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Abstract Introduction Hepatitis B is a significant public health concern and a leading cause of liver cancer across the world. In Australia, hepatitis B is largely endemic in migrant communities, particularly amongst the Chinese and Vietnamese communities. Negative attitudes towards hepatitis B can be a major barrier to hepatitis B testing and linkage to care. This mixed-methods research explores the attitudes and beliefs, including stigma, about hepatitis B among students of Vietnamese and Chinese background in Australia. Students were chosen as participants as there is little research examining hepatitis B among university students in Australia and they provide a point of entry to communities with high prevalence of hepatitis B, that otherwise may be hard to access. Methods Online surveys were distributed in Chinese, Vietnamese, and English via social media and completed by 112 students of Chinese and 95 students of Vietnamese backgrounds. In-depth interviews were also conducted with 13 Vietnamese and 10 Chinese participants to further explore the survey results. Results Survey findings suggest that students have varied attitudes towards people living with hepatitis B. Around half of the participants reported they would behave negatively towards other people with hepatitis B and that they would expect to experience stigma or discrimination if they had hepatitis B. While over 70% in both samples reported that people who have hepatitis B should not be isolated by family and friends, 47.6% of the Chinese sample and 28.3% of the Vietnamese sample reported they would avoid close contact with someone with hepatitis B. The qualitative data expands on the quantitative data. Four key themes were identified: (1) Caution not discrimination (2) Hepatitis B as a sign of immoral behaviour (3) Discriminatory behaviour based on perceived effects of hepatitis B and (4) Shifting attitudes. Conclusion This research provides insights that could inform culturally sensitive health promotion programs to address negative attitudes towards hepatitis B among the broader Chinese and Vietnamese communities living in Australia.

Abstract Background Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. “EMERALD” is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. Methods The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. Discussion This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector’s contribution to addressing the growing burden of non-communicable diseases in China. Trial registration The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024).

Abstract Introduction HIV pre‐exposure prophylaxis (PrEP) has been publicly available since 2018 in Australia as a daily regimen. In 2019, clinical guidelines were updated to support guidance on event‐driven PrEP (ED‐PrEP) use. We assessed trends in the PrEP dosing regimen by comparing daily PrEP use to ED‐PrEP among cisgender gay, bisexual and other men who have sex with men (GBMSM). Methods Data from repeated, cross‐sectional, national behavioural surveillance surveys were analysed from 2019 to 2023 among participants not living with HIV. Logistic regression models were conducted to assess trends and compared ED‐PrEP users to non‐PrEP users and daily PrEP. Results Among 38,880 participants, overall PrEP use with any regimen increased from 27.6% in 2019 to 42.7% in 2023 (OR = 1.16, 95% CI = 1.15−1.18, p < 0.001). Among 12,922 participants who reported PrEP use in the last 6 months, the proportion reporting ED‐PrEP use increased from 7.6% in 2019 to 27.8% in 2023 (OR = 1.41, 95% CI = 1.37−1.46, p < 0.001) with those who reported daily PrEP decreasing from 92.4% to 63.3% (OR = 0.64, 95% CI = 0.62−0.66, p < 0.001). In a cross‐sectional sub‐sample in 2022–2023 (n = 8840), compared to ED‐PrEP users, non‐PrEP users were less likely to have received three or more HIV tests in the last 12 months (aRRR = 0.26, 95% CI = 0.22−0.31, p < 0.001), have 2−10 male sexual partners in the last 6 months (aRRR = 0.24, 95% CI = 0.14−0.41, p < 0.001) or 11 or more (aRRR = 0.26, 95% CI = 0.15−0.45, p < 0.001) compared to none, or to report condomless anal intercourse with casual partners (aRRR = 0.38, 95% CI = 0.32−0.46, p < 0.001). Compared to ED‐PrEP users, daily PrEP users were more likely to have received three of more HIV tests in the last year (aRRR = 3.73, 95% CI = 3.15−4.40, p < 0.001) and less likely to be born overseas and lived in Australia for less than 5 years compared to being born in Australia (aRRR = 0.64, 95% CI = 0.49−0.83, p = 0.001). Conclusions While daily PrEP remains the most common PrEP dosing regimen among GBMSM in Australia, there has been a steep increase in the proportion of PrEP users who are taking ED‐PrEP. Monitoring of PrEP use should continue to adapt to new dosing methods and future PrEP options. As ED‐PrEP use increases, further work is needed to ensure those taking ED‐PrEP are taking it effectively to prevent HIV.

