Changing attitudes about LGBTQ+ older adults: the Gen Silent Survey Project.

OBJECTIVES: Lesbian, gay, bisexual, transgender, queer, and more (LGBTQ+) older adults may experience challenges accessing services due to stigma. Aging service providers seeking to create an inclusive culture need training tools. This study examined if a film (Gen Silent) could increase provider's knowledge of and empathy for LGBTQ+ older adults. METHODS: A pretest - posttest survey was administered at film screenings in New Hampshire to assess knowledge and attitudes of participants (N = 108). Data were analyzed descriptively, Wilcoxon signed-rank test was used to compare matched samples, and linear and logistic regression models compared group differences. RESULTS: Scores on eight of the nine measures improved after watching Gen Silent. Most participants (83%) indicated their thoughts and views had changed after watching the film. Statistically significant between group differences are discussed. CONCLUSIONS: The documentary Gen Silent was found to be an adequate, introductory training tool about LGBTQ+ aging.

HIV Stigma and Older Men's Psychological Well-Being: Do Coping Resources Differ for Gay/Bisexual and Straight Men?

OBJECTIVES: This study investigated whether sexual orientation moderated the mediation effects of coping resources (i.e., spirituality and complementary and integrative health [CIH] use) in the relationship between HIV stigma and psychological well-being (PWB) among older men with HIV (MWH). METHOD: Data from the Research of Older Adults with HIV (ROAH) study was used (N = 640, Age 50+). Structural equation modeling (SEM) was employed to examine a coping resource mediation model. We used a multiple-group procedure to test moderation effects by sexual orientation. RESULTS: HIV stigma was negatively associated with spirituality and PWB. HIV stigma accounted for a significant amount of variance in PWB, with significant indirect effects via spirituality, indicating a partial mediation. Chi-square difference tests supported the hypothesis that this mediation effect was moderated by sexual orientation. CIH use was not statistically significant. DISCUSSION: HIV stigma's negative relationship with PWB was salient in both groups. Spirituality's buffer between HIV stigma and PWB was stronger in older gay/bisexual MWH compared to their heterosexual counterparts. With respect to HIV stigma, older gay/bisexual MWH exhibited a "crisis competence" in coping with stigma, perhaps through overcoming past homophobia related to their sexual minority status (i.e., homophobia).

Pyrin-only protein 2 limits inflammation but improves protection against bacteria.

Pyrin domain-only proteins (POPs) are recently evolved, primate-specific proteins demonstrated in vitro as negative regulators of inflammatory responses. However, their in vivo function is not understood. Of the four known POPs, only POP2 is reported to regulate NF-κB-dependent transcription and multiple inflammasomes. Here we use a transgenic mouse-expressing POP2 controlled by its endogenous human promotor to study the immunological functions of POP2. Despite having significantly reduced inflammatory cytokine responses to LPS and bacterial infection, POP2 transgenic mice are more resistant to bacterial infection than wild-type mice. In a pulmonary tularaemia model, POP2 enhances IFN-γ production, modulates neutrophil numbers, improves macrophage functions, increases bacterial control and diminishes lung pathology. Thus, unlike other POPs thought to diminish innate protection, POP2 reduces detrimental inflammation while preserving and enhancing protective immunity. Our findings suggest that POP2 acts as a high-order regulator balancing cellular function and inflammation with broad implications for inflammation-associated diseases and therapeutic intervention.

Stigma and Psychological Well-being Among Older Adults With HIV: The Impact of Spirituality and Integrative Health Approaches.

Purpose of the Study: The National Institutes of Health calls for research that explores what it means to age optimally with HIV/AIDS as half of the U.S. people with HIV are aged 50 or older. This study applied the stress process model to examine the association between HIV stigma and psychological well-being and mediating resources (i.e., spirituality and complementary and integrative health [CIH]) approaches) in older adults with HIV. Design and Methods: Using data from the Research on Older Adults with HIV (ROAH) study, structural equation modeling was used to estimate these relationships within a latent variable model. Namely, a direct negative association between HIV stigma and psychological well-being was hypothesized that would be mediated by spirituality and/or CIH use. Results: The analyses showed that the model fits the data well [χ2 (137, N = 914) = 561.44, p = .000; comparative fit index = .964; root mean square error of approximation = .058, 95% confidence interval = .053 to .063]. All observed variables significantly loaded on their latent factor, and all paths were significant. Results indicated that spirituality and CIH use significantly mediated the negative association between HIV stigma and psychological well-being. Implications: Findings highlight the importance of spiritual and CIH interventions for older adults with HIV/AIDS. Practice recommendations are provided at the micro- and mesolevel.

Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility.

Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerability-for example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic.

Social Network and Nutritional Value of Congregate Meal Programs: Differences by Sexual Orientation.

This study explored the associations between sexual orientation and the perceived social network and nutritional value of congregate meal programs (CMPs) in Massachusetts (N = 289). Descriptives, t tests, and chi-square tests analyzed sexual orientation differences. Linear regression tested the effects of sexual orientation on the value of CMPs. Sexual minorities (SMs) were more likely to have non-kin-based social networks and reported higher levels of loneliness compared with heterosexuals. Heterosexuals, fewer of whom have non-kin-based networks, place a stronger value on access to a social network via CMPs. Nutritional value is important for people of all sexual orientations. SMs traveled seven times the distance to attend CMPs, highlighting the need for greater access to such sites. Results of this study support the specification of SMs as a population of "greatest social need" under the Older Americans Act and the expansion of services that are tailored for their social support needs.

Providing Competent and Affirming Services for Transgender and Gender Nonconforming Older Adults.

Despite the growing visibility and acceptance of transgender and gender nonconforming (TGNC) individuals, TGNC older adults experience many barriers in accessing competent and affirming health and social services due to anti-TGNC prejudice, discrimination, and lack of competent healthcare training on the part of healthcare workers. Clinical gerontologists and geriatricians will likely encounter TGNC adults in their practice given population aging and greater numbers of TGNC people who are living in their affirmed gender identities. The American Psychological Association recently published its Guidelines for Psychological Practice with Transgender and Gender Nonconforming People, which document the unique needs of TGNC individuals and outlines approaches for competent and affirming service provision (APA, 2015). We interpret these Guidelines using a gerontological lens to elucidate specific issues faced by the TGNC older adult along with the practice and policy implications for this population.

A State-Level Review of Diversity Initiatives in Congregate Meal Programs Established Under the Older Americans Act.

The Older Americans Act (OAA) congregate meal program (CMP) targets those most at risk for nutritional deficiencies, social isolation, and institutionalization. Social minorities (racial, ethnic, cultural, and sexual minorities) are at high risk for all three. This study explores state-level diversity initiatives to welcome these social minorities in CMPs. A national survey was distributed to each State Unit on Aging, all but three states participated. The majority of states (64.6%) target CMPs to a specific racial, ethnic, or cultural minority; five states target sexual minorities (lesbian, gay, bisexual, and transgender [LGBT]). Negative binomial regression results find state minority population percentage is a significant predictor of the number of diversity initiatives at CMPs. States with LGBT CMPs reported the highest levels of racial/ethnic/cultural diversity initiatives and high levels of statewide LGBT protective policies. Recommendations are suggested that build upon the diversification success of states to further the mission of OAA in reaching high-risk older adults.

Substance use and sexual risk differences among older bisexual and gay men with HIV.

Bisexual and gay men are disproportionately affected by HIV/AIDS. Research typically combines these groups into the category of men who have sex with men, and little is known about between-group differences. HIV-positive populations are aging and have high rates of substance use compared to non-infected peers, while substance use among older adults has increased and is associated with unprotected intercourse. Among a sample of 239 HIV-positive bisexual and gay men aged 50 and older, bisexual men were more likely to report cigarette, cocaine, crack, and heroin use compared with gay men. However, bisexual men were less likely to use crystal meth, club drugs, poppers (nitrate inhalers), and erectile dysfunction (ED) medications compared to gay men. While bisexual men reported lower rates of unprotected sex, logistic regression analysis found that current use of poppers and ED drugs, which were higher among gay men, explained this difference. Implications for education and prevention programs are discussed.

Do LGBT aging trainings effectuate positive change in mainstream elder service providers?

This study aims to provide empirical evidence regarding whether attitudes, beliefs, and intentions of elder-service providers can be positively affected as a result of attending cultural competency training on the unique challenges of sexual and gender minorities. Stigmatization throughout the lifespan may have a causal influence on barriers to care, social isolation, and concomitant health disparities. Data were collected for this study at 4 Massachusetts training events to pilot a cultural competency workshop on lesbian, gay, bisexual, and transgender (LGBT) aging for mainstream elder service providers. This quasi-experimental study included the analysis of pre- and posttest surveys completed by the service-provider attendees (N = 76). The analytic strategy included descriptive statistics, paired t tests, chi-square analyses, and repeated measures analyses of variance. Findings revealed statistically significant improvement in numerous aspects of providers' knowledge, attitudes, and behavioral intentions subsequent to the training sessions. These included (p = .000) awareness of LGBT resources, policy disparities, spousal benefits for same-sex couples, and the intention to challenge homophobic remarks. This study concludes that mainstream elder-service provider training on LGBT aging issues results in positive change. Recommendations include long-term follow up of participants, the inception of agency-level surveys to appraise institutional culture change, and increased curriculum on transgender older adults.

