users by 1 month from 2018 results in the incidence rate among HIV-negative GBM increasing by 8% by 2030. If PrEP coverage doubles from 24% to 53%, incidence among HIV-negative GBM declines by ~25% by 2030. CONCLUSIONS: Behavior change due to widespread PrEP use may lead to significant increases in gonorrhea incidence in GBM, but the recommended quarterly STI testing recommended for PrEP users should reduce incidence by 18% by 2030.

Changing Levels of Social Engagement with Gay Men Is Associated with HIV Related Outcomes and Behaviors: Trends in Australian Behavioral Surveillance 1998-2020.

Changes to how gay, bisexual, and other men who have sex with men (GBM) connect with each other and with their communities have implications for HIV prevention. Social engagement with gay men (defined as having friends who are gay men and spending time with them) has been associated with HIV related outcomes over time among Australian GBM. Using data collected in national, repeated, cross-sectional surveys of GBM between 1998 and 2020 (N = 161,117), analyses of trends in the prevalence of gay social engagement (GSE) in Australia were conducted using linear regression. To assess changing associations with GSE at different time points in the HIV epidemic, three cross-sectional analyses were conducted on factors associated with high and low GSE in 1999/2000, 2009/2010, and 2019/2020 using bivariate and multivariable logistic regression. GSE (scored from 0 to 7) declined among all participants from 4.76 in 1998 to 4.04 in 2020 (p < 0.001) with a steeper decline among GBM aged under 25 years from 4.63 in 1998 to 3.40 in 2020 (p < 0.001). In all timepoints, high GSE was associated with older age, being university educated, full time employment, identifying as gay, recent HIV testing, and PrEP uptake. While mostly associated with protective behaviors, high GSE was also associated with some practices that may put GBM at risk of HIV infection such as drug-enhanced sex and group sex in the most recent timepoint. Changing levels of GSE have implications for health promotion among GBM, particularly how to engage GBM less connected to gay social networks.

Interaction of JNK and mGluR5 in the regulation of psychomotor behaviours after repeated cocaine administration.

Activation of protein kinases after cocaine administration controls psychomotor behaviours by interacting with metabotropic receptors in the brain. This study identified how c-Jun N-terminal kinase (JNK) interacts with metabotropic glutamate receptor 5 (mGluR5) in vitro and in the caudate and putamen (CPu). The potential role of this interaction in the regulation of psychomotor behaviour was also evaluated after administration of cocaine. Active JNK phosphorylates a threonine residue at position 1055 in the carboxyl terminus (CT) of mGluR5 in vitro. The binding of active JNK to the D-motif within CT2 is necessary for that phosphorylation. Interaction of phosphorylated JNK and mGluR5 occurs in the CPu. Unilateral interference of the interaction decreases the repeated cocaine-induced increases in locomotor activity and conditioned place preference. These findings suggest that activation of JNK has the capability to interact with mGluR5 in the CPu. Phosphorylation of mGluR5 following the JNK-mGluR5 interaction may be responsible for the potentiation of behavioural sensitisation and cocaine-wanting behaviour in response to cocaine administration.

Roles of non-receptor tyrosine kinases in pathogenesis and treatment of depression.

Major depressive disorder is a chronic psychiatric disease with a high prevalence. Brain mechanisms for depression at cellular and molecular levels are far from clear. Increasing evidence from clinical and preclinical studies reveals critical roles of the non-receptor tyrosine kinase (nRTK) superfamily in the pathophysiology, symptomatology, and therapy of depression. To date, several nRTK members from three nRTK subfamilies, i.e., the Src family kinase (SFK), the Janus tyrosine kinase (JAK) and the focal adhesion kinase (FAK) subfamilies, may connect to the intracellular, intranuclear, and synaptic signaling network linking chronic stress to depression- and anxiety-like behavior. These SFK/JAK/FAK nRTKs are abundantly expressed in the prefrontal cortex and hippocampus, two core limbic regions implicated in depression, and are enriched at synaptic sites. In various acute or chronic animal models of depression, the nRTKs were significantly altered (up- or downregulated) in their phosphorylation, expression, subcellular/subsynaptic distribution, and/or function. Stress that precipitates depressive behavior also influenced the interaction of nRTKs with other signaling molecules and downstream substrates, including ionotropic and metabotropic glutamate receptors. The commonly-used antidepressants showed the ability to alter nRTK activity. In sum, the limbic SFK/JAK/FAK nRTKs are sensitive to stress and undergo drastic adaptations in response to chronic depression. These long-lasting adaptations contribute to the remodeling of signaling network or synaptic plasticity critical for the vulnerability to depression and the therapeutic efficacy of antidepressants.

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.

Placental-Cadherin, a biomarker for local immune status and poor prognosis among patients with tongue squamous cell carcinoma.

