Outness, Acceptance, and Victimization: A Longitudinal Study of Depressive Symptoms and Suicidality of Lesbian, Gay, and Bisexual and Transgender and Gender Diverse Youth.

PURPOSE: LGBTQ+ youth are at higher risk for poorer mental health. Studies are typically cross-sectional and categorize cisgender lesbian, gay, and bisexual (LGB) and transgender and gender diverse (TGD) youth as a combined group (i.e., LGBTQ+). There is a need for longitudinal studies that examine differences between LGB and TGD youth for a better understanding of their mental health needs. METHODS: Data come from a 4-wave longitudinal community-based study collected between 2011 and 2015. Hierarchical Linear Models examined trajectories of depressive symptoms and suicidality, comparing LGB and TGD youth. Between-person and within-person associations were examined, accounting for cumulative experiences of victimization, outness to family, and family acceptance in association with depressive symptoms and suicidality. RESULTS: The study included a diverse sample of 543 LGB and 118 TGD youth. Although TGD youth had, overall, higher levels of depression and suicidality, both LGB and TGD youth experienced improvement in mental health. Youth who were more out and accepted in family were less depressed and suicidal than youth who were less out and accepted in family. Within individuals, when youth become more out and accepted in family, they concurrently reported less depressive symptoms. The accumulation of victimization experiences was associated with higher levels of depression and suicidality, and more depression for youth across time. DISCUSSION: TGD youth face higher stigmatization than LGB youth, contributing to poorer mental health and disparities. Findings suggest that both LGB and TGD youth develop resilience despite victimization, and many find support within their families to cope with stigma.

Adverse Childhood Experiences, Perceived Discrimination, and Mental Health in Sexual and Gender Minoritized Adults: Comparing Stress Accumulation and Stress Sensitization Models.

Purpose: The purpose of this study was to assess the relationship between adverse childhood experiences (ACEs) exposure, perceived discrimination, and anxiety and depressive symptoms in sexual and gender minoritized (SGM) adults in the United States. Methods: Respondents (n = 4445) from a national Qualtrics research panel completed a web-based survey. Guided by the stress proliferation (mediation model) and stress sensitization (moderation model) models, we examined the relationships between ACEs and perceived discrimination and the severity of anxiety and depressive symptoms in adulthood. Results: Cumulative ACEs exposure was positively associated with everyday discrimination scale (EDS) scores. ACEs and EDS scores had a significant direct association with anxiety and depressive symptoms. We found support for EDS as a mediator for anxiety (ß = 0.12, p < 0.001) and depressive symptoms (ß = 0.14, p < 0.001) and for ACEs as a moderator of the relationship between EDS and anxiety (ß = -0.04, p = 0.004) and depressive (ß = -0.05, p = 0.001) symptoms. Conclusions: These findings suggest that both stress proliferation and stress sensitization likely contribute to disparities in anxiety and depressive symptoms in SGM adults. This finding supports the integration of social safety and minority stress perspectives regarding health disparities in SGM populations. Exposure to early life adversity likely alters neurodevelopment, which in turn increases awareness of the lack of social safety in adulthood, reduces capacity to cope with minority stress exposure, and ultimately contributes to increased anxiety and depressive symptoms. Prevention efforts should focus on building positive and compensatory childhood experiences.

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.

Smoldering oncolysis by foamy virus carrying CD19 as a CAR target escapes CAR T detection by genomic modification.

Chimeric antigen receptor (CAR) T cells have had limited success against solid tumors. Here, we used an oncolytic foamy virus (oFV) to display a model CAR target antigen (CD19) on tumors in combination with anti-CD19 CAR T cells. We generated oFV-Δbel2 and oFV-bel2 vectors to test the efficiency and stability of viral/CD19 spread. While both viruses conferred equal CAR T killing in vitro, the oFV-Δbel2 virus acquired G-to-A mutations, whereas oFV-bel2 virus had genome deletions. In subcutaneous tumor models in vivo, CAR T cells led to a significant decrease in oFV-specific bioluminescence, confirming clearance of oFV-infected tumor cells. However, the most effective therapy was with high-dose oFV in the absence of CAR T cells, indicating that CAR T clearance of oFV was detrimental. Moreover, in tumors that escaped CAR T cell treatment, resurgent virus contained deletions within the oFV-CD19 transgene, allowing the virus to escape CAR T elimination. Therefore, oFV represents a slow smoldering type of oncolytic virus, whose chronic spread through tumors generates anti-tumor therapy, which is abolished by CAR T therapy. These results suggest that further development of this oncolytic platform, with additional immunotherapeutic arming, may allow for an effective combination of chronic oncolysis.

