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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 p

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).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.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.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.

OBJECTIVES To assess trends in HIV prevention strategies among Australian gay and bisexual men (GBM) since the introduction of preexposure prophylaxis (PrEP), the level of net prevention coverage (the use of safe strategies), and the characteristics of HIV-negative and untested GBM who remain at risk of HIV. DESIGN Repeated behavioural surveillance of GBM recruited from venues, events and online in seven Australian states and territories. METHODS Participants with casual male partners were included. Trends in sexual practices, prevention strategies, net prevention coverage and the characteristics of 'at risk' participants were assessed with binary and multivariate logistic regression. RESULTS A total of 32 048 survey responses (2014-2019) were included. The proportion of participants who reported consistent condom use declined (44.6-23.2%). The proportion who reported any condomless anal intercourse with casual partners increased (37.4-62.0%) but net prevention coverage also increased (68.1-74.9%), with higher levels of undetectable viral load among HIV-positive participants and rapidly increasing PrEP use by HIV-negative participants. PrEP became the most commonly reported prevention strategy in 2019 (31.1%). The analysis of 'at risk' participants showed that they became more likely to report frequent condomless anal intercourse with casual partners but had fewer partners and more partners with undetectable viral load or on PrEP. 'At risk' participants became more likely to identify as bisexual and to be born overseas. CONCLUSION There has been a rapid, historic shift in HIV prevention among GBM in Australia. Net prevention coverage has increased among GBM and 'at risk' GBM have become less at risk of HIV, facilitating reductions in HIV transmission.

Objectives Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over‐representation of non‐community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non‐HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV‐negative controls. Methods This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA

ObjectiveThe 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.MethodsWe 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.ResultsOur 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.ConclusionOur 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.

Increasing HIV testing frequency in gay and bisexual men (GBM) is critical to reducing the time between HIV infection and diagnosis. Using anonymous national behavioural surveillance data (2013–2018) from 43,753 surveys of Australian GBM, we examined HIV testing frequency trends and factors differentiating PrEP-users, non-PrEP-users reporting two or more tests in the previous year, and non-PrEP-users reporting less frequent testing. The proportion tested at least annually increased from 64.4% in 2013 to 70.8% in 2018 (p-trend

In Australia, HIV testing services have become increasingly available in non-traditional settings such as peer-led, community-based services to expand access and increase uptake of HIV testing among gay and bisexual men (GBM). This study aimed to compare the socio-demographic and behavioural characteristics of GBM whose last HIV test was conducted at a community-based service to GBM whose last test was at a traditional clinical setting. We analysed behavioural surveillance data collected from 5988 participants in seven states and territories in the period 2016-2017. We found that non-HIV-positive GBM who attended community-based services were largely similar to men attending clinic-based settings, particularly in terms of sexual practice and risk of HIV. However, non-HIV-positive GBM who were younger, born in Asia, more socially engaged with other gay men but who had not recently used PrEP were more likely to attend community-based services for their last HIV test. This study points to the successful establishment of community-based HIV testing services in Australia as a way to attract subgroups of GBM at potentially higher risk of HIV.

The medial prefrontal cortex (mPFC) is implicated in the rewarding effect of psychostimulants, although molecular mechanisms underlying the rewarding properties of stimulants in this region are poorly understood. Group I metabotropic glutamate (mGlu) receptors (mGlu1/5 subtypes) are believed to be critical in this event. We thus in this study investigated changes in mGlu1/5 receptor expression and function in the rat mPFC in response to conditioned place preference (CPP) induced by amphetamine. Repeated amphetamine administration (2.5 mg/kg, once daily on alternate days for 10 days) induced reliable CPP. In the mPFC, surface expression of mGlu5 receptors was elevated in rats after amphetamine conditioning. mGlu5 receptors were also increased at synaptic and extrasynaptic sites in amphetamine-conditioned rats. Expression of mGlu1 receptors was stable in surface and synaptic compartments, while it was elevated in the extrasynaptic location. In mPFC neurons, the mGlu1/5 agonist-stimulated phosphoinositide signaling pathway was upregulated in its efficacy following amphetamine conditioning. The mGlu1/5 agonist-stimulated Src kinase phosphorylation was also augmented in rats treated with amphetamine. These results demonstrate the sensitivity of mPFC mGlu1/5 receptors to amphetamine-induced CPP. Amphetamine conditioning results in the upregulation of mGlu1/5 receptor expression at subcellular and/or subsynaptic levels and mGlu1/5-mediated postreceptor signaling in mPFC neurons.

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 15–29 years) 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 10 044 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 12 months, 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

Obesity is an increasingly severe global health problem, leading to chronic inflammation and metabolic disorders in both peripheral tissues and the central nervous system. Matcha is a powdered green tea, and it is very popular in recent years as a beverage and food additive. Matcha green tea has been reported to have outstanding potential in regulating obesity-related metabolic syndrome. However, there are few studies on the regulation mechanism of matcha green tea on the central nervous system. In this study, we established a high-fat diet-induced obese mouse model. The results showed that dietary supplementation with matcha could effectively inhibit the weight gain, fat accumulation, glycemia and lipidemia increase, and excessive activation of microglia in the arcuate nucleus of the hypothalamus. Furthermore, we used different concentrations (100%, 80%, 60%, 40%, and 20%, v/v) of ethanol solution to prepare matcha ethanol extracts, and investigated their effects on palmitic acid-induced inflammation of microglial BV-2 cells. The results showed that matcha ethanol extracts could significantly reduce the release of inflammatory cytokines and the expression and phosphorylation of JAK2 and STAT3.

Recent increases in the availability of pre-exposure prophylaxis (PrEP) internationally have widened the range of HIV prevention strategies available to gay and bisexual men. This paper aimed to quantify the use of different risk reduction strategies and compare characteristics of men who rarely use any strategies with those who regularly use condoms or PrEP. Using national cross-sectional data from the Gay Community Periodic Surveys in Australia, comparisons were made between regular condom users (37.1% of participants), PrEP users (50.1%), and men who infrequently used any risk reduction strategies (12.8%). The proportion of gay and bisexual men reporting infrequent use of HIV risk reduction strategies has decreased in recent years. These men reported less frequent high-risk sexual practices than PrEP users and also reported less recent HIV testing than either PrEP or condom users. Men who infrequently use HIV risk reduction strategies should be encouraged to test for HIV more regularly and to utilise prevention strategies that align with their infrequent high-risk behaviour.

The metabotropic glutamate (mGlu) receptor 5 is a G protein-coupled receptor and is densely expressed in the mammalian brain. Like other glutamate receptors, mGlu5 receptors are tightly regulated by posttranslational modifications such as phosphorylation, although underlying mechanisms are incompletely investigated. In this study, we investigated the role of a prime kinase, extracellular signal-regulated kinase 1 (ERK1), in the phosphorylation and regulation of mGlu5 receptors in vitro and in striatal neurons. We found that recombinant ERK1 proteins directly bound to the C-terminal (CT) tail of mGlu5 receptors in vitro. Endogenous ERK1 also interacted with mGlu5 receptor proteins in adult rat striatal neurons in vivo. The kinase showed the ability to phosphorylate mGlu5 receptors. A serine residue in the distal region of mGlu5 CT was found to be a primary phosphorylation site sensitive to ERK1. In functional studies, we found that pharmacological inhibition of ERK with an inhibitor U0126 reduced the efficacy of mGlu5 receptors in stimulating production of cytoplasmic inositol-1,4,5-triphosphate, a major downstream conventional signaling event, in striatal neurons under normal conditions. These results identify mGlu5 as a new biochemical substrate of ERK1. The kinase can interact with and phosphorylate an intracellular domain of mGlu5 receptors in striatal neurons and thereby control its signaling efficacy.