Abstract Background The prevalence of type 2 diabetes (T2DM) in China is over 10%, affecting around 114 million people. Despite the inclusion of T2DM in the National Basic Public Health Service Program (NBPHSP), most people with T2DM experience challenges in achieving optimal management targets. This study aimed to identify barriers and facilitators of diabetes management from the perspectives of primary health care (PHC) service providers and recipients. Methods This mixed-methods study was conducted in Shijiazhuang City, Hebei Province, China. A quantitative PHC facility assessment survey was conducted in all administrative districts and qualitative in-depth interviews were conducted in one district to government officials, medical staff, patients with T2DM, and their family members. Interviews were thematically analyzed, and all findings were synthesized using Michie’s COM-B theory. Results A total of 197 village/community level PHC facilities and 66 township/street level PHC facilities answered the survey, and 42 in-depth interviews were conducted. The key facilitators stemmed from the NBPHSP policy, which standardized the basic infrastructure, medical equipment, and medication for the PHC facilities, provided training on NCD prevention and control, and compensated the PHC workers. However, we identified a detrimental cycle among PHC providers characterized by inadequate capacity, overwhelming workloads, insufficient income, limited career development opportunities, and challenges in attracting young talents. Although patients were covered by the national medical insurance schemes, they experienced capability constraints primarily driven by low education levels, advanced age, low health literacy, and a proliferation of misinformation. These factors influenced patients’ motivation to be actively engaged in care and contributed to inertia to intensify treatment and achieve their clinical management goals. Conclusion This study identifies several major facilitators and barriers from the perspectives of both PHC providers and patients with T2DM. Our findings suggest there are substantial opportunities to strengthen the NBPHSP, including improving the capacity and the income level of the PHC providers, attracting and retaining skilled health workers in rural areas, supporting patients to improve their health literacy and take a more active role in their health care, and improving access to high-quality care through digital health approaches. Trial registration ClinicalTrials.gov (record NCT02726100, 03/22/2016).

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 multi-user 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.

Summary: Background: China’s National Essential Public Health Service Package (NEPHSP) aims to promote health for all at the primary health care level and includes a focus on hypertension and type-2 diabetes mellitus (T2DM). However, there are limited contemporary data to quantify the care cascades of hypertension and T2DM in primary health care. Methods: This cross-sectional study involved individual level linkage of routinely collected data from the NEPHSP, health insurance claims and hospital electronic health records, from four diverse regions in China, including Xiling District (central China), Wenchuan County (western), Acheng District and Jiao District (northern). We first compared numbers of people aged ≥35 with a recorded diagnosis of hypertension and T2DM against expected numbers derived from epidemiological data. We then constructed care cascades to assess the percentages (1) enrolled in the NEPHSP, (2) adherent to the follow-up care of NEPHSP, (3) receiving medication treatment, and (4) having hypertension and/or T2DM controlled. Findings: In the four regions, the total numbers of people aged ≥35 diagnosed of hypertension and T2DM from any data source were 149,176 and 50,828, respectively. This was estimated to be 46.0% (95% confidence interval [CI]: 45.8%–46.2%) and 45.6% (95% CI: 45.3%–45.9%) of the expected totals for hypertension and T2DM, respectively. Among those diagnosed, 65.4% (95% CI: 65.1%–65.6%) with hypertension and 66.1% (95% CI: 65.7%–66.5%) with T2DM were enrolled in the NEPHSP, respectively, in which 54.8% (95% CI: 54.5%–55.2%) with hypertension and 64.7% (95% CI: 64.1%–65.2%) with T2DM were adherent to the required services. Among those enrolled, the overall treatment rates were 70.8% (95% CI: 70.6%–71.1%) for hypertension and 82.2% (95% CI: 81.8%–82.6%) for T2DM. Among those treated, a further 80.9% (95% CI: 80.6%–81.2%) with hypertension and 73.9% (95% CI: 73.3%–74.4%) with T2DM achieved control. These results varied considerably across regions, with the northern sites showing relatively higher enrolment rates while the central site had higher control rates. Interpretation: Detection and control rates for hypertension and T2DM are suboptimal in these four regions of China. Further strategies are needed to improve people’s enrolment in and adherence to the NEPHSP and strengthen care delivery processes. Of note, our estimations of the diagnosis rates for each region are based on national level large epidemiological data. The interpretation of these data needs caution due to potential bias caused by regional variations. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757), and National Natural Science Foundation of China (72074065).