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.

Progressive inner retinal neurodegeneration in non-proliferative macular telangiectasia type 2.

PURPOSE: Patients with non-proliferative macular telangiectasia type 2 (MacTel) have ganglion cell layer (GCL) and nerve fibre layer (NFL) loss, but it is unclear whether the thinning is progressive. We quantified the change in retinal layer thickness over time in MacTel with and without diabetes. METHODS: In this retrospective, multicentre, comparative case series, subjects with MacTel with at least two optical coherence tomographic (OCT) scans separated by >9 months OCTs were segmented using the Iowa Reference Algorithms. Mean NFL and GCL thickness was computed across the total area of the early treatment diabetic retinopathy study grid and for the inner temporal region to determine the rate of thinning over time. Mixed effects models were fit to each layer and region to determine retinal thinning for each sublayer over time. RESULTS: 115 patients with MacTel were included; 57 patients (50%) had diabetes and 21 (18%) had a history of carbonic anhydrase inhibitor (CAI) treatment. MacTel patients with and without diabetes had similar rates of thinning. In patients without diabetes and untreated with CAIs, the temporal parafoveal NFL thinned at a rate of -0.25±0.09 µm/year (95% CI [-0.42 to -0.09]; p=0.003). The GCL in subfield 4 thinned faster in the eyes treated with CAI (-1.23±0.21 µm/year; 95% CI [-1.64 to -0.82]) than in untreated eyes (-0.19±0.16; 95% CI [-0.50, 0.11]; p<0.001), an effect also seen for the inner nuclear layer. Progressive outer retinal thinning was observed. CONCLUSIONS: Patients with MacTel sustain progressive inner retinal neurodegeneration similar to those with diabetes without diabetic retinopathy. Further research is needed to understand the consequences of retinal thinning in MacTel.

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.

Binge Drinking Disparities by Grade, Race and Ethnicity, Sexual Orientation, and Gender Identity.

BACKGROUND AND OBJECTIVES: Binge drinking disparities between sexual and gender minority (SGM) students and their heterosexual, cisgender peers are well-established. Data limitations have precluded understandings of whether the onset and progression of these disparities differ by grade. Additionally, little is known about whether and how SGM-related binge drinking varies across groups of students coincidingly defined by sexual orientation or gender identity (SOGI), race, and ethnicity. In the current study, we used a large, statewide sample of secondary school students in California to describe the prevalence of binge drinking among subgroups of adolescents at the intersections of grade, race and ethnicity, and SOGI. METHODS: Data were from the 2017-2019 cycle of the California Healthy Kids Survey, one of the largest statewide cross-sectional surveys of secondary school students in the United States (n = 925 744). We described the grade-specific prevalence rates of past 30-day binge drinking by (1) grade level, (2) race and ethnicity, and (3) SOGI. Predicted probabilities estimated adjusted percentages of students' binge drinking by subgroups. RESULTS: SGM-related binge drinking differences were present early in secondary school. Several subgroups of SGM adolescents with minoritized racial and ethnic identities reported higher binge drinking rates relative to their same-grade, white, non-SGM peers. CONCLUSIONS: Prevention and intervention programs must consider developmentally- and culturally-informed strategies to most effectively promote health among minoritized students.

Sexual Identity Continuity and Change in a U.S. National Probability Sample of Sexual Minority Adults: Associations With Mental Health and Problematic Substance Use.