The mitogen-activated protein kinase (MAPK), especially its extracellular signal-regulated kinase (ERK) subfamily, is a group of kinases enriched in the mammalian brain. While ERK is central to cell signaling and neural activities, the regulation of ERK by transmitters is poorly understood. In this study, the role of acetylcholine in the regulation of ERK was investigated in adult rat striatum in vivo. We focused on muscarinic M1 and M4 receptors, two principal muscarinic acetylcholine (mACh) receptor subtypes in the striatum. A systemic injection of the M1-preferring antagonist telenzepine did not alter ERK phosphorylation in the two subdivisions of the striatum, the caudate putamen and nucleus accumbens. Similarly, telenzepine did not affect ERK phosphorylation in the medial prefrontal cortex (mPFC), hippocampus, and cerebellum. Moreover, telenzepine had no effect on the ERK phosphorylation induced by dopamine stimulation with the psychostimulant amphetamine. In contrast to telenzepine, the M4-preferring antagonist tropicamide consistently increased ERK phosphorylation in the striatum and mPFC. This increase was rapid and transient. Tropicamide and amphetamine when coadministered at subthreshold doses induced a significant increase in ERK phosphorylation. These results demonstrate that mACh receptors exert a subtype-specific modulation of ERK in striatal and mPFC neurons. While the M1 receptor antagonist had no effect on ERK phosphorylation, M4 receptors inhibit constitutive and dopamine-stimulated ERK phosphorylation in these dopamine-innervated brain regions.

Major depressive disorder is a common form of mental illness. Many brain regions are implicated in the pathophysiology and symptomatology of depression. Among key brain areas is the striatum that controls reward and mood and is involved in the development of core depression-like behavior in animal models of depression. While molecular mechanisms in this region underlying depression-related behavior are poorly understood, the glutamatergic input to the striatum is believed to play a role. In this study, we investigated changes in metabotropic glutamate (mGlu) receptor expression and signaling in the striatum of adult rats in response to prolonged (10-12 weeks) social isolation, a pre-validated animal paradigm modeling depression in adulthood. We found that mGlu5 receptor protein levels in the striatum were increased in rats that showed typical depression- and anxiety-like behavior after chronic social isolation. This increase in mGlu5 receptor expression was seen in both subdivisions of the striatum, the nucleus accumbens and caudate putamen. At subcellular and subsynaptic levels, mGlu5 receptor expression was elevated in surface membranes at synaptic sites. In striatal neurons, the mGlu5-associated phosphoinositide signaling pathway was augmented in its efficacy after prolonged social isolation. These data indicate that the mGlu5 receptor is a sensitive substrate of depression. Adulthood social isolation leads to the up-regulation of mGlu5 receptor expression and function in striatal neurons.

Background The exponential growth in the reach and development of new technologies over the past decade means that mobile technologies and social media play an increasingly important role in service delivery models to maximise HIV testing and access to treatment and care. This systematic review examines the impact of electronic and mobile technologies in medical care (eHealth) in the linkage to and retention of priority populations in the HIV treatment and care cascade, focussing on the Asia-Pacific region. Methods The review was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the Cochrane Collaboration guidelines. Both grey and published scientific literature from five different databases were searched for all original articles in English published from 2010 to 2017. Studies conducted outside the Asia-Pacific region or not including HIV priority populations were excluded. The methodological quality of studies included in the review was assessed using the Quality Assessment Tool for Quantitative Studies. Results The database search identified 7309 records. Of the 224 peer-reviewed articles identified for full text review, 16 studies from seven countries met inclusion criteria. Six cross sectional studies found evidence to support the use of eHealth, via text messages, instant messaging, social media and health promotion websites, to increase rates of HIV testing and re-testing among men who have sex with men (MSM). Evidence regarding the efficacy of eHealth interventions to improve antiretroviral treatment (ART) adherence was mixed, where one randomised controlled trial (RCT) showed significant benefit of weekly phone call reminders on improving ART adherence. Three further RCTs found that biofeedback eHealth interventions that provided estimated ART plasma concentration levels, showed promising results for ART adherence. Conclusions This review found encouraging evidence about how eHealth can be used across the HIV treatment and care cascade in the Asia-Pacific region, including increasing HIV testing and re-testing in priority populations as well as ART adherence. eHealth interventions have an important role to play in the movement towards the end of AIDS, particularly to target harder-to-reach HIV priority populations, such as MSM. Electronic supplementary material The online version of this article (10.1186/s12879-018-2972-5) contains supplementary material, which is available to authorized users.

Two key transmitters in the medial prefrontal cortex (mPFC), dopamine and acetylcholine, are believed to interact with each other to modulate local glutamatergic transmission, although molecular mechanisms underlying their crosstalk are poorly understood. Here we investigated effects of pharmacological manipulations of dopamine and muscarinic receptors on phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult rat mPFC in vivo. We found that an agonist selective for Gαs-coupled dopamine D1 receptors, SKF81297, increased AMPA receptor GluA1 subunit phosphorylation at a protein kinase A-sensitive site (S845), while SKF81297 had no effect on GluA1 phosphorylation at S831. An agonist for Gαi/o-coupled dopamine D2 receptors, quinpirole, also increased S845 but not S831 phosphorylation. When coinjected, the two agonists induced an additive increase in S845 phosphorylation. The D1 receptor antagonist SCH23390 blocked the SKF81297/quinpirole-stimulated S845 phosphorylation. The D2 antagonist eticlopride also partially blocked S845 responses to SKF81297/quinpirole. VU0152100, a positive allosteric modulator selective for Gαi/o-coupled muscarinic M4 receptors, reduced the S845 phosphorylation induced by SKF81297 and quinpirole injected alone or together. In contrast, coinjection of subthreshold doses of tropicamide, an M4 antagonist, and SKF81297 facilitated S845 phosphorylation. Additionally, coadministered SFK81297 and quinpirole increased the abundance of mPFC GluA1 at extrasynaptic sites. These data reveal that both D1 and D2 receptors upregulate GluA1 phosphorylation in mPFC neurons probably via a direct and indirect mechanism, respectively. The indirect mechanism involves M4 receptors which generally counteract the effect of dopamine on GluA1 phosphorylation.

SMS reminders sent to personal mobiles are increasingly used by clinical services to promote patient engagement, including adherence to antiretroviral treatment (ART) for HIV. From August to September 2015, a 6-week, randomised SMS reminder for ART adherence intervention was implemented among 98 HIV-positive clients of Australian's largest HIV charitable organisation located in Sydney. This was followed by a mixed-method evaluation, comprising a self-completed online survey and a one-to-one interview. Of the 62 survey participants, all being men, the majority were gay (85.5%) and living long-term with HIV (median year of HIV diagnosis = 1998). While everyone was on ART, a substantial proportion (n = 27, 43.5%) had interrupted treatment in the past. At the end of the intervention, based on the standard SMAQ measure, 82% had consistently adhered to ART in the previous week. While there was no statistically significant intervention effect, perceiving less stigma were independently associated with better ART adherence (adjusted odds ratio = 0.37; 95% CI 0.16-0.89; P = .026). Of the 11 interviewees, despite limited add-on effects on individual ART adherence, the campaign was well-received as a unique community support service. This study underscores the essential role of empowerment through enhancing disease self-management, increasing social support and reducing stigma, particularly for long-term HIV survivors. SMS messaging, part of mHealth, delivered by community services could have broader impacts on reducing health and social inequity.