Abstract Introduction: Overseas‐born gay and bisexual men (GBM) are overrepresented in HIV diagnoses in Australia. We assessed social and sexual behaviours, and the use of HIV prevention and testing, by region of birth and length of residence in Australia. We sought to identify similarities and differences between recently arrived and non‐recently arrived GBM from non‐English‐speaking countries to improve targeting and engagement with HIV testing and prevention. Methods: Data were collected in national repeated, behavioural surveillance surveys conducted across Australia during 2019–2021. Logistic regression was used to identify factors that differentiated between recently arrived (

Summary: Pre-exposure prophylaxis (PrEP) is recommended for people susceptible to HIV acquisition, and the scale-up of PrEP programmes has contributed to new HIV case reductions at a population level. However, international migrants continue to be disproportionately affected by HIV. Understanding barriers and facilitators to PrEP implementation among international migrants can optimise PrEP use among this population and ultimately reduce HIV incidence worldwide. We reviewed the evidence regarding factors influencing PrEP implementation among international migrants; 19 studies were included. The barriers and facilitators at the individual level were related to knowledge and risk perception of HIV. Cost, provider discriminations, and health system navigation influenced PrEP use at the service level. Positive or negative perception towards LGBT+ identities, HIV, and PrEP users affected PrEP use at the societal level. Most existing PrEP campaigns do not target international migrants; therefore, culturally tailored approaches for people from different backgrounds are warranted. Potentially migration-related and HIV-related discriminatory policies must be reviewed to increase access to HIV prevention services to end HIV transmission at a population level.

The HIV epidemic in Australia is changing with higher risk for HIV among newly-arrived Asian-born men who have sex with men (MSM) compared to Australian-born MSM. We evaluated the preferences for HIV prevention strategies among 286 Asian-born MSM living in Australia for

Summary: Background: High antiretroviral therapy (ART) coverage and viral suppression among people with HIV (PWH) in Australia provide a unique context to study individual cognitive trajectories, cognitive aging and factors associated with longitudinal cognitive function during chronic and stable HIV disease. Methods: Participants from the Predictors of Adherence to Antiretroviral Therapy study (n = 457, recruited between September 2013 and November 2015, median age = 52 years, and all with HIV RNA 0.5). Meaningful cognitive change was statistically defined (decline or improvement versus stability, i.e., 90% CI, that is p

ObjectivesGay, bisexual and other men who have sex with men (GBMSM) and trans and gender diverse (TGD) people are disproportionately affected by poorer sexual health outcomes compared to heterosexual populations. We aimed to explore the preferences of GBMSM and TGD for using eHealth for sexual health (eSexualHealth).MethodsWe distributed an anonymous online survey from April to August 2021among the lesbian, gay, bisexual, transgender, intersex, queer and other people of diverse sexuality or gender (LGBTIQA+) community in Australia. The survey collected data on sociodemographic characteristics and sexual behaviors, their preferences for app/website functions and preferred HIV and sexually transmitted infection (STI) testing reminders. We used descriptive statistics to summarize the characteristics of the study population. Free-text responses were thematically analyzed.ResultsOf 466 participants included, most identified as cisgender males (92.7%). The median age was 48 [interquartile range (IQR): 37–56]. For accessing sexual health-related information, 160 (34.6%) would use either a website or an app, 165 (32.7%) would prefer a website, 119 (25.8%) would prefer an app, and 33 (7.1%) would not use either platform. There was no significant difference between GBMSM and TGD people. Participants were most interested in information about STI clinics, HIV/STI hotspots, and sexual health education. Participants stressed the need for privacy and anonymity when using eHealth. Regarding reminders to test for HIV/STIs, receiving regular SMS was most popular (112/293, 38.2%), followed by regular emails (55/293 18.8%) and a reminder function on their phone (48/293, 16.4%).ConclusionOur study suggests a promising future for eHealth among GBMSM and TGD people. Sexual health is still a stigmatized area, and eHealth may circumvent barriers this population faces.

