The single-cell opioid responses in the context of HIV (SCORCH) consortium.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

COVID-19-related changes in outpatient CPAP setup pathways for OSA are linked with decreased 30-day CPAP usage.

The COVID-19 pandemic changed continuous positive airway pressure (CPAP) setup pathways. We evaluated patients commenced on CPAP in 2019 (prepandemic) and 2020 (post-first UK wave). Face-to-face (F2F) setup numbers, with CPAP turned on, decreased from 613 patients (98.9%) in 2019, to 6 (1.1%) in 2020. In 2020, setups were F2F without CPAP turned on (403 (71.1%)), or remote (158 (27.9%)). Prepandemic median CPAP usage at first follow-up was 5.4 (2.7-6.9) hours/night and fell by 0.9 hours/night (95% CI 0.5 to 1.2, p<0.0001) in 2020. We found clinically relevant reductions in CPAP usage with pathway changes post-COVID-19.

BDSM, Non-Monogamy, Consent, and Stigma Navigation: Narrative Experiences.

With the rise in popularity of media pieces depicting alternative sexual/relationship preferences, there has been a rise in interest in kink and BDSM (Sprott & Berkey, 2015), which corresponds with research suggesting that approximately 20% of Americans have been in a consensually non-monogamous relationship (Haupert et al., 2016). Despite this growing popularity, these populations are often stigmatized and misunderstood (Bettinger, 2002). The present study examined the self-reported experiences of individuals who have participated in kink, BDSM, non-monogamy, and/or polyamory. Specifically, the study used qualitative methodology to examine narratives of discrimination, harassment, coming out, being outed, consent violations, and/or sexual assault in a BDSM or non-monogamous encounter. Participants consisted of 67 adults who completed an online survey conducted by the National Coalition for Sexual Freedom and were asked to provide narratives of their experience. Data were analyzed using a modified consensual qualitative research methodology (CQR-M; Spangler et al., 2012). Results indicated 11 categories falling into three domains: navigating incidents (consent issues, negotiation of scenes or relationships, identity/beliefs about coming out, and reporting), contributing factors (role of social media/media, exacerbating factors, and beliefs about the community), and response/prevention (outcome of incident, emotions felt, lessons learned from incident by the participant, and what would be helpful from the community). This study contributes to our understanding of the experiences in this community and elucidates strategies that can be used to intervene and advocate for these populations, including education of the general public and deliberate community support.

Sexual violence victimization and suicide: Testing a coping-mental health framework.

Sexual violence victimization is a prevalent public health concern. However, little research has investigated the factors linking sexual violence victimization to suicidal thoughts and behaviors (STBs). The current study tested the applicability of the psychological mediation framework, a coping-mental health model, for the prevention of STBs among victims of sexual youviolence. Furthermore, the current study explored whether sexual orientation moderated the progression from sexual violence victimization to STBs. Data were drawn from an online survey of victimization experiences and health (N = 2175). Bootstrap mediation tested whether the association of sexual violence victimization and STBs was mediated by emotion regulation strategies (cognitive reappraisal and expressive suppression) and psychopathology (anxiety, depression, and posttraumatic stress disorder). Multiple-groups analysis tested whether links within the mediation effects varied by sexual orientation. Bivariate findings showed that: (1) sexual minority persons were more likely to report sexual violence victimization and (2) cognitive reappraisal was more meaningfully associated with mental health among sexual minority persons. Sexual violence victimization was associated with STBs via a serial mediation through emotion regulation and psychopathology. The association between psychopathology and STBs was stronger among sexual minority compared with heterosexual respondents. Physical violence victimization was associated with STBs for heterosexual but not sexual minority persons in a follow-up model. Findings support an emotion regulation-mental health framework for the prevention of suicide among victims of sexual violence. Research and training implications are discussed.

Cardiac arrest following protamine administration: a case series.

