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Abstract Background LGBTQ-affirmative cognitive-behavioral therapy (CBT) is an evidence-based treatment for reducing transdiagnostic mental and behavioral health concerns among LGBTQ individuals. Preserving the effects of this intervention as it is translated into practice can maximize public health benefits. This study systematically identifies and evaluates implementation strategies for LGBTQ-affirmative CBT. Methods First, we identified and operationalized implementation strategies used across five trials of LGBTQ-affirmative CBT using the Pragmatic Implementation Reporting Tool. Second, we evaluated the relative importance of these strategies via a quantitative assessment (N = 31 unique trial implementers). Survey responses were analyzed descriptively within each trial. Across all trials, we organized strategies as (1) high priority, (2) moderate priority, and (3) optional (if resources are available) for implementing LGBTQ-affirmative CBT. Results Within each trial, we identified 20 or more implementation strategies that were used, many of which overlapped across trials. We identified nine high priority strategies (e.g., working with clients to engage them in LGBTQ-affirmative CBT), nine moderate priority strategies (e.g., conducting ongoing training in LGBTQ-affirmative CBT), and nine optional/resource dependent strategies (e.g., showing visual indicators of LGBTQ affirmation within the physical spaces where LGBTQ-affirmative CBT is delivered). Conclusions LGBTQ-affirmative CBT is a complex intervention requiring a package of implementation strategies. Our findings provide guidance for implementers in settings with different levels of resources regarding the highest priority strategies that may be needed to preserve the effectiveness of LGBTQ-affirmative CBT as it is translated into real-world settings.

Altered protein conformation can cause incurable neurodegenerative disorders. Mutations in SERPINI1, the gene encoding neuroserpin, can alter protein conformation resulting in cytotoxic aggregation leading to neuronal death. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare autosomal dominant progressive myoclonic epilepsy that progresses to dementia and premature death. We developed HEK293T and induced pluripotent stem cell (iPSC) models of FENIB, harboring a patient-specific pathogenic SERPINI1 variant or stably overexpressing mutant neuroserpin fused to GFP (MUT NS-GFP). Here, we utilized a personalized adenine base editor (ABE)-mediated approach to correct the pathogenic variant efficiently and precisely to restore neuronal dendritic morphology. ABE-treated MUT NS-GFP cells demonstrated reduced inclusion size and number. Using an inducible MUT NS-GFP neuron system, we identified early prevention of toxic protein expression allowed aggregate clearance, while late prevention halted further aggregation. To address several challenges for clinical applications of gene correction, we developed a neuron-specific engineered virus-like particle to optimize neuronal ABE delivery, resulting in higher correction efficiency. Our findings provide a targeted strategy that may treat FENIB and potentially other neurodegenerative diseases due to altered protein conformation such as Alzheimer’s and Huntington’s diseases.

Abstract Background Approximately 30% of dogs with idiopathic epilepsy (IE) are drug‐resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE. Objective To evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug‐resistant IE. Animals Fifty‐one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial. Methods Double‐blinded placebo‐controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1‐month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial. Results At the 9 mg/kg/day dose, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05). Conclusions and Clinical Importance Cannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs.

Abstract Introduction Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. Methods We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants’ perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. Results Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. Conclusion Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.

Recent evidence suggests that maternal childhood adversity may have an intergenerational impact, with children of adversity-exposed mothers exhibiting elevated symptoms of psychopathology. At the same time, many children demonstrate resilience to these intergenerational effects. Among the variety of factors that likely contribute to resilience, the composition of the gut microbiome may play a role in buffering the negative impacts of trauma and stress. The current prospective cohort study tested the novel hypothesis that offspring gut microbiome composition is a potential moderator in the relationship between maternal exposure to childhood adversity and offspring symptomatology (i.e., internalizing, externalizing, and posttraumatic stress symptoms). Maternal childhood adversity was self-reported during pregnancy via the Childhood Trauma Questionnaire and Adverse Childhood Experiences (ACEs) survey, and offspring symptomatology was assessed with the Child Behavior Checklist/1.5–5 when offspring were 2–4 years old. Offspring fecal samples were collected between these timepoints (i.e., during 6- to 24-month follow-up visits) for microbiome sequencing. Results indicated that maternal ACEs and the relative abundances of Bifidobacterium, Lactobacillus, and Prevotella were associated with offspring symptomatology. However, there was little evidence that microbial abundance moderated the association between maternal adversity and offspring symptoms. Overall, these findings further our understanding of how the gut microbiome associates with psychopathology, and informs future studies aimed at targeting modifiable factors that may buffer the intergenerational effects of childhood adversity.