Co-infection with hepatitis B (HBV) and C (HCV) is common among people living with HIV (PLHIV). This study investigates the impacts of hepatitis co-infection on antiretroviral therapy (ART) outcomes and hepatotoxicity in PLHIV. The cohort study included 1984 PLHIV. Hepatotoxicity was defined by elevated alanine aminotransferase (ALT) levels. ART outcomes were measured by CD4 cell counts, viral load, and mortality rate in patients. Among 1984 PLHIV, 184 (9.3%) were co-infected with HBV and 198 (10.0%) with HCV and 54 (2.7%) were co-infected with HBV and HCV. Of these patients, 156 (7.9%) had ALT elevation ≥ grade 1 at baseline. During the course of ART, the mortality rate and its adjusted hazard ratio (AHR) in PLHIV who were co-infected with HCV (2.6/100 person-years [py], AHR = 2.3, 95%CI 1.1-4.7) was higher than for patients with mono-infected HIV, as it was for those with an elevated ALT (4.4/100 py, AHR = 3.8, [1.7-8.2]) at baseline compared to those with normal ALT. After 6-12 months of ART, the incidence of hepatotoxicity among all the patients was 3.7/100 py. The risk of hepatotoxicity was higher in HCV co-infected (18.6/100 py, adjusted odds ratio [AOR] = 12.4, [8.1-18.2]) than HIV mono-infected patients, and for all regimens (nevirapine: 30.0/100 py, 34.2, 7.3-47.9; zidovudine/stavudine: 24.7/100 py, 22.1, 7.1-25.5; efavirenz: 14.5/100 py, 9.4, 3.5-19.2; lopinavir/ritonavir: 40.1/100 py, 52.2, 9.5-88.2) except tenofovir (4.3/100 py, 4.9, 0.8-9.5). Patients with HBV/HCV co-infected had high hepatotoxicity (10.0/100 py, 6.3, 1.2-23.3) over the same period. Patients with HCV co-infection and HBV/HCV co-infection demonstrated higher hepatotoxicity rate compared with HIV mono-infected patients in China.

Background The success of ‘treatment as prevention’ (TasP) to control HIV relies on the uptake of testing across priority population groups. Innovative strategies including; rapid HIV testing (RHT) in community and outreach settings, engaging peer service providers, and not requiring disclosure of sexual history have been designed to increase access. This paper reports on the implementation of ‘RAPID’, a community-based testing program in Queensland, Australia that employs these strategies to increase access to testing. Methods Service data, including client registration forms and a satisfaction survey from all clients attending RAPID between August 2014 and July 2015 were analysed. Results In 2014/2015 1,199 people attended RAPID to receive a free HIV test. The majority were urban-based gay men. 17.1% were first-time testers and 20.1% of participants were not eligible to access Medicare, Australia’s universal health care scheme. Conclusions RAPID’s evidence-based strategies appear to facilitate access to HIV testing, particularly among those who have never tested before; however the implications for the ongoing treatment and care of people ineligible for Medicare, who test positive to HIV warrants careful consideration. Electronic supplementary material The online version of this article (doi:10.1186/s12913-017-2249-5) contains supplementary material, which is available to authorized users.

The landscape of HIV testing has changed significantly in recent years following the rise in importance of the 'treatment as prevention' strategy and advancements in new HIV testing and prevention technologies. This review provides a synthesis of qualitative research findings published since 2010 on preferences and practices of men who have sex with men (MSM) surrounding HIV testing in high-income settings. MSM are one of the hardest groups to reach with standard or conventional HIV testing approaches. To develop innovative testing strategies for this particular group, a good understanding of their concerns, barriers and facilitators of accessing HIV testing is needed. This updated review provides valuable information for improving existing programs and designing new testing services for MSM.

Several Src family kinase (SFK) members are expressed in the mammalian brain and serve as key kinases in the regulation of a variety of cellular and synaptic events. These SFKs may be subject to the modulation by dopamine, although this topic has been investigated incompletely. In this study, we explored whether dopamine D2 receptors (D2Rs) regulate SFKs in adult rat brains in vivo. We investigated the role of D2Rs in two forebrain areas, the medial prefrontal cortex (mPFC) and hippocampus, since dopamine plays a pivotal role in regulating activity of mPFC and hippocampal neurons and D2Rs are expressed in these regions. We found that a systemic injection of a D2R selective antagonist eticlopride elevated phosphorylation of SFKs at a conserved autophosphorylation site, an event correlated with activation of SFKs, in the mPFC. Similarly, antagonism of D2Rs by haloperidol increased SFK phosphorylation. In contrast, eticlopride and haloperidol did not alter SFK phosphorylation in the hippocampus. The effect of eticlopride was time-dependent and relatively delayed. Among two common SFK members enriched at synaptic sites, eticlopride selectively altered phosphorylation of Fyn but not Src. Our data suggest that D2Rs exert an inhibitory effect on the activity-related phosphorylation of Fyn in the mPFC under normal conditions.

Data from repeated, national behavioural HIV surveillance was used to identify similarities and differences between young gay and bisexual men (YGBM) aged 16–24 (n = 1608) and older GBM aged 25–49 (n = 6266), in order to quantify risks and identify gaps in HIV prevention. Trend analyses from 2014 to 2018 are also reported. While there were similar rates of condomless anal intercourse with casual partners in both age groups, YGBM had lower rates of HIV testing and PrEP use but also fewer male partners. Our results suggest most YGBM have lower HIV risk than older GBM but a minority merit enhanced testing and prevention efforts.

Objective The adenosine A1 receptor is a Gαi/o protein‐coupled receptor and inhibits upon activation cAMP formation and protein kinase A (PKA) activity. As a widely expressed receptor in the mammalian brain, A1 receptors are implicated in the modulation of a variety of neuronal and synaptic activities. In this study, we investigated the role of A1 receptors in the regulation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in the adult rat brain in vivo. Methods Adult male Wistar rats were used in this study. After a systemic injection of the A1 antagonist DPCPX, rats were sacrificed and several forebrain regions were collected for assessing changes in phosphorylation of AMPA receptors using Western blots. Results A systemic injection of the A1 antagonist DPCPX induced an increase in phosphorylation of AMPA receptor GluA1 subunits at a PKA‐dependent site, serine 845 (S845), in the two subdivisions of the striatum, the caudate putamen, and nucleus accumbens. DPCPX also increased S845 phosphorylation in the medial prefrontal cortex (mPFC) and hippocampus. The DPCPX‐stimulated S845 phosphorylation was a transient and reversible event. Blockade of Gαs/olf‐coupled dopamine D1 receptors with a D1 antagonist SCH23390 abolished the responses of S845 phosphorylation to DPCPX in the striatum, mPFC, and hippocampus. DPCPX had no significant impact on phosphorylation of GluA1 at serine 831 and on expression of total GluA1 proteins in all forebrain regions surveyed. Conclusion These data demonstrate that adenosine A1 receptors maintain an inhibitory tone on GluA1 S845 phosphorylation under normal conditions. Blocking this inhibitory tone leads to the upregulation of GluA1 S845 phosphorylation in the striatum, mPFC, and hippocampus via a D1‐dependent manner., Our data demonstrate that adenosine A1 receptors maintain an inhibitory tone on GluA1 S845 phosphorylation under normal conditions. Blocking this inhibitory tone leads to the upregulation of GluA1 S845 phosphorylation in the striatum, mPFC, and hippocampus via a D1‐dependent manner.

