Oncolytic α-herpesvirus and myeloid-tropic cytomegalovirus cooperatively enhance systemic antitumor responses.

Oncolytic virotherapy aims to activate host antitumor immunity. In responsive tumors, intratumorally injected herpes simplex viruses (HSVs) have been shown to lyse tumor cells, resulting in local inflammation, enhanced tumor antigen presentation, and boosting of antitumor cytotoxic lymphocytes. In contrast to HSV, cytomegalovirus (CMV) is nonlytic and reprograms infected myeloid cells, limiting their antigen-presenting functions and protecting them from recognition by natural killer (NK) cells. Here, we show that when co-injected into mouse tumors with an oncolytic HSV, mouse CMV (mCMV) preferentially targeted tumor-associated myeloid cells, promoted the local release of proinflammatory cytokines, and enhanced systemic antitumor immune responses, leading to superior control of both injected and distant contralateral tumors. Deletion of mCMV genes m06, which degrades major histocompatibility complex class I (MHC class I), or m144, a viral MHC class I homolog that inhibits NK activation, was shown to diminish the antitumor activity of the HSV/mCMV combination. However, an mCMV recombinant lacking the m04 gene, which escorts MHC class I to the cell surface, showed superior HSV adjuvanticity. CMV is a potentially promising agent with which to reshape and enhance antitumor immune responses following oncolytic HSV therapy.

A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease.

PURPOSE: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution. DESIGN: Retrospective, single-institution cohort review. PARTICIPANTS: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. METHODS: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects. MAIN OUTCOME MEASURES: Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field. RESULTS: A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4-76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual. CONCLUSIONS: ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Physical durability: are bed nets getting any stronger?

BACKGROUND: For at least a decade, concerns have been raised about the physical durability of insecticide-treated nets (ITNs) and their ability to remain in good condition for at least three years. To discover if the resistance to damage (RD) of ITNs has improved or not, the RD scores of ITNs sampled in 2013 and 2020 were compared. METHODS: The RD scores and disaggregated textile performance data for nine ITNs recommended by the WHO pesticide evaluation scheme (WHOPES) measured in 2013 were compared with WHO-prequalified ITNs sampled in 2020. This included assessment of newer ITNs not available in 2013, to determine the extent to which product development has led to performance improvements across all available ITNs in the intervening years. RESULTS: The resistance to damage of ITNs has not generally improved from 2013 to 2020, and in some cases performance is worse. The average RD score of comparable ITNs brands decreased from 40 in 2013 to 36 in 2020. Of the nets available in 2020, only two of the twenty-four ITN products tested achieved an RD score of > 50, while six ITNs had very low RD scores of < 30, highlighting a serious inherent, and literal weakness in many WHO-prequalified ITNs. CONCLUSIONS: The long-term physical durability of ITN products cannot be expected to improve while their resistance to damage remains so low, and major upgrades to the performance standards of textile materials used to make ITNs, as well as incentives to develop stronger ones are urgently required.

Smoking cessation among sexual minority women: Differences in cigarette quit ratios across age, race/ethnicity, and sexual orientation.

OBJECTIVE: Sexual minority (SM) women experience tobacco-related disparities and report a higher prevalence of cigarette use, as well as subgroup differences in use, but little is known about their quitting behavior. This study used data from a national sample of United States SM women to examine cigarette quit ratios overall and by age, race/ethnicity, and sexual orientation. METHODS: Using baseline survey data from the Generations Study (2016-2017, N = 812), we calculated quit ratios among SM women reporting lifetime smoking (100+ cigarettes) who reported currently smoking "not at all" relative to those reporting smoking "every day or some days." Quitting was compared across cohort, race/ethnicity, and sexual orientation, controlling for household income. RESULTS: SM women reporting lifetime smoking in the older cohort were significantly more likely to report quitting than those in the younger cohort. Bisexual women also reported a greater likelihood of quitting than gay/lesbian women. There was no association between race/ethnicity and the probability of quitting smoking. CONCLUSIONS: SM women remain a priority for tobacco prevention and cessation efforts. There is evidence that the probability of quitting cigarettes differs across sexual orientation and age cohorts, which has implications for tailoring of interventions and tobacco communications.

MENISCUS MICROPYON: An Ophthalmoscopic Sign Possibly Associated With Epiretinal Proliferation After Retinal Surgery With Gas Tamponade.