Abstract Background Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. Methods We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. Results Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). Discussion In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

The purpose of this study was to evaluate plasma ondansetron (OND) concentrations in a population of dogs with naturally occurring nausea after oral OND administration. Twenty-four dogs were randomly assigned to receive one of the following doses of oral OND: 0.5 mg/kg q8h, 0.5 mg/kg q12h, 1 mg/kg q8h, or 1 mg/kg q12h. Blood samples for plasma OND measurements were collected at baseline and 2, 4, and 8 h after administration of the first dose of OND. OND concentrations averaged over an 8 h time period were not significantly different between dose groups (0.5 mg/kg group: median 8.5 ng/mL [range 1–96.8 ng/mL], 1 mg/kg group: median 7.4 ng/mL [range 1–278.7 ng/mL]). The mean maximum concentrations in the 0.5 mg/kg and 1 mg/kg groups were 35.8 ± 49.0 ng/mL and 63.3 ± 121.1 ng/mL, respectively. OND concentrations were below the lower limit of quantification (LLOQ) in 50% (18/36) of samples in the 0.5 mg/kg groups and 39% (14/36) of samples in the 1 mg/kg groups. Six dogs (6/24, 25%) did not have OND detected at any time. The mean nausea scores at baseline were similar amongst all groups and decreased over time. The bioavailability of oral OND appears to be poor. Despite low plasma OND concentrations, nausea scores improved over time.

Abstract Background Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. Methods Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. Results We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all $$p

Previous studies suggest epigenetic alterations may contribute to the association between maternal prenatal depression and adverse offspring outcomes. Developmental researchers have recently begun to examine these associations in relation to epigenetic age acceleration/deceleration, a biomarker of developmental risk that reflects the deviation between epigenetic age and chronological age. In the perinatal period, preliminary studies indicate that maternal prenatal depression may lead to epigenetic age deceleration in newborns, which may predict adverse developmental outcomes. The present study examined the relationship between maternal prenatal exposures (i.e., depression, stress, and SSRI use) and offspring epigenetic age deceleration in 303 mother-offspring dyads. Women were recruited in the first trimester of pregnancy and followed longitudinally until delivery. Maternal depression, perceived stress, and SSRI use were assessed at each prenatal visit. Newborn epigenetic age was determined via cord blood samples. Results indicated maternal prenatal stress was not associated with newborn epigenetic age deceleration (ΔR2 = 0.002; p = 0.37). Maternal prenatal depression was associated with decelerated epigenetic age (ΔR2 = 0.01, p = 0.04), but this relationship did not hold when accounting for maternal use of SSRIs (ΔR2 = 0.002, p = 0.43). Conversely, maternal SSRI use significantly predicted newborn epigenetic age deceleration over and above the influence of maternal depression (ΔR2 = 0.03, p = 0.001). These findings suggest maternal prenatal SSRI use may significantly contribute to the previously documented association between maternal prenatal depression and epigenetic age deceleration. Further studies are needed to examine how these epigenetic differences at birth may contribute to adverse outcomes in later development.

Background Vaccines are effective in preventing Coronavirus Disease 2019 (COVID-19). Vaccine hesitancy defined as delay of acceptance or refusal of the vaccine is a major barrier to effective implementation. Methods Participants were recruited statewide through an English and Spanish social media marketing campaign conducted by a local news station during a one-month period as vaccines were becoming available in Rhode Island (from December 21, 2020 to January 22, 2021). Participants completed an online survey about COVID-19 vaccines and vaccine hesitancy with constructs and items adopted from the Health Belief Model. Results A total of 2,007 individuals completed the survey. Eight percent (n = 161) reported vaccine hesitancy. The sample had a median age of 58 years (interquartile range [IQR]: 45, 67), were majority female (78%), White (96%), Non-Hispanic (94%), employed (58%), and reported an annual individual income of $50,000 (59%). COVID-19 vaccine hesitancy was associated with attitudes and behaviors related to COVID-19. A one unit increase in concern about COVID-19 was associated with a 69% (Adjusted Odds Ratio: 0.31, 95% CI: 0.26–0.37) decrease in vaccine hesitancy. A one-level increase in the likelihood of getting influenza vaccine was associated with a 55% (AOR: 0.45 95% CI: 0.41–0.50) decrease in vaccine hesitancy. Conclusions COVID-19 vaccine hesitancy was relatively low in a state-wide survey in Rhode Island. Future research is needed to better understand and tailor messaging related to vaccine hesitancy.