Using repeated, cross-sectional behavioural surveillance data from Australia, we assessed trends in relationship agreements and casual sex among HIV-negative and untested gay and bisexual men who had regular partners during 2013–2018. We conducted three analyses: (i) trends in relationship agreements and casual sex over time; (ii) bivariate comparisons of PrEP users and non-PrEP-users to identify factors associated with PrEP use; and (iii) multivariate logistic regression to identify factors independently associated with PrEP use. The analysis of trends over time included 21,593 men, from which a sub-sample (n = 3764) was used to compare PrEP users and non-PrEP-users. We found a large increase in agreements that allowed condomless sex with casual partners, particularly by PrEP users in relationships (nearly 40% of whom had such an agreement). A further 34% of PrEP users reported having casual condomless sex without an agreement that permitted that behaviour, while 13% of non-PrEP-users also reported condomless sex with casual partners without an agreement. PrEP use was independently associated with having agreements permitting condomless sex with casual partners, recent condomless sex with casual partners, having greater numbers of male partners, recent post-exposure prophylaxis use, having an HIV-positive regular male partner, and recent condomless sex with regular male partners. Our findings show a shift away from relationship agreements in which condomless sex was only sanctioned between regular partners.

Background A substantial minority of patients living with HIV refuse or cease antiretroviral therapy (ART), have virological failure (VF) or develop an AIDS-defining condition (ADC) or serious non-AIDS event (SNAE). It is not understood which socioeconomic and psychosocial factors may be associated with these poor outcomes. Methods: Thirty-nine patients with poor HIV treatment outcomes, defined as those who refused or ceased ART, had VF or were hospitalised with an ADC or SNAE (cases), were compared with 120 controls on suppressive ART. A self-report survey recorded demographics, physical health, life stressors, social supports, HIV disclosure, stigma or discrimination, health care access, treatment adherence, side effects, health and treatment perceptions and financial and employment status. Socioeconomic and psychosocial covariates significant in bivariate analyses were assessed with conditional multivariable logistic regression, adjusted for year of HIV diagnosis. Results: Cases and controls did not differ significantly with regard to sex (96.2% (n = 153) male) or age (mean (± s.d.) 51 ± 11 years). Twenty cases (51%) had refused or ceased ART, 35 (90%) had an HIV viral load >50 copies mL–1, 12 (31%) were hospitalised with an ADC and five (13%) were hospitalised with a new SNAE. Three covariates were independently associated with poor outcomes: foregoing necessities for financial reasons (adjusted odds ratio (aOR) 3.1, 95% confidence interval (95% CI) 1.3–7.6, P = 0.014), cost barriers to accessing HIV care (aOR 3.1, 95% CI 1.0–9.6, P = 0.049) and lower quality of life (aOR 3.8, 95% CI 1.5–9.7, P = 0.004). Conclusions: Despite universal health care, socioeconomic and psychosocial factors are associated with poor HIV outcomes in adults in Australia. These factors should be addressed through targeted interventions to improve long-term successful treatment.

Acetylcholine (ACh) is a key transmitter in the mesocorticolimbic circuit. By interacting with muscarinic ACh receptors (mAChR) enriched in the circuit, ACh actively regulates various neuronal and synaptic activities. The extracellular signal-regulated kinase (ERK) is one of members of the mitogen-activated protein kinase family and is subject to the regulation by dopamine receptors, although the regulation of ERKs by limbic mAChRs is poorly understood. In this study, we investigated the role of mAChRs in the regulation of ERK phosphorylation (activation) in the mesocorticolimbic system of adult rat brains in vivo. We targeted a sub-pool of ERKs at synaptic sites. We found that a systemic injection of the mAChR antagonist scopolamine increased phosphorylation of synaptic ERKs in the striatum (caudate putamen and nucleus accumbens) and medial prefrontal cortex (mPFC). Increases in ERK phosphorylation in both forebrain regions were rapid and transient. Notably, pretreatment with a dopamine D1 receptor (D1R) antagonist SCH23390 blocked the scopolamine-stimulated ERK phosphorylation in these brain regions, while a dopamine D2 receptor antagonist eticlopride did not. Scopolamine and SCH23390 did not change the amount of total ERK proteins. These results demonstrate that mAChRs inhibit synaptic ERK phosphorylation in striatal and mPFC neurons under normal conditions. Blockade of this inhibitory mAChR tone leads to the upregulation of ERK phosphorylation likely through a mechanism involving the level of D1R activity.

BACKGROUND Prevalence of anxiety and mood disorders (AMDs) in HIV-infected individuals has varied widely because of the variety of measurements used and differences in risk factor profiles between different populations. We aimed to examine the relationship between HIV status and hospitalization for AMDs in gay and bisexual men (GBM). DESIGN AND METHODS HIV-infected (n = 557) and HIV-uninfected (n = 1325) GBM recruited in Sydney, Australia were probabilistically linked to their hospital admissions and death notifications (2000-2012). Random-effects Poisson models were used to assess HIV risk factors for hospitalization. Cox regression methods were used to assess risk factors for mortality. RESULTS We observed 300 hospitalizations for AMDs in 15.3% of HIV-infected and 181 in 5.4% of HIV-uninfected participants. Being infected with HIV was associated with a 2.5-fold increase in risk of hospitalization for AMDs in GBM. Other risk factors in the HIV-infected cohort included previous hospitalization for HIV-related dementia, a more recent HIV diagnosis, and a CD4 T-cell count above 350 cells per cubic millimeter. Being hospitalized for an AMD was associated with a 5.5-fold increased risk of mortality; this association did not differ by HIV status. An association between substance use and mortality was observed in individuals hospitalized for AMDs. CONCLUSIONS There is a need to provide more effective strategies to identify and treat AMDs in HIV-infected GBM. This research highlights the importance of further examination of the effects of substance use, neurocognitive decline, and AMDs on the health of HIV-infected individuals.

BACKGROUND: HIV prevention cascades can assist in monitoring the implementation of prevention methods like preexposure prophylaxis (PrEP). We developed 2 PrEP cascades for Australia's primary HIV-affected population, gay and bisexual men. METHODS: Data were drawn from 2 national, repeated, cross-sectional surveys (the Gay Community Periodic Surveys and PrEPARE Project). One cascade had 3 steps, and the other had 7 steps. Trends over time were assessed using logistic regression. For the most recent year, we identified the biggest drop between steps in each cascade and compared the characteristics of men between the 2 steps using multivariate logistic regression. RESULTS: Thirty-nine thousand six hundred and seventy non-HIV-positive men participated in the Periodic Surveys during 2014-2018. PrEP eligibility increased from 28.1% (1901/6762) in 2014 to 37.3% (2935/7878) in 2018 (P

Direct-Acting Antiviral (DAA) treatments for hepatitis C have been widely promoted by health promotion professionals and medical clinicians as being ‘side-effect free’. In this paper, we draw on data that troubles this approach. We used a mixed method design to collect data from people who inject drugs, and who were DAA treatment naive, in New South Wales, Australia. We describe knowledge about and perceptions of DAA treatment. We found that concerns about side effects were commonplace – for example, one-third (37%) of participants who had not taken up treatment worried “a lot” about ‘side effects’ – and that these concerns were underpinned by a general distrust and suspicion of medical institutions and their technologies, including widespread negative associations linked to interferon treatment. In trying to make sense of this, we draw on the concept of counterpublic health and its recognition that the everyday health needs, knowledges and aspirations of subordinated citizens frequently contradict the normative frameworks governing public health interventions. We suggest that failing to engage with concerns about ‘side effects’ could hinder elimination efforts. Our analysis suggests that addressing the issue of ‘side effects’ within the ‘public’ discourse of DAAs will not dampen or damage elimination efforts, as some might fear, but rather it will legitimate the concerns of people who inject, decrease their suspicion of medical interventions, and better support the uptake of DAA treatments.