BackgroundEarly intervention alcohol and drug (AOD) programs for disadvantaged young people have the potential to substantially decrease the need for future intervention, however there is little research about how young people use these programs or the substance use and other outcomes of such programs. This paper uses data from an Australian AOD early intervention program, The Street Universities, to: describe young people's participation; examine changes in substance use and wellbeing over 90 days; and assess which young people are most positively impacted.MethodsData come from a prospective study of new attendees, measuring retention in and attendance patterns in an 'engagement' program focussed on arts and lifestyle activities (n = 95), and a routine service dataset collected from seven years of therapeutic intervention (n = 3,893), measuring substance dependence (SDS), psychological distress (K10) and quality of life (EQoL).ResultsAnalysis reveals that young people were retained in the program at high proportion (63% at six months) and more than half of these returned at a frequency of weekly or more often. Young people participating in the therapeutic component of the program reported significant improvements in all key wellbeing indicators with SDS, K10 and EQoL scores significantly improving (at p < .001). These improvements occurred rapidly, within the first 30 days, and were maintained over the 90 day study period. Moreover, young people with the highest SDS and K10 scores and lowest quality of life at baseline experienced the most positive changes.ConclusionAligning engagement program with therapeutic intervention can provide comprehensive support to disadvantaged young people, producing substantial improvements in AOD use, distress and wellbeing.

Abstract Background Amelogenesis imperfecta (AI) is a type of hereditary diseases that manifest defects in the formation or mineralization of enamel. Recently, it is reported that inactivation of FAM20C, a well-known Golgi casein kinase, caused AI. However, the mechanism of it is still unknown. The aim of this study was to explore the molecular mechanism of AI, which caused by ablation of FAM20C. Results In the Sox2-Cre;Fam20C fl/fl (cKO) mouse, we found abnormal differentiation of ameloblasts, improper formation and mineralization of enamel, and downregulation of both mRNA and protein level of enamel matrix proteins, including amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM). The levels of BMP2, BMP4 and BMP7, the ligands of BMP signaling pathway, and phosphorylation of Smad1/5/8, the key regulators of BMP signaling pathway, were all decreased in the enamel matrix and the ameloblast of the cKO mice, respectively. The expression of cyclin-dependent kinase inhibitor (P21), muscle segment homeobox genes 2 (Msx2), which are the target genes of the BMP signaling pathway, and laminin 3, the downstream factor of Msx2, were all significantly decreased in the ameloblasts of the cKO mice compared to the control mice. Conclusion the results of our study suggest that ablation of FAM20C leads to AI through inhibiting the Smad dependent BMP signaling pathway in the process of amelogenesis.

Sweet potato virus disease (SPVD) is one of the main virus diseases in sweet potato [Ipomoea batatas (L.) Lam] that seriously affects the yield of sweet potato. Therefore, the establishment of a simple, rapid and effective method to detect SPVD is of great significance for the early warning and prevention of this disease. In this study, the experiment was carried out in two years to compare the grafting method and side grafting method for three sweet potato varieties, and the optimal grafting method was selected. After grafting with seedlings infected with SPVD, the symptomatic diagnosis and serological detection were performed in 86 host varieties, and the differences in SPVD resistance were determined by fluorescence quantitative PCR (qRT-PCR) and nitrocellulose membrane enzyme-linked immunosorbent assay (NCM-ELISA). The results showed that the survival rate of grafting by insertion method was significantly higher than that by side grafting method, and the disease resistance of different varieties to sweet potato virus disease was tested. The detection method established in this study can provide theoretical basis for identification and screening of resistant sweet potato varieties.

Introduction More research and policy action are needed to improve migrant health in areas such as sexual health and blood-borne viruses (SHBBV). While Knowledge, Attitudes and Practice Surveys (KAPS) can inform planning, there are no SHBBV KAPS suitable for use across culturally and linguistically diverse contexts. This study pretests one instrument among people born in Sub-Saharan Africa, South-East and North-East Asia living in Australia.Methods Employees of multicultural organisations were trained to collect data over three rounds using a hybrid qualitative pretesting method. Two researchers independently coded data. Researchers made revisions to survey items after each round. Responses to feedback questions in the final survey were analysed.Results Sixty-two participants pretested the survey. Issues were identified in all three rounds of pretesting. Of the 77 final survey respondents who responded to a survey experience question, 21% agreed and 3% strongly agreed with the statement ‘I found it hard to understand some questions/words’.Conclusion It is essential to pretest SHBBV surveys in migrant contexts. We offer the following pretesting guidance: (1) large samples are needed in heterogeneous populations; (2) intersectionality must be considered; (3) it may be necessary to pretest English language surveys in the participants’ first language; (4) bilingual/bicultural workers must be adequately trained to collect data; (5) results need to be interpreted in the context of other factors, including ethics and research aims; and (6) pretesting should occur over multiple rounds.