The COVID-19 pandemic has had a dramatic impact on global economies and societies. Although social distancing policies are needed to contain the spread and impact of COVID-19, they also impose a psychological and economic burden on people who are already experiencing increased distress such as caregivers. Yet, few measures have been developed and validated to measure the psychosocial impact of COVID-19. Utilizing item response theory (IRT), the purpose of this study was to develop and psychometrically validate a measure of psychosocial functioning—the Psychosocial Functioning during COVID-19 (PFC-19) Questionnaire—to assess changes in social interaction, mental health, health behavior, and global functioning among a sample of informal caregivers during the COVID-19 pandemic. The analytic sample ( n = 733) was recruited from Amazon Mechanic Turk (MTurk) (69% male, 55% white). Results suggest a two-factor measure, assessing global functioning (14 items) and affective response (8 items), with strong evidence for reliability, validity, and dimensionality. Future research should replicate this factor structure in other samples.

Sex is an important factor in mental health, and a non-binary view of how variation in sex and gender influence mental health represents a new research frontier that may yield new insights. The recent acceleration of research into sexual orientation, gender identity, and mental health has generally been conducted without sufficient understanding of the opinions of sexual and gender minorities (SGM) toward this research. We surveyed 768 individuals, with an enrichment of LGBTQ+ stakeholders, for their opinions regarding genetic research of SGM and mental health. We found that the key predictors of attitudes toward genetic research specifically on SGM are 1) general attitudes toward genetic and mental health research 2) tolerance of SGM and associated behaviors and 3) age of the participant. Non-heterosexual stakeholder status was significantly associated with increased willingness to participate in genetic research if a biological basis for gender identity were discovered. We also found that heterosexual, cisgender participants with a low tolerance for SGM indicated their SGM views would be positively updated if science showed a biological basis for their behaviors and identities. These findings represent an important first step in understanding and engaging the LGBTQ+ stakeholder community in the context of genetic research.

Author(s): Audrey Harkness [sup.1] , Alyssa Lozano [sup.2] , Sierra Bainter [sup.3] , Daniel Mayo [sup.3] , Daniel Hernandez Altamirano [sup.1] , Brooke G. Rogers [sup.4] , Guillermo Prado [sup.1] [...], Latino sexual minority men (LSMM) are affected by HIV and behavioral health disparities. Evidence-based HIV-prevention and behavioral health (BH) services are not sufficiently scaled up to LSMM. The current study identified multilevel barriers and facilitators to LSMM's use of HIV-prevention and BH services. LSMM (N = 290) in South Florida, a US HIV epicenter, completed a battery of measures potentially associated with pre-exposure prophylaxis (PrEP) and BH treatment use. Stochastic search variable selection (SSVS) followed by multiple linear regression analyses identified variables associated with engagement in PrEP and BH treatment. Multilevel determinants of PrEP and BH treatment engagement were identified, with most identified determinants being at the relational level (e.g., stigma, discrimination based on income and immigration status, personal recommendation for treatment). Individual (e.g., knowledge, self-efficacy) and structural (e.g., financial stress) determinants were also identified. Accordingly, modifiable leverage points to enhance the reach of PrEP and BH treatment to LSMM include educating and enhancing the perceived relevance of services, de-stigmatizing and normalizing via peer examples, bolstering self-efficacy, and building trust.