PURPOSE: To describe an ophthalmoscopic sign, termed a meniscus micropyon, and its possible association with proliferative vitreoretinopathy/epiretinal membrane (ERM) formation after retinal surgery with gas tamponade. METHODS: Patients with intravitreal gas were examined postoperatively by one of six vitreoretinal surgeons from four institutions. A micropyon was defined as a white-yellow, solid-appearing consolidation along the meniscus (i.e., the fluid-gas interface). RESULTS: A micropyon was visualized and photographed in 49 patients who received intravitreal gas. Preoperatively, retinal breaks were present in all 49 eyes and rhegmatogenous retinal detachment in 45 (92%). Postoperatively, 39 eyes (80%) developed epiretinal proliferation: 16 eyes (33%) developed recurrent rhegmatogenous retinal detachment from proliferative vitreoretinopathy, 6 eyes (12%) re-detached without frank proliferative vitreoretinopathy, 9 eyes (18%) developed postoperative ERM/worsening, and 8 eyes (16%) had postoperative ERM but no preoperative optical coherence tomography to determine if the postoperative ERM was new or worsening. The single-operation anatomical success in eyes with a micropyon was 51%, which was lower than that of a contemporaneous rhegmatogenous retinal detachment control group (91%) in which no micropyon was detected. In two patients, micropyons were biopsied during pars plana vitrectomy and examined histopathologically; they consist predominantly of white blood cells. CONCLUSION: The meniscus micropyon is an ophthalmoscopic sign that can occur after retinal surgery with gas tamponade. Features that distinguish a micropyon from postvitrectomy fibrin/fibrinoid syndrome include delayed appearance, hyperautofluorescence, absence of translucent strands or sheets in the anterior chamber or vitreous cavity, and the histopathologic identification of white blood cells. A clinically detectable micropyon may be a biomarker of proliferative vitreoretinopathy/ERM formation.

Geographical Variation in the Associations Between School Characteristics and Homophobic Bullying: a Contextual Analysis.

Homophobic bullying constitutes a serious threat to adolescent well-being and could be understood as an ecological phenomenon, influenced by diverse school, regional, and community contexts. This study examined geographic variations in the relationship between school characteristics and homophobic bullying. Data from 2244 California schools, including student surveys and administrative records, were combined and analyzed using geographically weighted regression (GWR). Results showed that the associations between school characteristics and general victimization were consistent across geographic areas. However, when it came to homophobic bullying, the relationships with school characteristics varied significantly based on location. Notably, regions with high intolerance, urbanity, large school size, and small student-teacher ratios appeared to offer protection against bullying. Additionally, student socioeconomic status influenced bullying in disadvantaged rural schools with limited Gay-Straight Alliance (GSA) presence. Ethnic diversity also played a role, with low diversity or dominance of two ethnic groups linked to higher bullying rates.

Revisiting the Latin vocabulary of Terminologia Histologica: I. Nouns.

Almost 20% of the Latin nouns (193/993) in Terminologia Histologica (TH), the international standard nomenclature for human histology and cytology, display linguistic problems, particularly in the areas of orthography, gender, and declension. Some anatomists have opposed efforts to restore the quality of the Latin nomenclature as pedantry, preferring to create or modify Latin words so that they resemble words in English and other modern languages. A Latin microanatomical nomenclature is vulnerable to the criticism of anachronism, so the requirement for the use of authentic Latin, including derivation of new words from Greek and Latin words rather than from modern languages, if possible, may be even greater than it is for the anatomical nomenclature. The most common problem identified here appears to have been caused by derivation of Latin nouns by addition of -us and -um second declension endings to English words. Many Latin nouns (128) in TH contain one of six morphemes that have been treated this way even though the original Greek words are either first declension masculine or third declension neuter nouns. Ironically, deriving Latin nouns directly from Greek morphemes often results in words that look more familiar to speakers of Romance and Germanic languages than those derived indirectly through modern languages (e.g., astrocyte, collagene, dendrita, lipochroma, osteoclasta and telomere instead of astrocytus, collagenum, dendritum, lipochromum, osteoclastus, and telomerus).

The Developmental Collision Hypothesis: An Empirical Test With Three Generations of Sexual Minority Youth.