BackgroundMigrants are underrepresented in population health surveys. Offering translated survey instruments has been shown to increase migrant representation. While 'team translation' represents current best practice, there are relatively few published examples describing how it has been implemented. The purpose of this paper is to document the process, results and lessons from a project to translate an English-language sexual health and blood-borne virus survey into Khmer, Karen, Vietnamese and Traditional Chinese.MethodsThe approach to translation was based on the TRAPD (Translation, Review, Adjudication, Pretesting, and Documentation) model. The English-language survey was sent to two accredited, independent translators. At least one bilingual person was chosen to review and compare the translations and preferred translations were selected through consensus. Agreed translations were pretested with small samples of individuals fluent in the survey language and further revisions made.ResultsOf the 51 survey questions, only nine resulted in identical independent translations in at least one language. Material differences between the translations related to: (1) the translation of technical terms and medical terminology (e.g. HIV); (2) variations in dialect; and (3) differences in cultural understandings of survey concepts (e.g. committed relationships).ConclusionSurvey translation is time-consuming and costly and, as a result, deviations from TRAPD 'best practice' occurred. It is not possible to determine whether closer adherence to TRAPD 'best practice' would have improved the quality of the resulting translations. However, our study does demonstrate that even adaptations of the TRAPD method can identify issues that may not have been apparent had non-team-based or single-round translation approaches been adopted. Given the dearth of clear empirical evidence about the most accurate and feasible method of undertaking translations, we encourage future researchers to follow our example of making translation data publicly available to enhance transparency and enable critical appraisal.

Abstract 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.

Abstract 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.

IntroductionWe 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.MethodsPoisson 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.ResultsBetween 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, pConclusionThe epidemiology of HIV in Australia is changing, with an increase in HIV diagnosis rates attributed to male-to-male sex amongst men born in Asia and the Americas. Tailored strategies must be developed to increase access to, and uptake of, prevention, testing and treatment in this group.

Abstract Objective: To examine the validity and impact of record linkage using name code compared to full name records. Methods: A registry of 45,419 opioid substitution clients (1985–2007) was linked with national population‐based death and cancer registries using registrant's name, date of birth, sex, state, postcode and date of death. Records were linked using full name and then using the first two letters of the given and surname (2×2 name code). Sensitivity and specificity were computed and regression analysis used to identify factors related to linkage accuracy. Standardised mortality ratios (SMR) and standardised cancer incidence ratios (SIR) were estimated. Results: The sensitivity and specificity of name code compared to full name linkage were 65.31% and 99.91% for death records and 76.81% and 99.89% for cancer records. Registrants' age and sex and accuracy of the registries were associated with risk of false linkages. Death and cancer risks (SMR 6.98, 95%CI 6.77–7.19; SIR 1.16, 95%CI 1.08–1.24) were significantly under‐estimated using name code linkage (SMR 4.39, 95%CI 4.23–4.56; SIR 0.92, 95%CI 0.85–0.99). Conclusion: Record linkage using 2×2 name code has low sensitivity but high specificity, resulting in conservative estimates of death and cancer risk. This may translate to meaningful differences in outcomes.

BACKGROUND:Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. METHODS:Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression. RESULTS:We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2-6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2-4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5-7.3], p = 0.004), reaching the "Medicare safety net" (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1-4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0-6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0-18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1-5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3-7.0], p = 0.012). CONCLUSIONS:In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an undetectable viral load. Associations were with social/economic/cultural/patient engagement factors, but not ART regimen/clinical factors. These associations may help identify those at higher risk of future virological failure and guide patient education and support.

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

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 p<0.01). In poly-drug users, who injected drugs two times per day was associated with the highest proportion of people who engaged in sex and commercial sex (p<0.05). For SD-only users, increased drug use was not associated with reducing sexual risk (p>0.05). 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. [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]