"Chemo brain"--is cancer survivorship related to later-life cognition? Findings from the health and retirement study.

OBJECTIVE: Studies have shown a correlation between cancer and cognition referred to as "chemo brain." This study investigated the relationship between cancer and later-life cognition using nationally representative data. METHOD: Analysis of the 2006 Health and Retirement Study investigated the (a) effects of cancer survivorship on the total cognition score using linear regression in adults age 65+ (n = 9,814) and (b) the effects of cancer treatment on the total recall index using linear regression in adults age 50+ (n = 657). RESULTS: Total cognition score is not associated with cancer survivorship. The association between long-term cancer survivorship and cognition score was significant (p < .05; b = .276). Total recall index is not associated with chemotherapy. DISCUSSION: These results support other research suggesting that chemo brain may be biased by expectation as well as favored by research that relies upon self-reported cognitive measures versus cognitive testing. The study was limited by the cross-sectional design.

Multiple mechanisms mediate enhanced immunity generated by mAb-inactivated F. tularensis immunogen.

We have previously demonstrated that immunization with the inactivated Francisella tularensis, a Category A intracellular mucosal pathogen, combined with IgG2a anti-F. tularensis monoclonal antibody (Ab), enhances protection against subsequent F. tularensis challenge. To understand the mechanism(s) involved, we examined the binding, internalization, presentation, and in vivo trafficking of inactivated F. tularensis in the presence and absence of opsonizing monoclonal Ab. We found that when inactivated F. tularensis is combined with anti-F. tularensis monoclonal Ab, presentation to F. tularensis-specific T cells is enhanced. This enhancement is Fc receptor (FcR)-dependent, and requires a physical linkage between the monoclonal Ab and the inactivated F. tularensis immunogen. This enhanced presentation is due, in part, to enhanced binding and internalization of inactivated F. tularensis by antigen(Ag)-presenting cells, and involves interactions with multiple FcR types. Furthermore, targeting inactivated F. tularensis to FcRs enhances dendritic cell maturation and extends the time period over which Ag-presenting cells stimulate T cells. In vivo trafficking studies reveal enhanced transport of inactivated F. tularensis immunogen to the nasal-associated lymphoid tissue in the presence of monoclonal Ab, which is FcRn-dependent. In summary, these are the first comprehensive studies using a single-vaccine protection model/immunogen to establish the array of mechanisms involved in enhanced immunity/protection mediated by an FcR-targeted mucosal immunogen. These results demonstrate that multiple cellular/immune mechanisms contribute to FcR-enhanced immunity.

CIITA enhances HIV-1 attachment to CD4+ T cells leading to enhanced infection and cell depletion.

Activated CD4(+) T cells are more susceptible to HIV infection than resting T cells; the reason for this remains unresolved. Induction of CIITA and subsequent expression of the MHC class II isotype HLA-DR are hallmarks of CD4(+) T cell activation; therefore, we investigated the role of CIITA expression in T cells during HIV infection. CIITA-expressing SupT1 cells display enhanced virion attachment in a gp160/CD4-dependent manner, which results in increased HIV infection, virus release, and T cell depletion. Although increased attachment and infection of T cells correlated with HLA-DR surface expression, Ab blocking, transient expression of HLA-DR without CIITA, and short hairpin RNA knockdown demonstrate that HLA-DR does not directly enhance susceptibility of CIITA-expressing cells to HIV infection. Further analysis of the remaining MHC class II isotypes, HLA-DP and HLA-DQ, MHC class I isotypes, HLA-A, HLA-B, and HLA-C, and the class II Ag presentation genes, invariant chain and HLA-DM, demonstrate that these proteins likely do not contribute to CIITA enhancement of HIV infection. Finally, we demonstrate that in activated primary CD4(+) T cells as HLA-DR/CIITA expression increases there is a corresponding increase in virion attachment. Overall, this work suggests that induction of CIITA expression upon CD4(+) T cell activation contributes to enhanced attachment, infection, virus release, and cell death through an undefined CIITA transcription product that may serve as a new antiviral target.

Class II transactivator (CIITA) enhances cytoplasmic processing of HIV-1 Pr55Gag.

BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.

Transforming signals resulting from sustained activation of the PDGFbeta receptor in mortal human fibroblasts.