Sexual minority youth experience disproportionate rates of mental health symptomatology relative to their heterosexual peers. Less is known about why these disparities have persisted despite growing public awareness of sexual diversity. The developmental collision hypothesis states that increased cultural visibility of sexual diversity has accelerated the developmental timing of sexual minority identity formation processes such that they collide with early adolescence, a uniquely sensitive period for experiencing identity-based stigma and associated mental health vulnerability. To test this hypothesis, levels and relations between ages of sexual minority identity development milestones, frequency of LGBT-related victimization, and depressive symptoms were examined across three age-matched but cohort-distinct samples of sexual minority adolescents. Data come from three secondary datasets of sexual minority youth who were adolescents in the 1990s, 2000s, and 2010s, respectively: the Challenges and Coping Study, the Victimization and Mental Health among High Risk Youths Study, and the Risk and Protective Factors for Suicide among Sexual Minority Youth Study (n = 1312; Mage = 17.34, SD = 1.30; 52% female). Adolescents from more recent cohorts reported earlier mean ages of several milestones but similar frequencies of LGBT-related victimization relative to those from less recent cohorts. Path analysis models showed that earlier milestones were associated indirectly with more depressive symptoms through LGBT-related victimization. Notably, earlier ages of self-identification and disclosure of a sexual minority identity were also directly related to less depressive symptoms. Few generational differences in relations between constructs emerged. Findings garner initial support for the developmental collision hypothesis and suggest that LGBT-related victimization, rather than earlier milestones themselves, increases mental health vulnerability.

The long-lasting enigma of polycytidine (polyC) tract.

Long polycytidine (polyC) tracts varying in length from 50 to 400 nucleotides were first described in the 5'-noncoding region (NCR) of genomes of picornaviruses belonging to the Cardio- and Aphthovirus genera over 50 years ago, but the molecular basis of their function is still unknown. Truncation or complete deletion of the polyC tracts in picornaviruses compromises virulence and pathogenicity but do not affect replicative fitness in vitro, suggesting a role as "viral security" RNA element. The evidence available suggests that the presence of a long polyC tract is required for replication in immune cells, which impacts viral distribution and targeting, and, consequently, pathogenic progression. Viral attenuation achieved by reduction of the polyC tract length has been successfully used for vaccine strategies. Further elucidation of the role of the polyC tract in viral replication cycle and its connection with replication in immune cells has the potential to expand the arsenal of tools in the fight against cancer in oncolytic virotherapy (OV). Here, we review the published data on the biological significance and mechanisms of action of the polyC tract in viral pathogenesis in Cardio- and Aphthoviruses.

MeV-Stealth: A CD46-specific oncolytic measles virus resistant to neutralization by measles-immune human serum.

The frequent overexpression of CD46 in malignant tumors has provided a basis to use vaccine-lineage measles virus (MeV) as an oncolytic virotherapy platform. However, widespread measles seropositivity limits the systemic deployment of oncolytic MeV for the treatment of metastatic neoplasia. Here, we report the development of MeV-Stealth, a modified vaccine MeV strain that exhibits oncolytic properties and escapes antimeasles antibodies in vivo. We engineered this virus using homologous envelope glycoproteins from the closely-related but serologically non-cross reactive canine distemper virus (CDV). By fusing a high-affinity CD46 specific single-chain antibody fragment (scFv) to the CDV-Hemagglutinin (H), ablating its tropism for human nectin-4 and modifying the CDV-Fusion (F) signal peptide we achieved efficient retargeting to CD46. A receptor binding affinity of ~20 nM was required to trigger CD46-dependent intercellular fusion at levels comparable to the original MeV H/F complex and to achieve similar antitumor efficacy in myeloma and ovarian tumor-bearing mice models. In mice passively immunized with measles-immune serum, treatment of ovarian tumors with MeV-Stealth significantly increased overall survival compared with treatment with vaccine-lineage MeV. Our results show that MeV-Stealth effectively targets and lyses CD46-expressing cancer cells in mouse models of ovarian cancer and myeloma, and evades inhibition by human measles-immune serum. MeV-Stealth could therefore represent a strong alternative to current oncolytic MeV strains for treatment of measles-immune cancer patients.

Associations of adverse and protective childhood experiences with thwarted belongingness, perceived burdensomeness, and suicide risk among sexual minority men.

