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Background: Despite high levels of equipment distribution through Needle and Syringe Programmes (NSPs) in Australia, the levels of reuse of equipment among people who inject drugs remain concerning. This paper used an exploratory analysis to examine the needs of NSP client that could be addressed by NSPs to enhance service impact and blood-borne virus risk practices. Methods: People who inject drugs were recruited from six NSP sites in Sydney, Australia, to undertake a self-completed survey. Results: Using the responses of 236 NSP client participants, three factors were identified in an exploratory factor analysis: recent risky injection (Eigenvalue 3.63, 20.2 % of variance); disadvantage and disability (Eigenvalue 2.26, 12. 5 % of variance); and drug use milieu (Eigenvalue 1.50, 8.4 % of variance). To understand the distribution of these factors, the standardised factor scores were dichotomised to explore those participants with 'above average' vulnerability on each factor. A small group of NSP clients reported a cluster of vulnerability measures. Most participants (55.5 %) reported vulnerability on none or only one factor, indicating that 45.5 % could be considered as having double (35.6 %) or triple (8.9 %) vulnerability. Conclusions: These results challenge NSPs to understand the heterogeneity among their client group and develop programmes that respond to their clients' range of needs beyond those immediately associated with blood-borne virus (BBV) risk. This paper contributes to the growing evidence base regarding the need for BBV prevention efforts to examine strategies beyond equipment distribution. [ABSTRACT FROM AUTHOR]

Introduction. Sexual expression affects physical, mental and social well-being. There is a lack of understanding of male sexual dysfunction in homosexually active men. Aim. We investigated gay men's self-report of a number of sexual problems. Methods. The survey data were from a sample of 542 self-identified gay men, 40% of whom were HIV positive, recruited from six high HIV-caseload general practices in Australia. Main Outcome Measures. The reporting of experiencing three or more sexual problems over a period of at least 1 month in the 12 months prior to a survey was defined here as having “multiple” sexual problems. We explored a number of factors, including HIV status, depression, alcohol and other drug use, and sexual risk-taking with casual male partners, in association with multiple sexual problems. Results. Rates of a range of self-reported sexual problems were high, with erectile dysfunction and lack of sexual desire being the most commonly reported. These high rates were consistent with the limited data from previous Australian studies. Men who had multiple sexual problems were likely to suffer from major depression ( P < 0.001). A higher proportion of the HIV-positive gay men (48.4%) reported multiple sexual problems than the HIV-negative men (35.1%, P = 0.002). Factors independently associated with multiple sexual problems among the HIV-negative gay men were poorer general health and interpersonal isolation, whereas for the HIV-positive gay men, they were adoption of avoidant strategies to cope with daily life stress, sexual risk-taking in casual encounters, and the use of antidepressants. Conclusions. Our findings underscore the complex interactions between depression, sexual dysfunction, sexual risk taking, HIV infection, and general well-being among homosexually active men. Mao L, Newman CE, Kidd MR, Saltman DC, Rogers GD, and Kippax SC. Self-reported sexual difficulties and their association with depression and other factors among gay men attending high HIV-caseload general practices in Australia. J Sex Med 2009;6:1378–1385. [ABSTRACT FROM AUTHOR]

The parvicellular part of the ventroposteromedial nucleus of the thalamus (VPMpc) is positioned at the key site between the gustatory parabrachial nuclei (PbN) and the gustatory cortex for relaying and processing gustatory information via the thalamocortical pathway. Although neuroanatomi- cal and electrophysiological studies have provided information re- garding the gustatory projection from PbN to VPMpc, the exact relationship between PbN and VPMpc, especially the efferent projection involving VPMpc to PbN, is obscure. Here we investigated the reciprocal connection between these two gustatory relays in urethane-anesthetized hamsters. We recorded from 114 taste-responsive neurons in the PbN and examined their responsiveness to electrical stimulation of the VPMpc bilaterally. Stimulation of either or both of the ipsilateral or contralateral VPMpc antidromically activated 109 gustatory PbN neurons. Seventy-two PbN neurons were antidromically activated after stimulation of both sides of the VPMpc, indicating that taste neurons in the PbN project heavily to the bilateral VPMpc. Stimulation of VPMpc also orthodromically activated 110 of PbN neurons, including 106 VPMpc projection neurons. Seventy- eight neurons were orthodromically activated bilaterally. Among orthodromic activations of the PbN cells, the inhibitory response was the dominant response; 106 cells were inhibited, including 10 neurons that were also excited contralaterally, indicating that taste neurons in the PbN are subject to strong inhibitory control from VPMpc. Moreover, stimulation of VPMpc altered taste responses of the neurons in the PbN, indicating that VPMpc modulates taste responses of PbN neurons. These results may provide functional insight of neural circuitry for taste processing and modulation involving these two nuclei. [ABSTRACT FROM AUTHOR]