OBJECTIVE: Sexual minority disparities in behavioral health (e.g., mental health and substance use) are well-established. However, sexual identity is dynamic, and changes are common across the life course (e.g., identifying with a monosexual [lesbian or gay] label and later with a plurisexual [queer, pansexual, etc.] label). This study assessed whether behavioral health risks coincide with sexual identity change among sexual minority people. METHODS: Associations in a 3-year U.S. national probability sample of sexual minority adults were assessed between sexual minority identity change (consistently monosexual [N=400; 44.3% weighted], consistently plurisexual [N=239; 46.7% weighted], monosexual to plurisexual [N=19; 4.2% weighted], and plurisexual to monosexual [N=25; 4.8% weighted]) and five behavioral health indicators (psychological distress, social well-being, number of poor mental health days in the past month, problematic alcohol use, and problematic use of other drugs), controlling for demographic characteristics and baseline behavioral health. RESULTS: Among female participants, monosexual-to-plurisexual identity change (vs. consistently monosexual identity) was associated with greater psychological distress (B=3.41, SE=1.13), lower social well-being (B=-0.61, SE=0.25), and more days of poor mental health in the past month (B=0.69 [Bexp=1.99], SE=0.23). Among male participants, plurisexual-to-monosexual identity change (vs. consistently plurisexual identity) was associated with lower social well-being (B=-0.56, SE=0.25), and identity change (regardless of type) was generally associated with increased problematic use of alcohol and other drugs. CONCLUSIONS: Sexual identity change is an important consideration for sexual minority behavioral health research, with changes (vs. consistency) in identity being an important risk factor for compromised behavioral health. Prevention and treatment interventions may need to tailor messaging to sexual minority men and women differently.

Comparative long-term outcomes of vitrectomy combined with anterior chamber intraocular lens to intra-scleral haptic fixation of posterior chamber intraocular lens.

PURPOSE: To evaluate the long-term clinical outcomes in patients with combined pars plana vitrectomy (PPV) with anterior chamber intraocular lens (ACIOL) to intrascleral haptic fixation (ISHF) using the Agarwal technique with fibrin glue to secure the scleral flap of a posterior chamber intraocular lens. METHODS: Retrospective, consecutive, single-center, comparative case series. 83 eyes were studied. Patients with < 8 months of follow-up were excluded. Detailed pre-, intra-, and post-operative complications were analyzed using mixed model univariate analysis and t-test. Pre- and post-operative best corrected visual acuity (BCVA) was analyzed. RESULTS: Twenty-five subjects met entry criteria. Mean age at time of surgery was 70.4 ± 17.7 years in the ACIOL group (n = 12) and 54.6 ± 21.1 years in the ISHF group (n = 13; p = 0.03). Mean follow-up was 38.2 months. Incidence of corneal decompensation was similar in the ACIOL and ISHF lens group (p = 0.93). There was no difference in the BCVA mean change or cystoid macular edema (CME) at the final visit between the groups (p = 0.47; p = 0.08), but there was a trend toward increased CME in the ACIOL group. CONCLUSIONS: PPV with concomitant placement of either ACIOL or ISHF lens result in improvement in BCVA. Both procedures are well tolerated and result in favorable outcomes with long-term follow-up though varying patient populations do not allow precise comparison between the two groups.

DNA barcodes from over-a-century-old type specimens shed light on the taxonomy of a group of rare butterflies (Lepidoptera: Nymphalidae: Calinaginae).

We analyzed COI barcode sequences from 138 over-a-century old specimens of Calinaga including 36 name-bearing type specimens stored at the Natural History Museum London. These new data, combined with previously available RPS5 sequences, divide the Calinaga samples into four well-supported mitochondrial lineages that together with a novel wing-pattern analysis, support the recognition of six species (lhatso, buddha, brahma, aborica, formosana and davidis), with all other names subsumed either as subspecies or synonyms. One new taxon is described, Calinaga aborica naima Vane-Wright, ssp. n.

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.

Trajectories of Gender Identity and Depressive Symptoms in Youths.