BACKGROUND: Sexual minority men (SMM) experience higher suicidal ideation and suicide attempts than the general population. We examined the associations of adverse childhood experiences (ACES) and protective and compensatory childhood experiences (PACES) with suicidal ideation and suicide attempts in adulthood via thwarted belongingness and perceived burdensomeness among SMM. METHODS: Data are from the UNITE study, a national longitudinal cohort study of HIV-negative SMM from the 50 U.S. states and Puerto Rico. Between 2017 and 2019, participants (N = 6303) completed web-based assessments at baseline and 12-month follow-up. ACES and PACES occurring before the age of 18, and current symptoms of thwarted belongingness and perceived burdensomeness were assessed at baseline. Past-week suicidal ideation and past-year suicide attempt were assessed at follow-up. RESULTS: 424 (6.7%) participants reported past-week suicidal ideation and 123 (2.0%) reported a past-year suicide attempt. The results of our multivariate model suggest that each additional adverse childhood experience was prospectively associated with 14% higher odds of past-week suicidal ideation (AOR = 1.14, 95% CI 1.09-1.19) and 19% higher odds of past-year suicide attempt (AOR = 1.19, 95% CI 1.11-1.29). Each additional protective childhood experience was prospectively associated with 15% lower odds of past-week suicidal ideation (AOR = 0.85, 95% CI 0.81-0.90) and 11% lower odds of past-year suicide attempt (AOR = 0.89, 95% CI 0.82-0.98). Perceived burdensomeness partially mediated these prospective associations. CONCLUSION: To reduce suicide, screening and treating perceived burdensomeness among SMM with high ACES may be warranted. PACES may decrease perceived burdensomeness and associated suicide risk.

Perceived parental social support and psychological control predict depressive symptoms for lesbian, gay, bisexual, transgender, queer, or questioning youth in the United States.

Salient practices in the parenting literature-support and control-have seldom been applied to understanding lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ) youth mental health. We examine associations among perceived parental social support, psychological control, and depressive symptoms for LGBTQ youth in the United States (n = 536; Mage  = 18.98; 48.1% women; 25.2% Black or African American; 37.1% Hispanic or Latino/a/x). Data were collected in 2011-2012. Results indicated joint effects of social support and psychological control predicting youth depressive symptoms. Multiple group analysis yielded a significant interaction of parenting practices for youth whose parent(s) did not know their LGBTQ identity. Findings support further consideration of parental support and control in relation to LGBTQ youth well-being.

Sexual minority youth in romantic relationships: Associations with youth well-being.

This study investigated differences in depressive symptoms, loneliness, and self-esteem for monosexual (lesbian, gay) and plurisexual (bisexual, pansexual, queer) sexual minority youth (SMY) by relationship status (single, partnered) and relationship configuration (same-gender partner, different-gender partner). Participants included 338 SMY (Mage = 19.10 years) who reported on their relationship status, partner's gender identity, well-being, and ability to confide in partner about LGBTQ issues. Results indicated that for plurisexual youth, single status was associated with greater loneliness; plurisexual youth with same-gender partners reported fewer depressive symptoms and marginally greater ability to confide in their partner about LGBTQ issues than those with different-gender partners. Findings reveal similarities across SMY while also highlighting some unique challenges among plurisexual youth with different-gender partners.

Age Trends in Bias-Based Bullying and Mental Health by Sexual Orientation and Gender Identity.

Disparities in mental health and bullying between SGM youth and their heterosexual, cisgender peers are well-established. There remain questions about whether the onset and progression of these disparities differ across adolescence-knowledge critical for screening, prevention, and intervention. To address this, the current study estimates age-based patterns of homophobic bullying, gender-based bullying, and mental health across groups of adolescents defined by sexual orientation and gender identity (SOGI). Data are from the 2013-2015 cycle of the California Healthy Kids Survey (n = 728,204). We estimated the age-specific prevalence rates of past-year homophobic bullying, gender-based bullying, and depressive symptoms using three- and two-way interactions by (1) age, sex, and sexual identity and (2) age and gender identity, respectively. We also tested how adjustments for bias-based bullying alter predicted prevalence rates of past-year mental health symptoms. Results showed that SOGI differences in homophobic bullying, gender-based bullying, and mental health were already present among youth aged 11 and younger. SOGI differences by age were attenuated when adjusting models for homophobic and gender-based bullying, particularly among transgender youth. SOGI-related bias-based bullying and mental health disparities were present early and generally persisted throughout adolescence. Strategies that prevent exposure to homophobic and gender-based bullying would significantly reduce SOGI-related disparities in mental health across adolescence.