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: Mobile phone apps are now the most popular method that Australian gay men use to find sex partners. Partner-seeking mobile phone apps use location functions to identify like-minded men and display their proximity. This study examines whether meeting partners via mobile apps is associated with a greater risk of HIV and sexually transmitted infections (STIs) than with other ways of meeting partners.Methods: Data were analysed from the Gay Community Periodic Surveys, community-based, cross-sectional surveys conducted in Australian state capital cities between 2010 and 2014. χ2 tests and multinomial logistic regression were used to analyse differences in risk profiles of men who used different methods to meet partners.Results: Data were analysed from 36 428 men who participated in the Gay Community Periodic Surveys between 2010 and 2014. In 2014, 4116 men reported meeting sex partners with the use of mobile apps, increasing from 23.9% in 2011 to 42.5% in 2014. Men who used a combination of online and offline methods reported a greater number of sex partners and were more likely to report a recent STI than men who used online methods only or offline methods only.Conclusions: There has been a steep increase in the use of mobile phone apps by gay men in Australia to meet male partners. However, men who use a combination of mobile phone apps, internet websites and offline places to meet partners appear to be at increased risk of STIs or HIV compared with men who use a narrower range of online and offline methods. [ABSTRACT FROM AUTHOR]

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]

Background: To date, limited research has been conducted to identify the personal and contextual factors that contribute to women's entry into the sex industry in China.Methods: The reasons for and factors associated with voluntary entry into the sex industry were explored through in-depth interviews conducted with 38 Chinese women who were held in detention centres for selling sex.Results: Women's personal accounts reveal that entry into sex work is influenced by life aspirations, family responsibilities and social connections, which facilitate mobility to a new urban environment in which they encounter opportunities and challenges. Findings highlight the complex interactions between individual and contextual factors in relation to women's entry into sex work.Conclusions: In a rapidly developing country such as China, entry into sex work may appeal to women of low socioeconomic status, particularly young women who have recently migrated to urban areas. For members of this mobile and relatively disadvantaged population, comprehensive social services and support are urgently needed. [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 article discusses a study which presents findings from the Gay Community Periodic Surveys from 2007 and 2001 and compares sexual risk practices, drug use and HIV prevalence between Indigenous and Anglo-Australian men having sex with men (MSM). Several studies have reported a higher prevalence of illicit drug use among MSM as compared with heterosexual men citing an analysis by C. G.Lawrence et al which suggests that Indigenous Australian MSM may be higher rates of drug use compared with their nonIndigenous peers. Findings showed significantly higher levels of intercourse with casual male partners (UAIC) and injecting drug use (IDU) among Indigenous men.

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]

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]

In recent years, increases in both risk behavior and in seroconversion among homosexually active men have been noted in a number of parts of the world. Data were available from 903 HIV negative homosexual men regarding number of acts of unprotected anal intercourse (UAI), separated into receptive and insertive UAI, with and without ejaculation, with steady and with casual partners. Partners were classified according to serostatus as reported by respondents. Men ( N = 325) reported 13,692 UAI acts, most of which were with steady partners, of whom most were reported to be HIV-negative. With HIV-positive partners, both steady and casual, and with casual partners of unknown serostatus, receptive UAI with ejaculation was relatively rare. Insertive UAI without ejaculation was relatively common with casual partners of unknown serostatus. Patterns of UAI suggest that risk of transmission may be greater with steady partners. Men appear to modify practice according to both the nature of the relationship (steady or casual) and (assumed) serostatus of partner. [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]

This study aimed to determine and describe HIV-negative gay men's willingness to participate in HIV vaccine trials. Data were from participants who completed face-to-face interviews during the first 18 months (to the end of 2002) of recruitment into the Health in Men cohort of HIV-negative gay men in Sydney. A key outcome measure was a scale of Willingness to Participate in HIV Vaccine Trials, with scores ranging from 1 (unwilling) to 4 (willing). The 903 participants ranged in age from 18 to 75years (median=36). Mean of Willingness to Participate in HIV Vaccine Trials was 2.53 (standard deviation=0.54), with approximately 51% of the men having a score greater than the midpoint of 2.50. A reduced linear regression model yielded four significant independent associations with Willingness to Participate in HIV Vaccine Trials: lack of tertiary education (P <0.001),having engaged 'in the previous six months' in any unprotected anal intercourse with casual or non-concordant regular partners (P <0.001), higher self-rated likelihood of HIV infection (P <0.01), and higher mean scores on a scale of Comfort with Participation in HIV VaccineTrials (P <0.001). The willingness of HIV-negative gay men at potentially higher risk for HIV to participate in HIV vaccine trials augurs well for enrolment in HIV vaccine efficacy trials. Recruitment into trials is likely to be enhanced by addressing salient concerns such as confidentiality and vaccine-induced antibody positivity. Also, it will be important to ensure that gay men are educated and fully informed about HIV vaccines and trial processes. [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]