Taste receptors on the left and right sides of the anterior tongue are innervated by chorda tympani (CT) fibers, which carry taste information to the ipsilateral nucleus of the solitary tract (NST). Although the anterior tongue is essential for taste, patients with unilateral CT nerve damage often report no subjective change in their taste experience. The standing theory that explains the taste constancy is the ‘release of inhibition’, which hypothesizes that within the NST there are inhibitory interactions between inputs from the CT and glossopharyngeal nerves and that the loss of taste information from the CT is compensated by a release of inhibition on the glossopharyngeal nerve input. However, the possibility of compensation by taste input from the other side of the tongue has never been investigated in rodents. We recorded from 95 taste-responsive neurons in the NST and examined their responsiveness to stimulation of the contralateral CT. Forty-six cells were activated, mostly with excitatory responses (42 cells). Activation of NST cells induced by contralateral CT stimulation was blocked by microinjection of lidocaine into the contralateral NST but was not affected by anesthetization of the contralateral parabrachial nuclei (PbN). In addition, the NST cells that were activated by contralateral CT stimulation showed reduced responsiveness to taste stimulation after microinjection of lidocaine into the contralateral NST. These results demonstrate that nearly half of the taste neurons in the NST receive gustatory information from both sides of the tongue. This ‘cross talk’ between bilateral NST may also contribute to the ‘taste constancy’. [ABSTRACT FROM AUTHOR]

Gαq-protein-coupled group I metabotropic glutamate receptors (mGluRs) are densely expressed in brain neurons and are actively involved in various cellular activities. In this study, we investigated the role of group I mGluRs in regulating the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase in cultured neurons. We found that selective activation of mGluR5 induced a rapid and transient phosphorylation of JNK. In a series of studies to determine the mechanisms, we found that the conventional mGluR5-associated signaling pathways (inositol-1,4,5-triphosphate-mediated Ca2+ release and activation of protein kinase C) were not involved in the mGluR5 regulation. Instead, ligand stimulation ofmGluR5caused a dynamic transactivation of the epidermal growth factor (EGF) receptor, which in turn triggered a downstream signaling pathway to upregulate JNK phosphorylation. Furthermore, the mGluR5-dependent JNK activation specifically activated c-Jun, but not activating transcription factor-2 or JunD, and increased activator protein-1 (AP-1)-mediated endogenous transcriptional activity. Together, we identified a novel mGluR5-to-nucleus communication through the EGF/JNK pathway, which functions to regulate AP-1-mediated transcription. [ABSTRACT FROM AUTHOR]

The regulation of protein phosphorylation requires coordinated interaction between protein kinases and protein phosphatases (PPs). Recent evidence has shown that the Gαq-protein-coupled metabotropic glutamate receptor (mGluR) 5 up-regulates phosphorylation of MAPK/ERK½. However, signaling mechanisms linking mGluR5 to ERK are poorly understood. In this study, roles of a major serine/threonine PP, PP2A, in this event were evaluated in cultured neurons. We found that the PP1/2A inhibitors okadaic acid and calyculin A mimicked the effect of the mGluR5 agonists (RS)-3,5-dihydroxyphenylglycine and (RS)-2-chloro-5-hydroxyphenylglycine in facilitating phosphorylation of ERK1/2 and its upstream kinase, MEK1/2, in a PP2A-dependent but not PP1-dependent manner. Co-administration of either inhibiter with an mGluR5 agonist produced additive phosphorylation of ERK1/2. Enzymatic assays showed a basal level of phosphatase activity of PP2A under normal conditions, and activation of mGluR5 selectively inhibited PP2A, but not PP1, activity. In addition, a physical association of the cytoplasmic C terminus of mGluR5 with PP2A was observed, and ligand activation of mGluR5 reduced mGluR5-PP2A binding. Additional mechanistic studies revealed that mGluR5 activation increased tyrosine (Tyr307) phosphorylation of PP2A, which was dependent on activation of a p60c-Src family tyrosine kinase, but not the epidermal growth factor receptor tyrosine kinase and resulted in dissociation of PP2A from mGinR5 and reduced PP2A activity. Together, we have identified a novel, mGluR5-triggered signaling mechanism involving use- and Src-dependent inactivation of PP2A, which contributes to mGliR5 activation of MEK1/2 and ERK1/2. [ABSTRACT FROM AUTHOR]