Importance: Concerns about the mental health of youths going through gender identity transitions have received increased attention. There is a need for empirical evidence to understand how transitions in self-reported gender identity are associated with mental health. Objective: To examine whether and how often youths changed self-reported gender identities in a longitudinal sample of sexual and gender minority (SGM) youths, and whether trajectories of gender identity were associated with depressive symptoms. Design, Setting, and Participants: This cohort study used data from 4 waves (every 9 months) of a longitudinal community-based study collected in 2 large cities in the US (1 in the Northeast and 1 in the Southwest) between November 2011 and June 2015. Eligible participants included youths who self-identified as SGM from community-based agencies and college groups for SGM youths. Data analysis occurred from September 2022 to June 2023. Exposure: Gender identity trajectories and gender identity variability. Main Outcomes and Measures: The Beck Depression Inventory for Youth (BDI-Y) assessed depressive symptoms. Gender identity variability was measured as the number of times participants' gender identity changed. Hierarchical linear models investigated gender identity trajectories and whether gender identity variability was associated with depressive symptoms over time. Results: Among the 366 SGM youths included in the study (mean [SD] age, 18.61 [1.71] years; 181 [49.4%] assigned male at birth and 185 [50.6%] assigned female at birth), 4 gender identity trajectory groups were identified: (1) cisgender across all waves (274 participants ), (2) transgender or gender diverse (TGD) across all waves (32 participants), (3) initially cisgender but TGD by wave 4 (ie, cisgender to TGD [28 participants]), and (4) initially TGD but cisgender by wave 4 (ie, TGD to cisgender [32 participants]). One in 5 youths (18.3%) reported a different gender identity over a period of approximately 3.5 years; 28 youths varied gender identity more than twice. The cisgender to TGD group reported higher levels of depression compared with the cisgender group at baseline (Β = 4.66; SE = 2.10; P = .03), but there was no statistical difference once exposure to lesbian, gay, bisexual, and transgender violence was taken into account (Β = 3.31; SE = 2.36; P = .16). Gender identity variability was not associated with within-person change in depressive symptoms (Β = 0.23; SE = 0.74; P = .75) or the level of depressive symptoms (Β = 2.43; SE = 2.51; P = .33). Conclusions: These findings suggest that gender identity can evolve among SGM youths across time and that changes in gender identity are not associated with changes in depressive symptoms. Further longitudinal work should explore gender identity variability and adolescent and adult health.

A Coalescing Filter for Liquid-Liquid Separation and Multistage Extraction in Continuous-Flow Chemistry.

Presented here is the design and performance of a coalescing liquid-liquid filter, based on low-cost and readily available meltblown nonwoven substrates for separation of immiscible phases. The performance of the coalescer was determined across three broad classes of fluid mixtures: (i) immiscible organic/aqueous systems, (ii) a surfactant laden organic/aqueous system with modification of the type of emulsion and interfacial surface tension through the addition of sodium chloride, and (iii) a water-acetone/toluene system. The first two classes demonstrated good performance of the equipment in effecting separation, including the separation of a complex emulsion system for which a membrane separator, operating through transport of a preferentially wetting fluid through the membrane, failed entirely. The third system was used to demonstrate the performance of the separator within a multistage liquid-liquid counterflow extraction system. The performance, robust nature, and scalability of coalescing filters should mean that this approach is routinely considered for liquid-liquid separations and extractions within the fine chemical and pharmaceutical industry.

Nonwoven Reinforced Photocurable Poly(glycerol sebacate)-Based Hydrogels.

Implantable hydrogels should ideally possess mechanical properties matched to the surrounding tissues to enable adequate mechanical function while regeneration occurs. This can be challenging, especially when degradable systems with a high water content and hydrolysable chemical bonds are required in anatomical sites under constant mechanical stimulation, e.g., a foot ulcer cavity. In these circumstances, the design of hydrogel composites is a promising strategy for providing controlled structural features and macroscopic properties over time. To explore this strategy, the synthesis of a new photocurable elastomeric polymer, poly(glycerol-co-sebacic acid-co-lactic acid-co-polyethylene glycol) acrylate (PGSLPA), is investigated, along with its processing into UV-cured hydrogels, electrospun nonwovens and fibre-reinforced variants, without the need for a high temperature curing step or the use of hazardous solvents. The mechanical properties of bioresorbable PGSLPA hydrogels were studied with and without electrospun nonwoven reinforcement and with varied layered configurations, aiming to determine the effects of the microstructure on the bulk compressive strength and elasticity. The nonwoven reinforced PGSLPA hydrogels exhibited a 60% increase in compressive strength and an 80% increase in elastic moduli compared to the fibre-free PGSLPA samples. The mechanical properties of the fibre-reinforced hydrogels could also be modulated by altering the layering arrangement of the nonwoven and hydrogel phase. The nanofibre-reinforced PGSLPA hydrogels also exhibited good elastic recovery, as evidenced by the hysteresis in compression fatigue stress-strain evaluations showing a return to the original dimensions.