BACKGROUND: The prognostic and clinicopathological value of placental-Cadherin (CDH3) in multiple cancers is controversial. The diagnostic significance and functional mechanism of CDH3 in tongue squamous cell carcinoma (TSCC) have not been thoroughly investigated. This study aims to clarify the potential of CDH3 as biomarker for TSCC. METHODS: Here, meta-analysis, bioinformatics, along wet-lab techniques were employed to evaluate the diagnostic, as well as the prognostic value of CDH3 in diverse types of cancers, especially TSCC. Meta-analysis was used to determine the influence of CDH3 on prognostic and clinicopathological features in numerous cancers. Molecular biology function was used to investigate the role of CDH3 in TSCC cells. The relationship of CDH3 with tumor-infiltrating immune cells (TIICs) in TSCC was assessed using CIBERSORT. Moreover, gene set enrichment analysis (GSEA) was done based on TCGA. Besides, the hub genes and associated cascades were uncovered based on gene co-expression with CDH3. RESULTS: CDH3 upregulation correlated with worse overall survival and disease-free survival in various cancers. CDH3 was validated as an independent risk factor for HNSC and was linked to the onset of tumors, tumor stage, and infiltration depth. CDH3 silencing inhibited cell growth and induced apoptosis of the CAL-27 cell line. CDH3 expression level correlated with infiltration by macrophages, T cells, T cell regulatory cells (Tregs), and plasma cells in TSCC. GSEA revealed that CDH3 influences multiple cancer-associated cascades. Besides, CBX3, CCHCR1, along NFYC were identified as the core hub genes for CDH3. CONCLUSION: We identified CDH3 as a pan-cancer gene with potential prognostic and diagnostic significance in various cancers, particularly in TSCC, where it is tumorigenic.

Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update.

Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are G protein-coupled receptors and are broadly expressed in the mammalian brain. These receptors play key roles in the modulation of normal glutamatergic transmission and synaptic plasticity, and abnormal mGlu1/5 signaling is linked to the pathogenesis and symptomatology of various mental and neurological disorders. Group I mGlu receptors are noticeably regulated via a mechanism involving dynamic protein-protein interactions. Several synaptic protein kinases were recently found to directly bind to the intracellular domains of mGlu1/5 receptors and phosphorylate the receptors at distinct amino acid residues. A variety of scaffolding and adaptor proteins also interact with mGlu1/5. Constitutive or activity-dependent interactions between mGlu1/5 and their interacting partners modulate trafficking, anchoring, and expression of the receptors. The mGlu1/5-associated proteins also finetune the efficacy of mGlu1/5 postreceptor signaling and mGlu1/5-mediated synaptic plasticity. This review analyzes the data from recent studies and provides an update on the biochemical and physiological properties of a set of proteins or molecules that interact with and thus regulate mGlu1/5 receptors.

Is There Any Evidence of Premature, Accentuated and Accelerated Aging Effects on Neurocognition in People Living with HIV? A Systematic Review.

Despite evidence of premature, accentuated and accelerated aging for some age-related conditions such as cardiovascular diseases in people living with HIV (PLHIV), the evidence for these abnormal patterns of aging on neurocognition remains unclear. Further, no systematic review has been dedicated to this issue. Using PRISMA guidelines, we searched standard databases (PubMed, EMBASE, CINAHL and PsycINFO). Articles were included if they analyzed and reported the effect of age on neurocognition among PLHIV as one of their major findings, if they were conducted in the combination anti-retroviral therapy era (after 1996) and published in a peer-reviewed journal in English. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) appraisal tools. To systematically target the abnormal patterns of neurocognitive aging, we define premature cognitive aging as significant interaction effect of HIV status and age on cross-sectional neurocognitive test performance covering both the normal and abnormal performance range; accentuated cognitive aging as significant interaction effect of HIV status and age on cross-sectional neurocognitive impairment (NCI) rate, thus covering the abnormal performance range only; accelerated cognitive aging as significant interaction effect of HIV status and age on longitudinal neurocognitive test performance or incidence of NCI. Because these definitions require an age-comparable HIV-negative (HIV-) control group, when no controls were included, we determined the range of the age effect on neurocognitive test performance or NCI among PLHIV. A total of 37 studies originating from the US (26), UK (2), Italy (2), Poland (2), China (2), Japan (1), Australia (1), and Brazil (1) were included. Six studies were longitudinal and 14 included HIV- controls. The quality appraisal showed that 12/37 studies neither used an age-matched HIV- controls nor used demographically corrected cognitive scores. A meta-analysis was not possible because study methods and choice of neurocognitive measurement methods and outcomes were heterogeneous imposing a narrative synthesis. In studies with an HIV- control sample, premature neurocognitive aging was found in 45% of the cross-sectional analyses (9/20), while accelerated neurocognitive aging was found in 75% of the longitudinal analyses (3/4). There was no evidence for accentuated aging, but this was tested only in two studies. In studies without an HIV- control sample, the age effect was always present but wide (NCI OR = 1.18-4.8). While large sample size (> 500) was associated with abnormal patterns of cognitive aging, most of the studies were under powered. Other study characteristics such as longitudinal study design and higher proportion of older participants were also associated with the findings of abnormal cognitive aging. There is some support for premature and accelerated cognitive aging among PLHIV in the existing literature especially among large and longitudinal studies and those with higher proportion of older samples. Future HIV and cognitive aging studies need to harmonize neuropsychological measurement methods and outcomes and use a large sample from collaborative multi-sites to generate more robust evidences.