Examination of the "model minority" stereotype through ethnicity and sexual orientation heterogeneity among Asian American youth.

INTRODUCTION: The "model minority" stereotype disguises heterogeneity among Asian American youth, many of whom are harmed by policies and attitudes that assume this population to be uniformly high achieving and "problem free." The current study uses an intersectional lens to disaggregate this population by ethnicity and sexual orientation subgroups to demonstrate differences in academic performance and substance use behavior among Asian American youth. This study also investigates the extent to which racial/ethnicity and sexual orientation-based bullying may explain such links. METHODS: Participants included 65,091 Asian American youth (46.41% Southeast Asian; 37.01% East Asian; 16.58% South Asian) in grades 6-12, who were part of the California Healthy Kids Survey (2015-2017). Participants were 49.4% female and about a third each were in grades 6-8, grades 9-10, and grades 11-12. School-based surveys were administered. Youth reported on substance use, grades, and bias-based bullying experiences in the past 12 months. RESULTS: Generalized linear mixed-effects model results showed that outcomes varied widely across youth ethnicity and sexual orientation subgroups. Inclusion of racial/ethnic and sexual orientation bullying in these models attenuated the direct effects between ethnic and sexual identities and academic performance and substance use outcomes. CONCLUSIONS: Implications of this work suggest that research and policy should not treat Asian American students as uniformly high-performing and low-risk, because the experiences of those who deviate from these assumptions will be left undetected. Interventions targeting bias-based bullying may be able to reduce disparities in academic and substance use outcomes among Asian American youth.

Interpersonal- and Community-Level Risk Factors for Adolescent Obesity: An Examination of Sexual Identity, School Violence, and School Climate in a Large Sample of Urban Adolescents.

Sexual minority adolescents are more likely to have obesity compared to their heterosexual peers, but little is known about potential contributors to this disparity that lie outside of individual-level health behaviors, such as diet and exercise. One possible contributor is school violence victimization, a factor associated with overweight/obesity in adolescence. Another possible contributor is school climate, which is associated with feelings of safety and connectedness that can lower the likelihood of school violence victimization. Moreover, even less is known about relationships among all these factors among sexual minority adolescents. This gap in the literature was addressed by analyzing CDC's district-level data from the Youth Risk Behavior Survey and School Health Profiles (N = 60,625; 50.9% female, Mage = 16 years, 84.7% heterosexual, 15.3% sexual minority). Using multilevel mixed effects logistic regression models and controlling for covariates, it was found that among females and males, those with 2+ counts of last 12-month school violence victimization had higher odds of obesity than those with no school violence victimization (AOR = 1.33; AOR = 1.24). Furthermore, females and males in more positive LGBTQ school climates had lower odds of obesity than those in less positive school climates (AOR = 0.84; AOR = 0.85). There were no sexual identity differences in these models. Findings support the careful consideration of school violence victimization and LGBTQ school climate in future obesity prevention initiatives.

Sexual minority youth's mental health and substance use: The roles of victimization, cybervictimization, and non-parental adult support.

Victimization is a well-established driver of sexual minority youth's (SMY) mental health and substance use risk. The current study examined and extended this research by exploring how victimization, cybervictimization, and non-parental supportive adults contribute to SMY's vulnerability to poor mental health and substance use. Using data from the first representative sample of Texas youth that measures sexual identity, we analyzed sex-stratified models of the association between sexual identity, mental health, and substance use, and the confounding effects of victimization, cybervictimization, and non-parental adult support. Victimization was more common among SMY and accounted for a greater proportion of sexual identity disparities on mental health and substance use, especially for males. Sexual minority females were more likely to report cybervictimization than heterosexual youth, and cybervictimization was associated with mental health risk. SMY reported fewer available non-parental supportive adults, which was associated with more sadness, suicidality, and polysubstance use. Our study adds to extant evidence that victimization drives SMY's increased susceptibility to mental health and substance use risk. Schools should implement inclusive policies that prohibit bullying based on sexual minority identity and offer professional development opportunities for supporting SMY.

Oncolytic Foamy Virus - generation and properties of a nonpathogenic replicating retroviral vector system that targets chronically proliferating cancer cells.