Psychosocial syndemic conditions have received more attention regarding their deleterious effects on HIV acquisition risk than for their potential impact on HIV treatment and viral suppression. To examine syndemic conditions' impact on the HIV care continuum, we analyzed data collected from people living with HIV (N = 14,261) receiving care through The Centers for AIDS Research Network of Integrated Clinical Systems at seven sites from 2007 to 2017 who provided patient-reported outcomes ∼4-6 months apart. Syndemic condition count (depression, anxiety, substance use, and hazardous drinking), sexual risk group, and time in care were modeled to predict antiretroviral therapy (ART) adherence and viral suppression (HIV RNA

IntroductionLittle is known about onward HIV transmissions from people living with HIV (PLWH) in care. Antiretroviral therapy (ART) has increased in potency, and treatment as prevention (TasP) is an important component of ending the epidemic. Syndemic theory has informed modelling of HIV risk but has yet to inform modelling of HIV transmissions.MethodsData were from 61,198 primary HIV care visits for 14,261 PLWH receiving care through the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) at seven United States (U.S.) sites from 2007 to 2017. Patient-reported outcomes and measures (PROs) of syndemic conditions - depressive symptoms, anxiety symptoms, drug use (opiates, amphetamines, crack/cocaine) and alcohol use - were collected approximately four to six months apart along with sexual behaviours (mean = 4.3 observations). Counts of syndemic conditions, HIV sexual risk group and time in care were modelled to predict estimated HIV transmissions resulting from sexual behaviour and viral suppression status (HIV RNA

Maternal stress during pregnancy can cause alterations to the fetal hypothalamus-pituitary-adrenal (HPA) axis, a phenomenon known as fetal programming that may have lasting effects on offspring outcomes, including depression. Evidence suggests that these effects may vary with respect to the offspring's genetic risk. Nonetheless, few studies have examined these effects into adulthood, when risk for depression onset is highest. The present study builds upon the extant literature by examining the interaction of maternal prenatal perceived stress (MPPS) and offspring HPA-axis polygenic risk to predict offspring depression in early adulthood. A total of 381 mother-child dyads participated in a prospective, longitudinal study that spanned from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) that reflected the additive risk of three HPA-axis candidate genes. The results indicated that the interaction of MPPS and HPA-axis MGPS confers risk for offspring depression at age 20, in line with the differential susceptibility model. This interaction may be specific to prenatal stress, as maternal stress during early childhood did not interact with genetic risk to predict depression. These findings provide the first evidence that genetic variants that are associated with the HPA axis may act in a polygenic, additive fashion to moderate the association between fetal programming and adult depression.

Sleep disorders are prevalent and interfering conditions that affect people living with HIV (PLWH) at higher rates than the general population. Lower quality sleep has been associated with poorer health-related quality of life and immune function in PWH, though sleep is typically assessed subjectively. The current study aimed to examine the association between objective sleep/wake patterns measured via actigraphy with HIV outcomes. Participants (N = 87) were recruited from a public, urban HIV clinic located in the Southeastern United States. Participants were instructed to wear actigraphy monitors for one week (Range: 5–8 days). Log viral load and absolute CD4 were obtained via medical chart review. Linear regression analyses predicting HIV RNA Viral Load (log transformed) and CD4 Count were employed with three actigraphy sleep variables: sleep efficiency, wake after sleep onset (WASO), and sleep quantity. Backward entry regression with both significant actigraphy predictors, sleep efficiency and WASO, included as predictors resulted in sleep efficiency remaining in the model and WASO being removed. Separate models revealed that each one-unit increase in sleep efficiency was associated with a b = 0.032-point decrease in the log-transformed HIV RNA viral load (p = 0.03) and for each one-unit increase in wake after sleep onset (WASO) was associated with a b = 0.35-point increase in the log-transformed HIV RNA viral load (p = 0.04). Sleep quantity, however, was not, and none were associated with absolute CD4 count. The findings add to the evidence for an association of objectively measured poorer sleep efficiency being associated with higher HIV RNA viral load. Implications for clinical practice include assessing and addressing sleep efficiency as part of comprehensive clinical HIV care. [ABSTRACT FROM AUTHOR]

