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.

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.

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.

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).

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.

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.

Unaccompanied unstable housing among racially, ethnically, sexually, and gender diverse youth: Intersecting identities bearing the greatest burden.

Disparities in youth homelessness by racial/ethnic, sexual, and gender identities are well documented, though this literature lacks specificity regarding intersectional social identities of youth who are most likely to experience homelessness. Population-based cross-sectional data on youth from the 2019 Minnesota Student Survey (N = 80,456) were used to examine the relationship between parent caring and intersections of minoritized identities that experience the highest prevalence of two distinct types of unaccompanied unstable housing with expanded categories of sexual and gender identities. Exhaustive chi-square automatic interaction detection models revealed that low parent caring was the most common predictor of unaccompanied homelessness and running away, but there was important variation among youth of color at the intersection of sexual and gender identities. The findings reveal a more complex story of disparities in unaccompanied unstable housing among youth with multiple marginalized social identities and highlight the need to create culturally informed prevention and intervention strategies for parents of LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and questioning) youth of color. The implications for prevention and intervention among subgroups with the highest prevalence are discussed in the context of interlocking systems of power and oppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Surface-modified measles vaccines encoding oligomeric, prefusion-stabilized SARS-CoV-2 spike glycoproteins boost neutralizing antibody responses to Omicron and historical variants, independent of measles seropositivity.

Serum titers of SARS-CoV-2-neutralizing antibodies (nAbs) correlate well with protection from symptomatic COVID-19 but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are lifelong after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We, therefore, sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain, and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated the potent induction of high titer nAbs in measles-immune mice and confirmed the significant contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin display of the SARS-CoV-2 spike glycoprotein. In animals primed and boosted with a measles virus (MeV) vaccine encoding the ancestral SARS-CoV-2 spike, high-titer nAb responses against ancestral virus strains were only weakly cross-reactive with the Omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the Omicron BA.1 spike, antibody titers to both ancestral and Omicron strains were robustly elevated, and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that by engineering the antigen, we can develop potent measles-based vaccine candidates against SARS-CoV-2.IMPORTANCEAlthough the live-attenuated measles virus (MeV) is one of the safest and most efficacious human vaccines, a measles-vectored COVID-19 vaccine candidate expressing the SARS-CoV-2 spike failed to elicit neutralizing antibody (nAb) responses in a phase-1 clinical trial, especially in measles-immune individuals. Here, we constructed a comprehensive panel of MeV-based COVID-19 vaccine candidates using a MeV with extensive modifications on the envelope glycoproteins (MeV-MR). We show that artificial trimerization of the spike is critical for the induction of nAbs and that their magnitude can be significantly augmented when the spike protein is synchronously fused to a dodecahedral scaffold. Furthermore, preexisting measles immunity did not abolish heterologous immunity elicited by our vector. Our results highlight the importance of antigen optimization in the development of spike-based COVID-19 vaccines and therapies.

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.

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).

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.

Examining Mental Health and Bullying Concerns at the Intersection of Sexuality, Gender, Race, and Ethnicity Among a National Sample of Sexual and Gender Diverse Youth.

Purpose: Most extant scholarship that examines the health experiences of sexual and gender diverse youth (SGDY) is limited in the ability to apply an intersectional framework due to small sample sizes and limitations in analytic methods that only analyze the independent contribution of social identities. To address this gap, this study explored the well-being of youth at the intersection of ethnic, racial, sexual, and gender identities in relation to mental health and bullying. Methods: Data were from a U.S. national survey of SGDY aged 13-18 years, collected in 2022 (N = 12,822). Exhaustive Chi-square Automatic Interaction Detection analysis identified intersectional social positions bearing the greatest burden of negative health-related experiences (depression, anxiety, and past 30-day in-person victimization). Results: Transgender boys were among those at the highest prevalence for compromised mental health and peer-based in-person victimization. Although the primary distinguishing factor was transgender identity for depression and anxiety, there were no racial/ethnic distinctions, corroborating some previous scholarship. Asian cisgender and transgender girl SGDY shared the lowest burden of peer-based in-person victimization in school. Conclusion: Our findings suggest a need for scholars, health professionals, and other stakeholders to better understand the mechanisms that drive negative health experiences and in-person victimization experiences at the intersections of sexual, gender, racial, and ethnic identities.

CRISPRi-Mediated Treatment of Dominant Rhodopsin-Associated Retinitis Pigmentosa.

Rhodopsin (RHO) mutations such as Pro23His are the leading cause of dominantly inherited retinitis pigmentosa in North America. As with other dominant retinal dystrophies, these mutations lead to production of a toxic protein product, and treatment will require knockdown of the mutant allele. The purpose of this study was to develop a CRISPR-Cas9-mediated transcriptional repression strategy using catalytically inactive Staphylococcus aureus Cas9 (dCas9) fused to the Krüppel-associated box (KRAB) transcriptional repressor domain. Using a reporter construct carrying green fluorescent protein (GFP) cloned downstream of the RHO promoter fragment (nucleotides -1403 to +73), we demonstrate a ∼74-84% reduction in RHO promoter activity in RHOpCRISPRi-treated versus plasmid-only controls. After subretinal transduction of human retinal explants and transgenic Pro23His mutant pigs, significant knockdown of rhodopsin protein was achieved. Suppression of mutant transgene in vivo was associated with a reduction in endoplasmic reticulum (ER) stress and apoptosis markers and preservation of photoreceptor cell layer thickness.