Nonpathogenic retroviruses of the Spumaretrovirinae subfamily can persist long-term in the cytoplasm of infected cells, completing their lifecycle only after the nuclear membrane dissolves at the time of cell division. Since the targeting of slowly dividing cancer cells remains an unmet need in oncolytic virotherapy we constructed a replication competent Foamy Virus vector (oFV) from the genomes of two chimpanzee Simian Foamy Viruses (PAN1 and PAN2) and inserted a GFP transgene in place of the bel-2 open reading frame. oFV-GFP infected and propagated with slow kinetics in multiple human tumor cell lines, inducing a syncytial cytopathic effect. Infection of growth arrested MRC5 cells was not productive, but oFV genomes persisted in the cytoplasm and the productive viral lifecycle resumed when cell division was later restored. In vivo, the virus propagated extensively in intraperitoneal ovarian cancer xenografts, slowing tumor growth, significantly prolonging survival of the treated mice and sustaining GFP transgene expression for at least 45 days. Our data indicate that oFV is a promising new replication-competent viral and gene delivery platform for efficient targeting of the most fundamental trait of cancer cells, their ability to sustain chronic proliferation.Significance:The infectivity of certain retroviruses is limited to dividing cells, which makes them attractive tools for targeting cancer cell proliferation. Previously developed replication-competent gammaretroviral vectors spread efficiently in rapidly dividing cancer cells, but not in cancer cells that divide more slowly. In contrast to rapidly proliferating transplantable mouse tumors, slow proliferation is a hallmark of human cancers and may have contributed to the clinical failure of the preclinically promising Murine Leukemia Virus vector Toca511 which failed to show efficacy in a phase 3 clinical trial in patients with glioblastoma. The studies presented in our manuscript show that oncolytic Foamy Virus (oFV) vectors are capable of persisting unintegrated in quiescent cells and resuming their life cycle once the cells start dividing again. This property of oFVs, together with their lack of pathogenicity and their ability to catalyze the fusion of infected cancer cells, makes them an attractive platform for further investigation.

Social Change and the Health of Sexual Minority Individuals: Do the Effects of Minority Stress and Community Connectedness Vary by Age Cohort?

This study examined the extent to which social stress stemming from a stigmatized social status (i.e., minority stress) was associated with three domains of health in younger as compared with older age cohorts of sexual minority individuals. Data were analyzed from the Generations Study, a longitudinal study using a probability sample (N = 1518) of age cohorts of sexual minority individuals in the USA. Exposure to a variety of minority stressors was associated with poorer health for all age cohorts. We hypothesized that because of improved social and legal environments in recent years, the associations between minority stress and health would be diminished in the younger cohort. As expected, we found that the associations between some minority stressors and health outcomes were diminished in the younger cohort compared to older cohorts. Positive associations between community connectedness and mental health and social well-being were observed for all participants but were attenuated in the younger cohort. Findings demonstrate the continuing negative association between minority stress and health among sexual minorities, which, despite some attenuation, persists even for young cohorts of sexual minority individuals in a more equal and accepting social climate.

Improved Noninvasive In Vivo Tracking of AAV-9 Gene Therapy Using the Perchlorate-Resistant Sodium Iodide Symporter from Minke Whale.

The sodium iodide symporter (NIS) is widely used as a reporter gene to noninvasively monitor the biodistribution and durability of vector-mediated gene expression via gamma scintigraphy, single-photon emission computed tomography (SPECT), and positron-emission tomography (PET). However, the approach is limited by background signal due to radiotracer uptake by endogenous NIS-expressing tissues. In this study, using the SPECT tracer pertechnetate (99mTcO4) and the PET tracer tetrafluoroborate (B18F4), in combination with the NIS inhibitor perchlorate, we compared the transport properties of human NIS and minke whale (Balaenoptera acutorostrata scammoni) NIS in vitro and in vivo. Based on its relative resistance to perchlorate, the NIS protein from minke whale appeared to be the superior candidate reporter gene. SPECT and PET imaging studies in nude mice challenged with NIS-encoding adeno-associated virus (AAV)-9 vectors confirmed that minke whale NIS, in contrast to human and endogenous mouse NIS, continues to function as a reliable reporter even when background radiotracer uptake by endogenous NIS is blocked by perchlorate.