The platelet-derived growth factor beta receptor (PDGFbetaR) plays an important role in proliferation and motility of fibroblasts. We have been investigating the effects of sustained PDGFbetaR activation in mortal human diploid fibroblasts (HDFs), which are typically difficult to transform. We have previously shown that the bovine papillomavirus E5 protein, through its ability to crosslink and constitutively activate the PDGFbetaR, induces morphological transformation, enhanced growth and loss of contact inhibition (focus formation) in HDFs. Here, we characterized two E5 mutants as being severely defective for focus formation but still competent for enhanced growth, suggesting that proliferation is insufficient for loss of contact inhibition. These E5 mutants were then used in a comparative study to distinguish the PDGFbetaR signaling intermediates required for the enhanced growth phenotype from those required for focus formation. Our data suggested that a PI 3-kinase (PI3K)-AKT-cyclin D3 pathway, a Grb2-Gab1-SHP2 complex and JNK played a role in the enhanced growth phenotype. However, a SHP2-p66Shc-p190BRhoGAP complex and ROCK were implicated exclusively in focus formation. We speculate that a SHP2-p66Shc-p190BRhoGAP signaling complex recruited to the activated PDGFbetaR promotes a distinct Rho-dependent process required for focus formation but not growth of HDFs.

Evidence that accumulation of mutants in a biofilm reflects natural selection rather than stress-induced adaptive mutation.

The accumulation of mutant genotypes within a biofilm evokes the controversy over whether the biofilm environment induces adaptive mutation or whether the accumulation can be explained by natural selection. A comparison of the virulence of two strains of the dental pathogen Streptococcus mutans showed that rats infected with one of the strains accumulated a high proportion (average, 22%) of organisms that had undergone a deletion between two contiguous and highly homologous genes. To determine if the accumulation of deletion mutants was due to selection or to an increased mutation rate, accumulations of deletion mutants within in vitro planktonic and biofilm cultures and within rats inoculated with various proportions of deletion organisms were quantified. We report here that natural selection was the primary force behind the accumulation of the deletion mutants.

Functional analysis of glucan binding protein B from Streptococcus mutans.

Mutans streptococci are major etiological agents of dental caries, and several of their secreted products contribute to bacterial accumulation on teeth. Of these, Streptococcus mutans glucan binding protein B (GbpB) is a novel, immunologically dominant protein. Its biological function is unclear, although GbpB shares homology with a putative peptidoglycan hydrolase from S. agalactiae and S. pneumoniae, indicative of a role in murein biosynthesis. To determine the cellular function of GbpB, we used several approaches to inactivate the gene, analyze its expression, and identify interacting proteins. None of the transformants analyzed were true gbpB mutants, since they all contained both disrupted and wild-type gene copies, and expression of functional GbpB was always conserved. Thus, the inability to obtain viable gbpB null mutants supports the notion that gbpB is an essential gene. Northern blot and real-time PCR analyses suggested that induction of gbpB expression in response to stress was a strain-dependent phenomenon. Proteins that interacted with GbpB were identified in pull-down and coimmunoprecipitation assays, and these data suggest that GbpB interacts with ribosomal protein L7/L12, possibly as part of a protein complex involved in peptidoglycan synthesis and cell division.

Price elasticities for three types of CAM services: Experiences of a Boston Public Health Clinic.

OBJECTIVES: This paper addresses price elasticity, an indicator for the responsiveness of demand for healthcare to changes in price, in the context of a large public health clinic that provides acupuncture, Chinese herbal medicine, and shiatsu. DESIGN: The study is descriptive and observational. The observations resulted from a "natural experiment" and involved examining utilization before and after a 5 dollars(17%) price increase for all services. Aggregate data were collected on demographics and utilization of 222 clients using services over a 6-month period in 2004. SETTING: Pathways to Wellness is a nonprofit agency that provides complementary and alternative medicine (CAM) services to underserved, low-income clients. The agency administers a clinic that has been operating for the past 15 years and currently provides approximately 1200 treatments per month. OUTCOME MEASURES: Utilization data on number of treatments administered were collected for 3 months prior to the price increase and compared to utilization data for the 3 months after the price increase. Comparisons were made for both the immediate changes in utilization (2-month data) and quarterly changes in utilization (6-month data). RESULTS: Utilization dropped for all three services in the month after the price increase. Values of elasticity associated with the immediate changes were calculated as -0.35 for acupuncture services, -1.31 for Chinese herbal consultations, and -2.34 for shiatsu services, and indicate a wide range of responsiveness. CONCLUSIONS: Values of price elasticities indicate a range of differential responses to change in price for services. The relatively smaller drop in utilization of acupuncture services may be consistent with clients' perceptions of effectiveness or immediacy of treatment symptom relief.