Obesity is an escalating global epidemic caused by an imbalance between energy intake and expenditure. (&minus, )-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to be conducive to preventing obesity and alleviating obesity-related chronic diseases. However, the role of EGCG in energy metabolism disorders and central nervous system dysfunction induced by a high-fat diet (HFD) remains to be elucidated. The aim of this study was to evaluate the effects of EGCG on brown adipose tissue (BAT) thermogenesis and neuroinflammation in HFD-induced obese C57BL/6J mice. Mice were randomly divided into four groups with different diets: normal chow diet (NCD), normal chow diet supplemented with 1% EGCG (NCD + EGCG), high-fat diet (HFD), and high-fat diet supplemented with 1% EGCG (HFD + EGCG). Investigations based on a four-week experiment were carried out including the BAT activity, energy consumption, mRNA expression of major inflammatory cytokines in the hypothalamus, nuclear factor-kappa B (NF-&kappa, B) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and immunofluorescence staining of microglial marker Iba1 in hypothalamic arcuate nucleus (ARC). Experimental results demonstrated that dietary supplementation of EGCG significantly inhibited HFD-induced obesity by enhancing BAT thermogenesis, and attenuated the hypothalamic inflammation and microglia overactivation by regulating the NF-&kappa, B and STAT3 signaling pathways.

Objective To describe the differences in sexual practices among individuals with various drug administration patterns. Setting A detoxification centre in Southwest China, a part of the Chinese national sentential surveillance network for hepatitis C virus (HCV), HIV and syphilis infections, was recruited. Participants A total of 610 newly enrolled injection drug users (IDUs) from detoxification centre were included during 2015. Primary and secondary outcome measures Self-reported sexual activities, drug-related practices and laboratory-confirmed HCV, HIV and syphilis infection status were collected. Results Of the 610 IDU, 295 (48.4%) used heroin only, 277 (45.4%) poly-drug users reported the mixed use of synthetic drugs (SDs) with heroin and 38 (6.2%) used SDs only. The average daily drug injection frequency for poly-drug users (3.3±1.2 times) was the highest, followed by heroin-only (2.2±0.8 times) and SD-only users (1.2±0.4 time). SD-only drug users reported the highest proportion (86.8%) of engaging in sexual activities in the previous month, with more than half (54.5%) reporting any condomless sex. A higher frequency of daily injecting in heroin-only users was significantly correlated with the less likelihood of sex, condomless sex in the past month, having sex with fixed partners, condomless commercial sex in the previous 12 months (all p0.05). Different patterns of HCV, HIV and syphilis infections prevalence rates were shown among the IDU depending on the roles and length of exposure. Conclusions The daily drug injecting frequency of heroin-only and poly-drug users was negatively associated with sexual activities, but SD-only users kept a high frequent engagement in sex. The interventions for relevant diseases should adapt to characteristics of IDU.

The psychostimulant amphetamine (AMPH) has an impact on a variety of cellular activities in striatal neurons, although underlying signaling mechanisms are incompletely understood. The Src family kinase (SFK) is among key signaling molecules enriched in striatal neurons and is involved in the regulation of a set of discrete downstream targets. Given the likelihood that AMPH may regulate SFKs, we investigated and characterized the effect of AMPH on SFK phosphorylation and enzymatic activity in rat striatal neurons in vivo. We found that AMPH elevated SFK Y416 phosphorylation in striatal slices and the adult rat striatum. This elevation was concentration- and time-dependent and occurred in all subdivisions of the striatum, including the caudate putamen and nucleus accumbens (core and shell). The dopamine D(1) receptor antagonist SCH23390 blocked the effect of AMPH. Between Fyn and Src, AMPH elevated phosphorylation of immunoprecipitated Fyn but not Src and increased Fyn kinase activity in the striatum. In parallel with SFKs, striatal ERK phosphorylation was increased by AMPH. This increase in ERK phosphorylation was reduced by the SFK inhibitor PP2. These results demonstrate that AMPH is able to activate SFKs (mainly Fyn) in striatal neurons via a D(1) receptor-dependent mechanism. Activated SFKs participate in processing the concomitant ERK response to AMPH.

Aims Interest in health-care related trust is growing with the recognition that trust is essential for effective therapeutic encounters. While most trust-related research has been conducted with general patient groups, the experiences of people who inject drugs cannot be understood without acknowledging the critical role social stigma plays in shaping (mis)trust, both generally and in regards to health services specifically. This study examined the experiences of trust among clients and staff of Needle and Syringe Programs (NSPs) in one area of Sydney, Australia. Method In-depth interviews with 12 NSP staff and 31 NSP clients were conducted. Analysis was informed by a five component model of trust, with particular emphasis on the notion of "global trust" as encompassing experiences of stigma and other negative social processes related to injecting drug use. Participant experiences of trust in NSPs were compared with those within other drug-related health services. Particular attention was paid to understanding the relationship between ‘identity' (as a drug user) and ‘legitimacy' (as a service user) and the centrality of this relationship to the experience of global trust for PWID. Results Notions of identity and legitimacy were inextricably bound up with the stigmatisation of drug use, shaping participants' experiences and accounts of trust in NSPs and drug treatment services. Client participants reported high levels of trust in NSPs, especially when compared with drug treatment services, describing being treated like "any other person" even when negotiating ‘sensitive' issues. NSP staff participants described the establishment of trust as not only underpinning their work with clients but as something that required ongoing renewal and demonstration. Conclusion "Global trust" assists us to better understand the complex experiences shaping PWID decisions to engage with and trust health services. The high levels of trust reported between client and NSP need to be recognised as a valuable resource for the delivery of effective health care for people who inject drugs, including encouraging behaviours to support the prevention of blood-borne viruses.

Metabotropic and ionotropic glutamate receptors are closely clustered in postsynaptic membranes and are believed to interact actively with each other to control excitatory synaptic transmission. Metabotropic glutamate receptor 5 (mGluR5), for example, has been well documented to potentiate ionotropic NMDA receptor activity, although underlying mechanisms are poorly understood. In this study, we investigated the role of mGluR5 in regulating trafficking and subcellular distribution of NMDA receptors in adult rat striatal neurons. We found that the mGluR1/5 agonist DHPG concentration-dependently increased NMDA receptor GluN1 and GluN2B subunit expression in the surface membrane. Meanwhile, DHPG reduced GluN1 and GluN2B levels in the intracellular compartment. The effect of DHPG was blocked by an mGluR5 selective antagonist MTEP but not by an mGluR1 selective antagonist 3-MATIDA. Pretreatment with an inhibitor or a specific inhibitory peptide for synapse-enriched Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) also blocked the DHPG-stimulated redistribution of GluN1 and GluN2B. In addition, DHPG enhanced CaMKIIα activity and elevated GluN2B phosphorylation at a CaMKII-sensitive site (serine 1303). These results demonstrate that mGluR5 regulates trafficking of NMDA receptors in striatal neurons. Activation of mGluR5 appears to induce rapid trafficking of GluN1 and GluN2B to surface membranes through a signaling pathway involving CaMKII.