Group I metabotropic glutamate receptors (mGluRs) increase cellular levels of inositol-1,4,5-triphosphate (IP3) and thereby trigger intracellular Ca2+ release. Also, group I mGluRs are organized with members of Homer scaffold proteins into multiprotein complexes involved in postreceptor signaling. In this study, we investigated the relative importance of the IP3/Ca2+ signaling and novel Homer proteins in group I mGluR-mediated activation of extracellular signal-regulated protein kinases 1 and 2 (ERK½) in cultured rat striatal neurons. We found that selective activation of mGluR5, but not mGluR1, increased ERK½ phosphorylation. Whereas the IP3/Ca2+ cascade transmits a small portion of signals from mGluR5 to ERK½, the member of Homer family Homer1b/c forms a central signaling pathway linking mGluR5 to ERK½ in a Ca2+-independent manner. This was demonstrated by the findings that the mGluR5-mediated ERK½ phosphorylation was mostly reduced by a cell-permeable Tat-fusion peptide that selectively disrupted the interaction of mGluR5 with the Homer1b/c and by small interfering RNAs that selectively knocked down cellular levels of Homer1b/c proteins. Furthermore, ERK½, when only coactivated by both IP3/Ca2+ and Homer1b/c-dependent pathways, showed the ability to phosphorylate two transcription factors, Elk-1 and cAMP response element-binding protein, and thereby facilitated c-Fos expression. Together, we have identified two coordinated signaling pathways (a conventional IP3/Ca2+ vs a novel Homer pathway) that differentially mediate the mGluR5-ERK coupling in neurons. Both the Ca2+-dependent and -independent pathways are corequired to activate ERK½ to a level sufficient to achieve the mGluR5-dependent synapse-to-nucleus communication imperative for the transcriptional regulation. [ABSTRACT FROM AUTHOR]

The specification and organization of glutamatergic synaptic transmission require the coordinated interaction among glutamate receptors and their synaptic adaptor proteins closely assembled in the postsynaptic density (PSD). Here we investigated the interaction between NMDA receptors and metabotropic glutamate receptor 5 (mGluR5) in the integral regulation of extracellular signal-regulated protein kinase (ERK) and gene expression in cultured rat striatal neurons. We found that coapplication of NMDA and the mGluR5 agonist (S)-3,5-dihydroxyphenylglycine synergistically increased ERK phosphorylation. Interestingly, the synergistic increase in ERK phosphorylation was dependent on the cross talk between NMDA receptor-associated synaptic adaptor protein PSD-95 and the mGluR5-linked adaptor protein Homer1b/c but not on the conventional Ca2+ signaling derived from NMDA receptors (Ca2+influx) and mGluR5 (intracellular Ca2+ release). This was demonstrated by the findings that the synergistic phosphorylation of ERK induced by coactivation of NMDA receptors and mGluR5 was blocked by either a Tat peptide that disrupts NMDA receptor/PSD-95 binding or small interfering RNAs that selectively reduce cellular levels of Homer1b/c. Furthermore, ERK activated through this PSD-95/Homer1b/c-dependent and Ca2+-independent pathway was able to phosphorylate the two key transcription factors Elk-1 and cAMP response element-binding protein, which further leads to facilitation of c-Fos expression. Together, we have identified a novel Ca2+-independent signaling pathway to ERK by the synergistic interaction of NMDA receptors and mGluR5 via their adaptor proteins in the PSD of neurons, which underlies a synapse-to-nucleus communication important for the transcriptional regulation. [ABSTRACT FROM AUTHOR]

Presents a cross-sectional survey on the sexual practices of gay men of Asian background in Sydney, New South Wales. Increase in unprotected anal intercourse (UAI) among gay community in the region; Proportion of gay Asian men with UAI experiences; Introduction of highly active antiretroviral therapies for possible HIV outbreak in the gay community.