AIMS: Protamine sulfate is commonly used to reverse the action of heparin after catheter ablation procedures. Serious protamine-related adverse effect is rare, but its recognition and appropriate management by electrophysiologists and intensivists is important. Direct ventricular fibrillation (VF) soon after a slow infusion of protamine has not been clearly described. METHODS AND RESULTS: We examined the records of all patients who suffered apparent adverse events after protamine administration in our electrophysiology lab from 2013 to 2018. We describe a series of three patients, all of whom suffered a precipitous fall in arterial pressure followed by VF within minutes after administration of protamine following ablation for atrial fibrillation. The same supplier of protamine was used in all three cases, but they were from different batches. Serum tryptase levels were measured in all cases, immediately post-cardiac arrest and at 2- and 6-h post-event. Immunoglobulin levels were not measured. Two patients recovered after aggressive supportive therapy; the third died despite similar support. CONCLUSION: We have encountered three cases of profound hypotension followed by VF soon after administration of protamine. Although protamine is safe in a large majority of patients, these adverse events have led our centre to exercise greater selectivity and caution in its use.

Examining the Lesbian, Gay, and Bisexual Identity Scale Among Members of an Alternative Sexuality Special Interest Group.

The present study contributes to a growing body of literature developing psychometrically and theoretically grounded measures of sexual orientation minority identity. We tested psychometric properties and construct validity of a 27-item measure, the Lesbian, Gay, and Bisexual Identity Scale (LGBIS). The sample consisted of 475 adult (178 male, 237 female, 16 male-to-female, 14 female-to-male, and 30 gender queer persons) members of a special interest group, the National Coalition for Sexual Freedom. Participants completed a health needs questionnaire. Prominent findings included (1) confirmatory factor-analytic, internal consistency, and inter-correlation patterns support two LGBIS factor structures; (2) men, compared primarily to women, reported elevated scores on Acceptance Concerns, Concealment Motivation, Difficulty Process, and Negative Identity; (3) queer-identifying persons tended to report low Concealment Motivation, and high Identity Affirmation and Identity Centrality scores; (4) experimenting/fluid-identifying individuals tended toward higher Identity Uncertainty and Negative Identity, and lower Identity Centrality scores; (5) LGB community involvement was negatively associated with Concealment Motivation, Identity Uncertainty, and Negative Identity, and positively associated with Identity Superiority, Identity Affirmation, and Identity Centrality scores; and (6) Acceptance Concerns, Identity Uncertainty, and Internalized Homonegativity displayed significant positive associations with such mental health symptoms as general anxiety and posttraumatic stress. The LGBIS represents a useful approach to evaluating sexual orientation minority identity. Implications for identity theory, research, and practice are provided.

Prevalence rates, reporting, and psychosocial correlates of stalking victimization: results from a three-sample cross-sectional study.

PURPOSE: Public health and criminal justice stalking victimization data collection efforts are plagued by subjective definitions and lack of known psychosocial correlates. The present study assesses the question of stalking victimization prevalence among three groups. Psychosocial risk and protective factors associated with stalking victimization experiences were assessed. METHODS: Archival data (n = 2159) were drawn from a three-sample (i.e., U.S. nationwide sexual diversity special interest group, college student, and general population adult) cross-sectional survey of victimization, sexuality, and health. RESULTS: The range of endorsement of stalking-related victimization experiences was 13.0-47.9%. Reported perpetrators were both commonly known and unknown persons to the victim. Participants disclosed the victimization primarily to nobody or a family member/friend. Bivariate correlates of stalking victimization were female gender, Associates/Bachelor-level education, bisexual or other sexual orientation minority status, hypertension, diabetes, older age, higher weekly drug use, elevated trait aggression, higher cognitive reappraisal skills, lower rape myth acceptance, and elevated psychiatric symptoms. Logistic regression results showed the strongest factors in identifying elevated stalking victimization risk were: older age, elevated aggression, higher cognitive reappraisal skills, lesser low self-control, increased symptoms of suicidality and PTSD re-experiencing, and female and other gender minority status. CONCLUSIONS: Behavioral approaches to epidemiological and criminal justice stalking victimization are recommended. Victimization under reporting to healthcare and legal professionals were observed. Further research and prevention programming is needed to capitalize on data concerning personality and coping skills, sexual diversity, and trauma-related psychiatric symptoms.

On hate crime victimization: Rates, types, and links with suicide risk among sexual orientation minority special interest group members.