Objectives There is evidence that HIV-positive patients are suffering from a greater burden of morbidity as they age due to nonAIDS-related complications. To date it has been difficult to determine what part of this excess risk is due to the health effects of HIV, its treatment or to lifestyle factors common to gay and bisexual men (GBM). We calculated overall and cause-specific hospitalisation rates and risk factors for hospitalisations in HIV-negative and HIV-positive cohorts of GBM and compare these with rates in the general male population. Methods We conducted a record linkage study, linking two cohorts of HIV-negative (n = 1325) and HIV-positive (n = 557) GBM recruited in Sydney, New South Wales (NSW), Australia with the NSW hospital discharge data register. We compared rates of hospitalisation in the two cohorts and risk factors for hospitalisation using random-effects Poisson regression methods. Hospitalisation rates for each cohort were further compared with those in the general male population using indirect standardisation. Results We observed 2032 hospitalisations in the HIV-negative cohort during 13 016 person-years (PYs) [crude rate: 15.6/100PYs (95% CI: 14.9–16.3)] and 2130 hospitalisations in the HIV-positive cohort during 5571 PYs [crude rate: 38.2/100PYs (95% CI: 36.6–39.9)]. HIV-positive individuals had an increased risk of hospitalisation compared with the HIV-negative individuals [adjusted-IRR: 2.34 (95% CI: 1.91–2.86)] and the general population [SHR: 1.45 (95% CI: 1.33–1.59)]. Hospitalisation rates were lower in the HIV-negative cohort compared with the general population [SHR: 0.72 (95% CI: 0.67–0.78)]. The primary causes of hospitalisation differed between groups. Conclusions HIV-positive GBM continue to experience excess morbidity compared with HIV-negative GBM men and the general population. HIV-negative GBM had lower morbidity compared with the general male population suggesting that GBM identity does not confer excess risk.

Street-based female sex workers (SSWs) are subjected to a relatively high risk of HIV transmission, even higher than establishment-based female sex workers in China. However, very few HIV intervention programmes have targeted this particular group to date. Based in Southwest China, this study aims to identify perceived barriers, demands and suggestions on HIV prevention from the perspectives of SSWs, clients and healthcare providers in Chongqing. Face-to-face, in-depth interviews were conducted in July 2008 with 23 participants. They were recruited by purposive, convenience sampling and included 12 SSWs, 5 male clients, 4 government healthcare providers and 2 outreach workers from a community-based non-governmental organisation. Thematic analysis was used. SSWs were largely rural-to-urban migrants with a low socioeconomic status. Most of their clients shared a similar background. Both SSWs and their clients demonstrated a low awareness of HIV infection and a lack of understanding of effective preventive strategies. Financial hardships, lack of family support, fear of police arrest and stigma in relation to sex work were identified as SSWs' major barriers for accessing healthcare services. Both SSWs and their clients indicated an urgent demand for accessing adequate HIV prevention and care programmes. On the other hand, government organisations trying to provide services to this group have also encountered obstacles, specifically their limited ability to establish mutual trust. Programmes provided by community-based non-governmental organisation, however, were perceived to be more attractive. In conclusion, there remains a substantial gap between the need of adequate HIV prevention services for SSWs and their clients and what is currently available. Strengthening inter-sectoral collaboration, providing specifically tailored health services, actively involving SSW peers and their clients, and reducing stigma in the society are keys to meet this urgent demand by SSWs in China.

Background Blood-borne viruses (BBV) are prevalent among people with opioid dependence but their association with cause-specific mortality has not been examined at the population-level. Methods We formed a population-based cohort of 29,571 opioid substitution therapy (OST) registrants in New South Wales, Australia, 1993–2007. We ascertained notifications of infection and death by record linkage between the Pharmaceutical Drugs of Addiction System (OST data), registers of hepatitis C (HCV), hepatitis B (HBV) and human immunodeficiency virus (HIV) diagnoses, and the National Death Index. We used competing risks regression to quantify associations between notification for BBV infection and causes of death. BBV status, age, year, OST status, and OST episodes were modelled as time-dependent covariates; sex was a fixed covariate. Results OST registrants notified with HCV infection were more likely to die from accidental overdose (subdistribution hazard ratio, 95% Confidence Interval: 1.7, 1.5–2.0), cancer (2.0, 1.3–3.2) and unintentional injury (1.4, 1.0–2.0). HBV notification was associated with a higher hazard of mortality due to unintentional injury (2.1, 1.1–3.9), cancer (2.8, 1.5–5.5), and liver disease (2.1, 1.0–4.3). Liver-related mortality was higher among those notified with HIV only (11, 2.5–50), HCV only (5.9, 3.2–11) and both HIV and HCV (15, 3.2–66). Registrants with an HIV notification had a higher hazard of cardiovascular-related mortality (4.0, 1.6–9.9). Conclusions Among OST registrants, BBVs are a direct cause of death and also a marker of behaviours that can result in unintended death. Ongoing and enhanced BBV prevention strategies and treatment, together with targeted education strategies to reduce risk, are justified.

We investigated the racial or ethnic partner preferences among Australian gay and bisexual men (GBM) as part of a large study of sexual preferences among GBM, to identify whether racial bias was a factor in how GBM expressed their partner preferences. We surveyed 1853 Australian GBM about their partner preferences and preferred sex practices. We used logistic regression to identify whether factors such as age, gay social engagement, or men’s own ethnicity or race were associated with ethnic and racial partner preferences. Mean age was 34.8 years. Ethnic or racial background included: white or “Caucasian” (86.6%), Australian Aboriginal (2.7%), and Asian (6.6%). Mean attraction scores were highest for “Caucasian” men, and lowest for Aboriginal and Asian men. Under half (41.6%) were attracted to all racial or ethnic types; 7.7% were only attracted to “Caucasian” men. Being older and lower homonegativity scores were independently associated with finding all ethnic and racial types attractive. Being attracted only to “Caucasian” men was associated with younger age. Mental health was not associated with ethnic or racial partner preferences. Although men more commonly found most racial or ethnic types attractive, racial biases in partner selection were more evident among younger men, and among those who were less comfortable with their own sexuality. Addressing anti-gay stigma and broader exposure to gay community subcultures may be as important in countering racial bias.