SUMMARY: BACKGROUND The mechanism of the antagonistic hemodynamic interaction between ethanol and centrally acting sympatholytics is not known. In this study, we tested the hypothesis that the imidazoline (I1)-receptor modulation of norepinephrine (NE) release within the rostral ventrolateral medulla (RVLM) plays a pivotal role in this clinically relevant hemodynamic interaction.METHOD In anesthetized spontaneously hypertensive rats, the effects of centrally acting sympatholytics on RVLM NE electrochemical signal were investigated by in vivo electrochemistry along with cardiovascular responses in the absence and presence of ethanol. In vivo microdialysis in conscious spontaneously hypertensive rats was used to confirm the electrochemical findings.RESULTS Clonidine (30 μg/kg, intravenously) or rilmenidine (400, 600, or 800 μg/kg) significantly reduced RVLM NE electrochemical signal (index of neuronal activity) and mean arterial pressure; rilmenidine effects were dose-related, and ethanol (1 g/kg) counteracted these responses. Ethanol (1 g/kg) pretreatment increased both RVLM NE electrochemical signal and blood pressure but did not influence the reductions in both variables elicited by subsequently administered clonidine. The α2-adrenergic antagonist 2-methoxyidazoxan (30 μg/kg) counteracted rilmenidine (800 μg/kg)-evoked responses. In vivo microdialysis in conscious spontaneously hypertensive rats confirmed the electrochemical findings since clonidine- (30 μg/kg, intravenously) evoked reductions in RVLM NE and the associated hypotension were counteracted by ethanol (1 g/kg).CONCLUSIONS (1) Ethanol counteracts centrally mediated hypotension, at least in part, by increasing RVLM NE; (2) the interaction involves the I1 receptor modulation of RVLM neuronal activity; (3) the α2-adrenergic receptor contributes to the electrochemical and cardiovascular effects of high doses of rilmenidine, and (4) the RVLM is a neuroanatomical target for systemically administered ethanol. [ABSTRACT FROM AUTHOR]

As social robots may be used by a single user or multiple users different social scenarios are becoming more important for defining human-robot relationships. Therefore, this study explored human-robot relationships between robots and users in different interaction modes to improve user interaction experience. Specifically, education and companion were selected as the most common areas in the use of social robots. The interaction modes used include single-user interaction and multiuser interaction. The three human-robot relationships were adopted. The robot competence scale, human-robot trust scale, and acceptance of robot scale were used to evaluate subjects' views on robots. The results demonstrate that in the two scenarios, people were more inclined to maintain a more familiar and closer relationship with the social robot when the robot interacted with a single user. When multiple persons interact in an education scenario, setting the robot to Acquaintance relationships is recommended to improve its competence and people's trust in the robot. Similarly, in multi-person interaction, Acquaintance relationships would be more accepted and trusted by people in a companion scenario. Based on these results, robot sensors can be added to further optimize human-robot interaction sensing systems. By identifying the number of users in the interaction environment, robots can automatically employ the best human-robot relationship for interaction. Optimizing human-robot interaction sensing systems can also improve robot performance perceived in the interaction to meet different users' needs and achieve more natural human-robot interaction experiences. [ABSTRACT FROM AUTHOR]

Smoking is an important factor that causes periodontitis, which manifests as alveolar bone injury and absorption, and has a high incidence and unfavorable treatment efficacy. Nicotine causes ischemia and inflammation of the periodontium and inhibits the mineralization of alveolar bones. Previous studies have revealed the anti-tumor biological activities of catalpol, in addition to neuroprotection and anti-inflammation. The present study therefore investigated the underlying protective mechanism of catalpol in alveolar bone injury. A total of 24 Wistar rats were infused with nicotine (0.7 mg/kg for 30 days), followed by subcutaneous injection of catalpol (2 μg/kg for 14 days). The loss of alveolar bone was examined, and bone alkaline phosphatase (AP) and osteocalcin levels were examined by ELISA. The expression of tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2) was quantified by reverse transcription-quantitative polymerase chain reaction analysis and western blotting. Treatment with nicotine decreased AP and osteocalcin levels, increased TNF-α and COX-2 expression levels, and led to alveolar bone loss compared with the control group. Catalpol decreased bone loss, increased AP and osteocalcin, and decreased TNF-α and COX-2 expression compared with the nicotine treatment group. Catalpol may alleviate nicotine-induced injury and alveolar bone loss via inhibition of inflammatory factors, and facilitate the mineralization of alveolar bones. [ABSTRACT FROM AUTHOR]