STI testing among young people attending music festivals in New South Wales, Australia: exploring the client segmentation concept in the 'Down to Test' program.

Background The 'Down to Test (DTT)' campaign is a sexually transmissible infection (STI) social marketing intervention delivered through outdoor music festival activations and supported by digital media communications in New South Wales, Australia. This paper investigates whether and how the tailored messages reached the intended audience. Methods Data was collected through three annual rounds of online surveys post campaign exposure, targeting young people (aged 15-29years) attending 14 music festivals in NSW from October 2017 to March 2020. Descriptive statistics, principal component analysis and multivariable logic regression were applied to identify the key client segment and factors associated with a strong intention for future STI screening. Results Of the 10044 participants with a valid urine specimen submitted, 261 (2.8%) tested positive for chlamydia. Altogether, 1776 participants (median age=22) self-completed the evaluation surveys online with more being female (73.4%) than male (26.2%). Participants were mostly Australian-born (89.5%), heterosexual (82.6%) and the majority being sexually active (96.7%). Rates of self-reported lifetime STI testing (70.4%) and intention for future STI screening ('definitely yes' in the next 12months, 39.0%) were also high. The most significant factor associated with future intention for STI testing is the Sexual Experience and Perception Factor (adjusted odds ratio [AOR]=2.02; 95%CI 1.76-2.32; P<0.001), followed by the Sexual Beliefs and Attitudes Factor (AOR=1.14; 95% CI 1.01-1.30; P<0.05). Conclusions The NSW state-wide DTT campaign has largely reached sexually active youth who are attentive to sexual health promotion messages and contributed to enhanced STI screening in a fun and peer-supportive environment.

Using Videoconferencing Focus Groups in Sexual and Reproductive Health Research With Chinese Im/Migrants in Australia.

Videoconferencing focus groups have emerged as a popular method for collecting qualitative data. However, its use in sexual and reproductive health research is still very much in its infancy. Based on participants' feedback and researchers' reflections on using videoconferencing focus groups to collect sexual and reproductive health data with 39 heterosexual and non-heterosexual Chinese im/migrants in Australia, we discuss some of the key lessons learned, and considerations involved in shifting from face-to-face to online focus groups. Overall, videoconferencing focus groups appeared to be a highly feasible and acceptable way to discuss "sensitive" topics with Chinese im/migrants. Importantly, researchers need to be both creative and reflexive during the research process and must not forget that the success of a study lies not only in troubleshooting technical issues but also in cultivating and maintaining a trusting relationship with research participants.

Estimation of the impact of changing drug-use trend on HIV, hepatitis C and syphilis epidemics among people who use synthetic drug-only, polydrug and heroin-only during 2005-2035 in China: modelling study.

OBJECTIVE: The rapid expansion of the recreational drug market becomes a global health concern. It is worrying that the bacterial and viral infection epidemics linking to drug use may worsen accordingly. This study aimed to estimate the impacts of changing trend and behaviours of using heroin only, synthetic drug (SD) only and polydrug (using SD and heroin concurrently) on HIV, hepatitis C virus (HCV) and syphilis epidemics among people who use drugs in China by 2035. METHODS: We constructed a compartmental model to estimate HIV, HCV and syphilis epidemics in the dynamic drug-use trend by three scenarios: SD-only use, heroin-only use and polydrug use based on Monte Carlo simulations. The parameters for the model were collected from a comprehensive literature search. RESULTS: Our model estimated that polydrug use led to the highest HIV and HCV prevalence among three drug-use patterns. The prevalences were projected to increase from 10.9% (95% CI 10.2% to 11.5%) and 61.7% (95% CI 59.4% to 62.5%) in 2005 to 19.0% (95% CI 17.3% to 20.7%) and 69.1% (95% CI 67.3% to 69.5%), respectively, in 2035 among people using polydrug. Similarly, HIV and HCV prevalence in the SD-only group were projected to increase from 0.4% (95% CI 0.3% to 0.4%) and 19.5% (95% CI 19.4% to 21.7%) to 1.8% (95% CI 1.4 to 2.1%) and 33.7% (95% CI 33.2% to 34.9%) in 2005-2035. Conversely, HIV prevalence in the heroin-only group was projected to decrease from 8.0% (95% CI 7.6% to 8.1%) to 2.2% (95% CI 2.0% to 2.3%) in 2005-2035. Syphilis prevalence was estimated to remain unchanged in all population groups within this time frame. It was projected that the proportion of HIV transmitted by sexual transmission will increase compared with unsafe injection transmission in all people who use drugs from 2005 to 2035. CONCLUSION: Our modelling suggests that polydrug use is projected to lead to the highest HIV and HCV disease burden by 2035, and the proportion of HIV transmitted by sexual transmission will increase. Current HIV intervention among people using heroin seems effective according to our estimation.