Hate crimes remain pressing traumatic events for sexual orientation minority adults. Previous literature documents patterns in which hate crime victimization is associated with elevated risk for poor mental health. The present paper held 2 aims to advance literature. First, we investigated the rates and types of hate crime victimization among sexual orientation minority adults. Second, adopting a mental health amplification risk model, we evaluated whether symptoms of depression, impulsivity, or post-traumatic stress exacerbated the hate crime victimization-suicide risk link. Participants were 521 adult sexual orientation minority-identifying members of the National Coalition for Sexual Freedom (i.e., a bondage and discipline, and sadomasochism-identifying sexuality special interest group). Participants completed demographic and mental health inventories via online administration. Results showed: (1) low rates of total lifetime hate crime victimization and (2) higher rates of interpersonal violence compared to property crime victimization within the sample. Regression results showed: (1) independent positive main effects of all 3 mental health symptom categories with suicide risk; (2) an interaction pattern in which impulsivity was positively associated with suicide risk for non-victims; and (3) an interaction pattern in which post-traumatic stress was positively associated with suicide risk for hate crime victims and non-victims. Results are discussed concerning implications for trauma-informed mental healthcare, mental health amplification models, and hate crime and suicide prevention policies.

Heritability of complex white matter diffusion traits assessed in a population isolate.

INTRODUCTION: Diffusion weighted imaging (DWI) methods can noninvasively ascertain cerebral microstructure by examining pattern and directions of water diffusion in the brain. We calculated heritability for DWI parameters in cerebral white (WM) and gray matter (GM) to study the genetic contribution to the diffusion signals across tissue boundaries. METHODS: Using Old Order Amish (OOA) population isolate with large family pedigrees and high environmental homogeneity, we compared the heritability of measures derived from three representative DWI methods targeting the corpus callosum WM and cingulate gyrus GM: diffusion tensor imaging (DTI), the permeability-diffusivity (PD) model, and the neurite orientation dispersion and density imaging (NODDI) model. These successively more complex models represent the diffusion signal modeling using one, two, and three diffusion compartments, respectively. RESULTS: We replicated the high heritability of the DTI-based fractional anisotropy (h(2) = 0.67) and radial diffusivity (h(2) = 0.72) in WM. High heritability in both WM and GM tissues were observed for the permeability-diffusivity index from the PD model (h(2) = 0.64 and 0.84), and the neurite density from the NODDI model (h(2) = 0.70 and 0.55). The orientation dispersion index from the NODDI model was only significantly heritable in GM (h(2) = 0.68). CONCLUSION: DWI measures from multicompartmental models were significantly heritable in WM and GM. DWI can offer valuable phenotypes for genetic research; and genes thus identified may reveal mechanisms contributing to mental and neurological disorders in which diffusion imaging anomalies are consistently found. Hum Brain Mapp 37:525-535, 2016. © 2015 Wiley Periodicals, Inc.

Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data.

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h(2)=0.53-0.90, p<10(-5)), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests that the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application.

Perfusion shift from white to gray matter may account for processing speed deficits in schizophrenia.

Reduced speed of cerebral information processing is a cognitive deficit associated with schizophrenia. Normal information processing speed (PS) requires intact white matter (WM) physiology to support information transfer. In a cohort of 107 subjects (47/60 patients/controls), we demonstrate that PS deficits in schizophrenia patients are explained by reduced WM integrity, which is measured using diffusion tensor imaging, mediated by the mismatch in WM/gray matter blood perfusion, and measured using arterial spin labeling. Our findings are specific to PS, and testing this hypothesis for patient-control differences in working memory produces no explanation. We demonstrate that PS deficits in schizophrenia can be explained by neurophysiological alterations in cerebral WM. Whether the disproportionately low WM integrity in schizophrenia is due to illness or secondary due to this disorder deserves further examination.

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling.

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders.