Interpersonal protective factors for LGBTQ+ youth at multiple intersecting social identities and positions.

Interpersonal supports are protective against multiple negative health outcomes for youth such as emotional distress and substance use. However, finding interpersonal support may be difficult for youth exposed to intersecting racism, heterosexism, and cisgenderism, who may feel they are "outsiders within" their multiple communities. This study explores disparities in interpersonal supports for youth at different sociodemographic intersections. The 2019 Minnesota Student Survey includes data from 80,456 high school students, including measures of four interpersonal supports: feeling cared about by parents, other adult relatives, friends, and community adults. Exhaustive Chi-square Automatic Interaction Detection analysis was used to examine all interactions among four social identities/positions (racialized/ethnic identity, sexual identity, gender identity, sex assigned at birth) to identify groups who report different rates of caring from each source (Bonferroni adjusted p<.05). In the overall sample, 69.24% perceived the highest level of caring ("very much") from parents, 50.09% from other adult relatives, 39.94% from friends, and 15.03% from community adults. Models identified considerable differences in each source of support. For example, more than 72% of straight, cisgender youth reported their parents cared about them very much, but youth who identified as LGBQ and TGD or gender-questioning were much less likely to report high parent caring (less than 36%) across multiple racialized/ethnic identities and regardless of sex assigned at birth. Findings highlight the importance of better understanding the ways interpersonal support might differ across groups, and underscore a need for intersectionality-tailored interventions to develop protective interpersonal supports for LGBTQ+ youth, rather than one-size-fits-all approaches.

Oncolytic varicella-zoster virus engineered with ORF8 deletion and armed with drug-controllable interleukin-12.

BACKGROUND: The varicella-zoster virus (VZV), belonging to the group of human α-herpesviruses, has yet to be developed as a platform for oncolytic virotherapy, despite indications from clinical case reports suggesting a potential association between VZV infection and cancer remission. METHODS: Here, we constructed oncolytic VZV candidates based on the vaccine strain vOka and the laboratory strain Ellen. These newly engineered viruses were subsequently assessed for their oncolytic properties in the human MeWo melanoma xenograft model and the mouse B16-F10-nectin1 melanoma syngeneic model. RESULTS: In the MeWo xenograft model, both vOka and Ellen exhibited potent antitumor efficacy. However, it was observed that introducing a hyperfusogenic mutation into glycoprotein B led to a reduction in VZV's effectiveness. Notably, the deletion of ORF8 (encodes viral deoxyuridine triphosphatase) attenuated the replication of VZV both in vitro and in vivo, but it did not compromise VZV's oncolytic potency. We further armed the VZV Ellen-ΔORF8 vector with a tet-off controlled mouse single-chain IL12 (scIL12) gene cassette. This augmented virus was validated for its oncolytic activity and triggered systemic antitumor immune responses in the immunocompetent B16-F10-nectin1 model. CONCLUSIONS: These findings highlight the potential of using Ellen-ΔORF8-tet-off-scIL12 as a novel VZV-based oncolytic virotherapy.

Being out in high school: Positive implications for well-being in three U.S. cohorts of sexual minority adults.

For lesbian, gay, bisexual, or queer (i.e., sexual minority [SM]) youth, coming out is an important developmental milestone and is typically associated with positive well-being. However, coming out in high school may entail a higher risk of school-based victimization. Due to the greater risk of homophobic bullying, the implications of being out in adolescence and well-being later in adulthood remain unclear. Using data from a national probability survey (Generations Study) of three distinct age cohorts of SM adults (N = 1,474) in the United States, this study (a) examined how being out at school in adolescence affects general well-being in adulthood and (b) SM-specific well-being in adulthood, and (c) examined if these associations differ by cohort. Results from multivariate regression analyses demonstrated that being out in adolescence was not significantly associated with general well-being, but was significantly associated with SM-specific well-being: higher rates of identity centrality and community connectedness, and lower rates of internalized homophobia. There were no cohort differences in the associations between outness in high school, general well-being, and SM well-being. The findings from this national probability sample of SM adults provide novel insight into implications of being out across the life course, including the positive implications of being out at school in adolescence for SM-specific well-being in adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.