Background: LGBTQ-affirmative cognitive-behavioral therapy (CBT) is an evidence-based treatment for reducing transdiagnostic mental and behavioral health concerns among LGBTQ individuals. Preserving the effects of this intervention as it is translated into practice can maximize public health benefits. This study systematically identifies and evaluates implementation strategies for LGBTQ-affirmative CBT. Methods: First, we identified and operationalized implementation strategies used across five trials of LGBTQ-affirmative CBT using the Pragmatic Implementation Reporting Tool. Second, we evaluated the relative importance of these strategies via a quantitative assessment (N = 31 unique trial implementers). Survey responses were analyzed descriptively within each trial. Across all trials, we organized strategies as (1) high priority, (2) moderate priority, and (3) optional (if resources are available) for implementing LGBTQ-affirmative CBT. Results: Within each trial, we identified 20 or more implementation strategies that were used, many of which overlapped across trials. We identified nine high priority strategies (e.g., working with clients to engage them in LGBTQ-affirmative CBT), nine moderate priority strategies (e.g., conducting ongoing training in LGBTQ-affirmative CBT), and nine optional/resource dependent strategies (e.g., showing visual indicators of LGBTQ affirmation within the physical spaces where LGBTQ-affirmative CBT is delivered). Conclusions: LGBTQ-affirmative CBT is a complex intervention requiring a package of implementation strategies. Our findings provide guidance for implementers in settings with different levels of resources regarding the highest priority strategies that may be needed to preserve the effectiveness of LGBTQ-affirmative CBT as it is translated into real-world settings. [ABSTRACT FROM AUTHOR]

Objective: The management of HIV has shifted from a focus solely on the disease to a broader perspective encompassing co-occurring medical conditions and quality of life. Mental health concerns such as depression and sleep disturbances, particularly insomnia, are often overlooked in HIV care. The aim of the study was to investigate the longitudinal impact of insomnia on depression and medication adherence among (PLWH). Methods: This study, conducted in an urban HIV clinic, involved active patients and assessed depression, insomnia, and medication adherence at baseline, 3-month, and 6-month intervals. Hierarchical linear models were employed to analyze the fixed and random effects of time, within-person and between-person insomnia on depression, as well as the effects of time, within-person and between-person depression on ART adherence. Results: Within-person effects revealed that each one unit increase in the Insomnia Severity Index (ISI) was associated with a b = 0.267-point rise in Patient Health Questionnaire-9 (PHQ-9) scores (p <.001). Between-person effects revealed that each one-point increase in an individual's average ISI score was associated with a 0.476-point elevation in their PHQ-9 scores (p <.001). The between-person effects of depression on medication adherence indicated significance, with each point increase in an individual's average PHQ-9 score being linked to a 0.36% decrease in adherence (p =.012). Conclusion: The study underscores the potential impact of insomnia on mental health and treatment adherence in people living with HIV (PLWH). This study emphasizes the necessity of comprehensive care models considering the interplay between sleep quality, mental health, and medication adherence for PLWH. [ABSTRACT FROM AUTHOR]

Background: Preexposure prophylaxis (PrEP) is an effective biological option for HIV prevention yet persistent disparities in PrEP uptake and retention exist among Hispanic/Latino men who have sex with men (MSM). We evaluated barriers and facilitators to PrEP care among Hispanic/Latino MSM at risk for and living with HIV. Setting: A small urban setting in the Northeastern United States. Methods: This was a mixed-methods, exploratory, sequential, qualitative and quantitative pilot study among Latino MSM at-risk and/or living with HIV across (1) semistructured qualitative interviews (N = 15) and (2) cross-sectional survey (N = 98). Results: Participants reported a diverse range of sexual identities, HIV statuses, and PrEP statuses. Qualitative participants described feelings of isolation in both Hispanic/Latino and queer communities that made it challenging to learn about HIV prevention or PrEP from peers. Participants in the survey indicated that they would be more inclined to uptake PrEP if PrEP were offered in primary care settings (n = 61; 62.2%); there were specific LGBTQ+ affirming medical settings (n = 36; 36.7%); and/or they could meet other people who are currently on PrEP and sharing experiences online (n = 46; 46.9%) or in person (n = 38; 38.8%). Findings were organized to reflect determinants and implementation strategies that could be used to improve PrEP uptake among this population. Conclusions: This mixed-methods study identified several challenges and opportunities for increasing the reach of PrEP to Hispanic/Latino MSM. These findings should be used to inform tailored implementation strategies to promote PrEP uptake among this at-risk yet currently underserved population. [ABSTRACT FROM AUTHOR]