This article reports on in-depth interviews with gay men about their experiences and understanding of depression. It is a key outcome of the collaboration between social researchers, general practitioners and community partners to investigate the management of depression in gay men in primary care settings. As part of the qualitative arm of the project in-depth interviews were conducted with 40 gay men in Sydney and Adelaide (Australia). The approach to discourse analysis is informed by Hallidayan systemic functional linguistics. Six constructions of depression were identified: (1) depression as a constellation of symptoms; (2) symptoms constructed as experience; (3) depression as agent; (4) depression as mental processes; (5) not meeting social expectations; and (6) engaging with psychiatric discourse: constructing alternative positions. Gay men draw on the biomedical model of depression as low mood and loss of pleasure as well as on constructions of depression in terms of social experience. The biomedical model of depression is, however, not positioned as unproblematic. Rather, gay men align or disalign with this discourse according to their own experience, thereby enacting diverse masculinities. Gay men’s discourses of depression are inextricably linked to the community activism of gay men and their community organizations in the context of the HIV epidemic, as well as a synergy between gay men and their doctors. [ABSTRACT FROM PUBLISHER]

Background. Despite increasing reports of herpes simplex virus (HSV) type 1 (HSV-1)-associated anogenital herpes, there are very limited data comparing the seroepidemiological profile of and risk factors for HSV-1 and 0HSV type 2 (HSV-2) infection. Methods. Sexual behaviors were examined as risk factors for prevalent and incident HSV-1 and HSV-2 infections in a community-based cohort of 1427 HIV-negative gay men in Australia. Results. The prevalence of HSV-1 and HSV-2 at baseline was 75% and 23%, respectively. The rate of prevalent infection with HSV-1, as well as the rate of prevalent infection with HSV-2, was much lower in individuals <25 years of age, and each type of infection was associated with a higher number of both male and female sex partners. The median duration of follow-up of the cohort was 2.0 years. Among participants who were susceptible to infection, the incidence rates for HSV-1 and HSV-2 infection were 5.58 and 1.45 cases per 100 person-years, respectively. In multivariate analysis, incident infection with HSV-1 was significantly associated with younger age (P =.027) and reports of frequent insertive oral sex with casual partners (hazard ratio, 3.91 [95% confidence interval, 1.23–12.44]; P = .021 ). Incident infection with HSV-2 was significantly associated with a variety of anal sex practices with casual partners. Conclusions. Both HSV-1 and HSV-2 were commonly sexually transmitted, and there were more HSV-1 than HSV-2 seroconversions. Public-health strategies targeted against anogenital herpes increasingly need to take into account the importance of HSV-1 infection. [ABSTRACT FROM AUTHOR]

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, crosssectional 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--HIVpositive 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, 0.001), awareness increased from 29.6% (563/1901) to 87.1% (2555/2935; P, 0.001), and PrEP use increased from 3.7% (21/563) to 45.2% (1155/2555; P, 0.001). Of 1038 non--HIV-positive men in the PrEPARE Project in 2017, 54.2% (n = 563) were eligible for PrEP, 97.2% (547/563) were aware, 67.6% (370/547) were willing to use PrEP, 73.5% (272/370) had discussed PrEP with a doctor, 78.3% (213/272) were using PrEP, 97.2% (207/213) had recently tested, and 75.8% (157/207) reported reduced HIV concern and increased pleasure because of PrEP. The break point analyses indicated that PrEP coverage was affected by geographical availability, education level, employment, and willingness to use PrEP. Conclusions: PrEP eligibility, awareness, and use have rapidly increased among Australian gay and bisexual men. The cascades identify disparities in uptake by eligible men as a result of socioeconomic factors and PrEP's acceptability [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to calculate the cost of a range of needle and syringe program (NSP) models to contribute to planning for effective NSP delivery. Existing health service data was used to estimate the cost per needle distributed across four modes of service delivery (Primary NSP, including one model of Primary NSP providing primary health care; Secondary NSP; Vending Machine and Outreach) over three years. Costs were primarily affected by the ratio of the volume of equipment distributed to staff costs. The average cost per unit for Primary, Secondary and Outreach modes was approximately $1.00. The cost for Vending Machine provision (accounting for income from service users) was the cheapest option at $0.30-0.40 per unit. When income from services users are not included in calculations, other considerations may be more important than cost when making decisions about providing access to NSP services to a marginalized client group with diverse needs. [ABSTRACT FROM AUTHOR]