Pre-exposure prophylaxis (PrEP) has been rapidly rolled out in large, publicly funded implementation projects in Victoria and New South Wales, Australia. Using behavioural surveillance of gay and bisexual men, we analysed the uptake and effect of PrEP, particularly on condom use by gay and bisexual men not using PrEP.We collected data from the Melbourne and Sydney Gay Community Periodic Surveys (GCPS), cross-sectional surveys of adult gay and bisexual men in Melbourne, VIC, and Sydney, NSW. Recruitment occurred at gay venues or events and online. Eligible participants were 18 years or older (face-to-face recruitment) or 16 years or older (online recruitment), identified as male (including transgender participants who identified as male); and having had sex with a man in the past 5 years or identified as gay or bisexual, or both. Using multivariate logistic regression, we assessed trends in condom use, condomless anal intercourse with casual partners (CAIC), and PrEP use by gay and bisexual men, controlling for sample variation over time.Between Jan 1, 2013, and March 31, 2017, 27 011 participants completed questionnaires in the Melbourne (n=13 051) and Sydney (n=13 960) GCPS. 16 827 reported sex with casual male partners in the 6 months before survey and were included in these analyses. In 2013, 26 (1%) of 2692 men reported CAIC and were HIV-negative and using PrEP, compared with 167 (5%) of 3660 men in 2016 and 652 (16%) of 4018 men in 2017 (p0·0001). Consistent condom use was reported by 1360 (46%) of 2692 men in 2013, 1523 (42%) of 3660 men in 2016, and 1229 (31%) of 4018 men in 2017 (p0·0001). In 2013, 800 (30%) of 2692 men who were HIV-negative or untested and not on PrEP reported CAIC, compared with 1118 (31%) of 3660 men in 2016, and 1166 (29%) of 4018 in 2017 (non-significant trend).A rapid increase in PrEP use by gay and bisexual men in Melbourne and Sydney was accompanied by an equally rapid decrease in consistent condom use. Other jurisdictions should consider the potential for community-level increases in CAIC when modelling the introduction of PrEP and in monitoring its effect.Australian Government Department of Health, Victorian Department of Health and Human Services, and New South Wales Ministry of Health.

The number of poly-drug users who mix use heroin and synthetic drugs (SD) is increasing worldwide. The objective of this study is to measure the risk factors for being infected with hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis among SD-only users, heroin-only users and poly-drug users. A cross-sectional study was conducted in 2015 from a national HIV surveillance site in Southwest China, 447 poly-drug, 526 SD-only and 318 heroin-only users were recruited. Poly-drug users have higher drug-use frequency, higher rates of drug-sharing and unsafe sexual acts than other users (p p

The acetylcholine muscarinic 4 (M4) receptor is a principal muscarinic receptor subtype present in the striatum. Notably, G(αi/o)-coupled M4 receptors and G(αs)/G(olf)-coupled dopamine D1 receptors are coexpressed in striatonigral projection neurons and are thought to interact with each other to regulate neuronal excitability, although underlying molecular mechanisms are poorly understood. In this study, we investigated the role of M4 receptors in the regulation of phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the rat normal and dopamine-stimulated striatum in vivo. We found that a systemic injection of a M4 antagonist tropicamide increased AMPA receptor GluA1 subunit phosphorylation at a protein kinase A-dependent site (S845) in the striatum. The tropicamide-induced S845 phosphorylation was rapid, reversible, and dose-dependent and occurred in the two subdivisions of the striatum, i.e., the caudate putamen and nucleus accumbens. Coadministration of subthreshold doses of tropicamide and a D1 agonist SKF81297 induced a significant increase in S845 phosphorylation. Coadministered tropicamide and a dopamine psychostimulant amphetamine at their subthreshold doses also elevated S845 phosphorylation. Tropicamide alone or coinjected with SKF81297 or amphetamine had no effect on GluA1 phosphorylation at S831. Tropicamide did not affect GluA2 phosphorylation at S880. These results reveal a selective inhibitory linkage from M4 receptors to GluA1 in S845 phosphorylation in striatal neurons. Blockade of the M4-mediated inhibition significantly augments constitutive and dopamine-stimulated GluA1 S845 phosphorylation.

Fyn is a member of the Src family of nonreceptor tyrosine kinases and is broadly expressed in the CNS. As a synapse-enriched kinase, Fyn interacts with and phosphorylates local substrates to regulate synaptic transmission and plasticity, although our knowledge of specific targets of Fyn at synaptic sites remains incomplete and the accurate role of Fyn in regulating synaptic proteins is poorly understood. In this study, we initiated an effort to explore the interaction of Fyn with a metabotropic glutamate receptor (mGluR). We found that recombinant Fyn directly binds to mGluR1a at a consensus binding motif located in the intracellular C-terminus (CT) of mGluR1ain vitro. Similarly, endogenous Fyn interacts with mGluR1a in adult rat cerebellar neuronsin vivo. Active Fyn phosphorylates mGluR1a at a conserved tyrosine residue in the CT region. In cerebellar neurons and transfected HEK293T cells, the Fyn-mediated tyrosine phosphorylation of mGluR1a is constitutively active and acts to facilitate the surface expression of mGluR1a and to potentiate the mGluR1a postreceptor signaling. These results support mGluR1a to be a novel substrate of Fyn. Fyn, by binding to and phosphorylating mGluR1a, potentiates surface expression and signaling of the receptors.

The use of antiretroviral therapy to prevent HIV transmission is now advocated in many settings, yet little research has documented the views of people with HIV. Semi-structured interviews were conducted in Australia between 2012 and 2014 with 27 HIV-positive people not using treatment at the time of interview. Thematic analysis of views on treatment-as-prevention found that while many participants recognised potential prevention benefits, only a minority was in support of initiating treatment solely to achieve those benefits. A range of uncertain or critical views were expressed regarding who would benefit, risk reduction, and changing treatment norms. Participants resisted responsibility narratives that implied treatment should be used for the public good, in favour of making considered decisions about their preferred approach to managing HIV. Engaging communities in dialogue and debate regarding the risks and benefits of treatment will be critical if this new prevention strategy is to engender public trust.

Previous research indicates that stigma and discrimination have negative consequences for both healthcare delivery and for health outcomes of people who inject drugs (PWID). Also important but not as well researched is the association between perceived discrimination and increased engagement in risky behaviours. This research aimed to explore whether perceived discrimination from workers in Needle and Syringe programmes (NSPs) is associated with increased engagement in injecting risk practices such as the sharing of injecting equipment.Convenience sampling was used across eight NSP sites within Western Sydney, Australia. All clients who attended one of the NSPs were eligible to participate.A total of 236 clients completed the survey. Perceived discrimination from NSP staff was found to be significantly associated with some injecting risk practices. Respondents who reported greater perceived discrimination from NSP staff were significantly more likely to report being injected by someone else after they had injected themselves (OR 1.2, 95%CI 1.1-1.3) and reusing a needle or syringe (OR 1.1, 95%CI 1.0-1.3) in the last month. Although clients reported perceiving more discrimination from general health workers than from NSP workers (12.8 vs. 10.2, t=7.739, df=226, p0.001), perceived discrimination from general health workers was not associated with increased injecting risk practices.The findings of this study suggest that NSP workers need to be aware that although they work in a model that is usually non-judgemental, their clients may still have a heightened sensitivity to discrimination which can then have consequences for on-going engagement in risk practices.

usc Introduction: We conducted a detailed analysis of trends in new HIV diagnoses in Australia by country of birth, to understand any changes in epidemiology, relationship to migration patterns and implications for public health programs. Methods: Poisson regression analyses were performed, comparing the age-standardised HIV diagnosis rates per 100,000 estimated resident population between 2006–2010 and 2011–2015 by region of birth, with stratification by exposure (male-to-male sex, heterosexual sex–males and females). Correlation between the number of permanent and long-term arrivals was also explored using linear regression models. Results: Between 2006 and 2015, there were 6,741 new HIV diagnoses attributed to male-to-male sex and 2,093 attributed to heterosexual sex, with the proportion of diagnoses attributed to male-to-male sex who were Australian-born decreasing from 72.5% to 66.5%. Compared with 2006–2010, the average annual HIV diagnosis rate per 100,000 in 2011–15 attributed to male-to-male sex was significantly higher in men born in South-East Asia (summary rate ratio (SRR) = 1.37, p = 0.001), North-East Asia (SRR = 2.18, p

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is a major ionotropic glutamate receptor subtype in the mammalian brain. Like other glutamate receptors, the AMPA receptor is regulated by phosphorylation. By phosphorylating specific serine resides in AMPA receptor subunits (GluA1 and GluA2), various protein kinases regulate subcellular/subsynaptic expression and function of the receptor. In this study, we conducted a time course study to evaluate the temporal property of responses of phosphorylation at those sites to dopamine stimulation with the psychostimulant amphetamine in the adult rat striatum and medial prefrontal cortex (mPFC) in vivo. We focused on biochemically-enriched AMPA receptors from synaptic and extrasynaptic compartments. We found that acute injection of amphetamine induced a rapid and relatively sustained increase in GluA1 S845 phosphorylation at both synaptic and extrasynaptic sites in the striatum. Similar results were observed in the mPFC. In contrast to S845, amphetamine did not induce a significant change in GluA1 S831 phosphorylation in synaptic and extrasynaptic pools in the striatum and mPFC. GluA2 S880 phosphorylation in synaptic and extrasynaptic fractions in the two brain regions also remained stable in response to amphetamine. These results support S845 to be a principal site on AMPA receptors sensitive to acute stimulant exposure. Its phosphorylation levels are rapidly upregulated by amphetamine in the two defined subsynaptic microdomains (synaptic versus extrasynaptic locations) in striatal and cortical neurons.

Objectives To analyse changes in testing for sexually transmissible infections (STI) among gay and bisexual men in Melbourne, Sydney and Queensland, Australia, particularly comprehensive STI testing (at least four tests from different anatomical sites in the previous year), and the characteristics of men who had such testing. Method Data were analysed from repeated, cross-sectional, community-based surveys conducted during 2003–2012. Trends in specific STI tests and comprehensive testing were assessed and the characteristics of participants who reported comprehensive STI testing were identified using multivariate logistic regression, stratified by HIV status. Results Among HIV-negative and unknown status men (n=51 009), comprehensive STI and HIV testing increased substantially from 13% in 2003 to 34% in 2012. During the same period, comprehensive STI testing (excluding HIV testing) increased from 24% to 57% among HIV-positive men (n=5532). In both HIV status groups, comprehensive testing was more commonly reported by men who had unprotected anal intercourse with casual partners, and men with higher numbers of partners. Among HIV-negative/unknown status participants, comprehensive STI and HIV testing was also associated with education level, regional location and finding partners online. Among HIV-positive men, comprehensive STI testing was also associated with free time spent with gay men and illicit drug use. Comprehensive testing was related to a high annual rate of diagnosis with STIs (20% of HIV-negative/unknown status men and 38% of HIV-positive men). Conclusions There has been a substantial improvement in the proportion of gay and bisexual men in Melbourne, Sydney and Queensland who report comprehensive testing. Comprehensive testing is most likely among men whose practices put them at increased risk of infection, and is associated with a high rate of STI diagnosis. However, opportunities for comprehensive testing are still being missed, suggesting a need for its ongoing promotion.

The AMPA receptor is regulated by phosphorylation. Two major phosphorylation sites (S831 and S845) are located in the intracellular C-terminal tail of GluA1 subunits. The phosphorylation on these sites controls receptor expression and function and is subject to the regulation by psychostimulants. In this study, we further characterized the regulation of S831 and S845 phosphorylation by amphetamine (AMPH) in the adult rat striatum and medial prefrontal cortex (mPFC) in vivo. We focused on the specific fraction of GluA1/AMPA receptors enriched from synaptic and extrasynaptic membranes, using a pre-validated biochemical fractionation procedure. We found that acute AMPH administration elevated GluA1 S845 phosphorylation in the defined synaptic membrane from the striatum in a dose-dependent manner. AMPH also induced a comparable increase in S845 phosphorylation in the extrasynaptic fraction of striatal GluA1. Similar increases in S845 phosphorylation in both synaptic and extrasynaptic pools were observed in the mPFC. In contrast, S831 phosphorylation was not altered in synaptic and extrasynaptic GluA1 in striatal neurons and synaptic GluA1 in mPFC neurons in response to AMPH, although a moderate increase in S831 phosphorylation was seen in extrasynaptic GluA1 in the mPFC after an AMPH injection at a high dose. Total synaptic and extrasynaptic GluA1 expression remained stable in the two regions after AMPH administration. Our data demonstrate the differential sensitivity of S845 and S831 phosphorylation to dopamine stimulation. S845 is a primary site where phosphorylation of GluA1 is upregulated by AMPH in striatal and mPFC neurons at both synaptic and extrasynaptic compartments.

BACKGROUND We aimed to describe the current use of antiretrovirals(ARVs) before unprotected anal intercourse (UAI) among Australian gay men, which may represent informal HIV preexposure prophylaxis (PrEP). METHODS Using data from Australian Gay Community Periodic Surveys conducted in 2011, we assessed the preventive use of ARVs before UAI and its association with sociodemographic characteristics, sexual practices, and drug use in the preceding 6 months. Associations were assessed using multivariate logistic regression analysis. RESULTS Of 3677 sexually active non-HIV-positive men, 2.5%reported taking ARVs before UAI. The likelihood of ARV use before UAI was significantly higher if any of the following behaviors were also reported: .1 sex partner; UAI with casual partners, irrespective of reporting UAI with regular partners [adjusted odds ratio (AOR) = 2.36; 95% confidence interval (CI): 1.24 to 4.48] or not (AOR = 2.71; 95% CI: 1.44 to 5.07); injecting drugs at least monthly (AOR = 2.56; 95% CI: 1.03 to 6.36); using “party” drugs,occasionally (AOR = 2.23; 95% CI: 1.33 to 3.73) or regularly(AOR = 5.34; 95% CI: 2.99 to 9.56); and group sex while using party drugs, occasionally (AOR = 2.42; 95% CI: 1.29 to 4.53) or regularly (AOR = 5.31; 95% CI: 2.62 to 10.76). Among non-HIV positive men in regular relationships with HIV-positive partners or partners of unknown HIV status, 1.7% and 4.7%, respectively, reported preventive ARV use before UAI. CONCLUSIONS Our findings illustrate sporadic use of ARVs before UAI among gay men in Australia, which was associated with high-risk casual sex and party drug use. These initial data contribute to a much needed understanding of the informal use of ARVs for HIV prevention.

Injecting drug use is commonly reported among gay and bisexual men in Australia. We examined the prevalence and covariates of injecting drug use among men participating in the Sydney Gay Community Periodic Survey between 2004-06 and 2011. In 2004-06, data was collected about which drugs were injected, while in 2011, data was collected about hepatitis C (HCV) and esoteric sexual practices. In 2004-06, 5.6 % of men reported injecting drugs in the previous 6 months; 3.4 % reported methamphetamine injection and 0.4 % heroin injection. In 2011, men who injected drugs were less likely to be employed full-time, and more likely to be HCV-positive, HIV-positive, to have used party drugs for sex, and to have engaged in esoteric sexual practices. The strong associations between injecting drug use, sexual risk practices and blood-borne virus infection suggests the need for combined sexual health and harm reduction services for gay and bisexual men who inject drugs.