Background. In contrast to the broad literature on depression in the general population, little is known about the management of depression affecting gay men and HIV-positive men attending general practice clinics. Objective. This paper explores qualitative descriptions of how depression in gay men and HIV-positive men is managed by GPs. Methods. As part of the qualitative component of a mixed method study on HIV and depression, semi-structured interviews were conducted with 16 GPs in three geographical settings in Australia: Sydney, Adelaide and a rural coastal town. Results. GPs identified a range of features in their experience of managing depression in gay men and in HIV-positive men. Some were common to the care of other groups with depression, but this paper reports on features unique to this patient group. These include capitalizing on the high frequency of contact with this patient group, taking advantage of the specialist multidisciplinary teams who provide support, building upon the unusual willingness of this patient group to take medication, appreciating the central importance to many gay men of sexual functioning, and recreational drug use, responding to social isolation in this patient group and coping with increasing challenges for the HIV general practice workforce. Conclusions. Despite the identification of several key strengths in working with this patient group, the ability of GPs to develop their capacity to manage depression in gay men and men with HIV is uncertain in the context of a growing range of challenges for GPs in both mental health and HIV care. [ABSTRACT FROM AUTHOR]

The hydrophobic block of polymeric micelles formed by amphiphilic copolymers has no direct therapeutical effect, and the metabolites of these hydrophobic segments might lead to some unexpected side effects. Here the hydrophobic core of polymeric micelles is replaced by highly water-insoluble drugs themselves, forming a new micellar drug delivery system. By grafting hydrophobic drugs of paclitaxel (PTX) onto the surface of hydrophilic hyperbranched poly(ether-ester) (HPEE), we constructed an amphiphilic copolymer (HPEE-PTX). HPEE-PTX could self-assemble into micellar nanoparticles in aqueous solution with tunable drug contents from 4.1 to 10.7%. Moreover, the hydrolysis of HPEE-PTX in serum resulted in the cumulative release of PTX. In vivo evaluation indicated that the dosage toleration of PTX in mice had been improved greatly and HPEE-PTX micellar nanoparticles could be used as an efficient prodrug with satisfactory therapeutical effect. We believe that most of the lipophilic drugs could improve their characters through this strategy. [ABSTRACT FROM AUTHOR]

Activation of group I metabotropic glutamate receptors (mGluRs) up-regulates transcription factor cyclic AMP response element-binding protein (CREB) and Elk-1 phosphorylation via extracellular signal-regulated kinase 1/2 (ERK1/2) in the striatum in vivo . Protein phosphatase 1/2A further regulates immediate early gene expression by inactivating (dephosphorylating) CREB. In this study, using semi-quantitative immunohistochemical and western blot analyses and in situ hybridization histochemistry, we found that intrastriatal infusion of the protein phosphatase 1/2A inhibitor okadaic acid (0.005, 0.05 and 0.5 nmol) increased CREB and Elk-1 phosphorylation and c-Fos immunoreactivity in the injected dorsal striatum in a dose-dependent manner. In addition, okadaic acid (0.05 and 0.5 n m ) increased c- fos mRNA expression in the dorsal striatum in a dose-dependent manner. Intrastriatal infusion of the group I agonist 3,5-dihydroxyphenylglycine (DHPG) at 100 and 250 n m also increased CREB and Elk-1 phosphorylation. Pre-treatment of okadaic acid (0.05 n m ) did not alter DHPG-induced increases in the phosphorylation of the two transcription factors. These data suggest that protein phosphatase 1/2A in striatal neurons is tonically active in dephosphorylating CREB and Elk-1 and thus suppressing constitutive c- fos mRNA and protein expression. Inhibition of the phosphatase 1/2A may contribute to the group I mGluR-regulated phosphorylation of these transcription factors and c-fos expression. [ABSTRACT FROM AUTHOR]