Individuals with a family history of substance use disorder (FH+) show impaired frontal white matter as indicated by diffusion tensor imaging (DTI). This impairment may be due to impaired or delayed development of myelin in frontal regions, potentially contributing to this population's increased risk for developing substance use disorders. In this study, we examined high angular resolution DTI and proton magnetic resonance spectroscopy data from the anterior corona radiata were collected in 80 FH+ and 34 FH- youths (12.9 ± 1.0 years old). White matter integrity indices included fractional anisotropy (FA), N-acetylaspartate (NAA), and total choline (tCho). Lower FA suggests decreased myelination. Decreased NAA coupled with higher tCho suggests impaired build-up and maintenance of cerebral myelin and consequently greater breakdown of cellular membranes. We found FH+ youths had lower FA (P < 0.0001) and NAA (P = 0.017) and higher tCho (P = 0.04). FH density (number of parents and grandparents with substance use disorders) was negatively correlated with FA (P < 0.0001) and NAA (P = 0.011) and positively correlated with tCho (P = 0.001). FA was independently predicted by both FH density (P = 0.006) and NAA (P = 0.002), and NAA and tCho were both independent predictors of FH density (P < 0.001). Our finding of lower frontal FA in FH+ youths corresponding to lower NAA and increased tCho is consistent with delayed or impaired development of frontal white matter in FH+ youths. Longitudinal studies are needed to determine how these differences relate to substance use outcomes.

Assessment of whole brain white matter integrity in youths and young adults with a family history of substance-use disorders.

Individuals with a family history of substance use disorders (FH+) are at a greater risk of developing substance use disorders than their peers with no such family histories (FH-) and this vulnerability is proportional to the number of affected relatives (FH density). The risk for developing substance use disorders peaks during adolescence to early adulthood in the general population, and that is thought to be related to delayed maturation of frontocortical and frontostriatal functional circuits. We hypothesized that FH+ youth and young adults have impaired myelination of frontocortical and frontostriatal white matter tracts. We examined fractional anisotropy (FA) data in 80 FH+ and 34 FH- youths (12.9 ± 1.0 years) and in 25 FH+ and 30 FH- young adults (24.3 ± 3.4 years). FH+ youths had lower FA values in both frontocortical and frontostriatal tracts as well as parietocortical tracts including the anterior, superior and posterior corona radiata and the superior frontal-occipital fasciculus. Moreover, FA values in these tracts were negatively correlated with FH density. FH+ adults had lower FA values in two frontocortical tracts: the genu of the corpus callosum and anterior corona radiata and also significant negative correlations between FA and FH density in these same tracts. In both groups, lower FA values corresponded to higher radial diffusivity suggesting reduced axonal myelination. We interpreted our findings as evidence for impaired myelination of frontal white matter that was proportional to FH density. Our data suggest that deficits may partially resolve with age, paralleling an age-related decline in risk for developing substance use disorders.

Increased forebrain activations in youths with family histories of alcohol and other substance use disorders performing a Go/NoGo task.

BACKGROUND: Youths with a family history of alcohol and other drug use disorders (FH+) are at a greater risk of developing substance use disorders than their peers with no such family histories (FH-), and this increased risk may be related to impaired maturation of forebrain circuitry. FH+ individuals have shown altered forebrain activity at rest and while performing cognitive tasks. However, it is not fully understood how forebrain activity is altered in FH+ individuals, and ultimately how these alterations may contribute to substance use disorder risk. METHODS: In this study, we tested 72 FH+ and 32 FH- youths performing a go/no-go task and examined activations in blocks with only go trials (Go Only), blocks with 50% go and 50% no-go trials (Go/NoGo), and a contrast of those 2 blocks. RESULTS: FH+ youths had significantly greater cerebral activations in both the Go and Go/NoGo blocks than FH- youths in regions including the posterior cingulate/precuneus, bilateral middle/superior temporal gyrus, and medial superior frontal gyrus with no significant group differences in the subtraction between Go Only and Go/NoGo blocks. Additionally, FH+ youths had moderately slower reaction times on go trials in the Go Only blocks. CONCLUSIONS: Our findings suggest that global activation increase in FH+ youths are modulated by FH density and are not specific to the inhibitory components of the task. This pattern of increased activations in FH+ youths may be at least partially due to impaired forebrain white matter development leading to greater activations/less efficient neural communication during task performance.

Using an innovative mixed method methodology to investigate the appropriateness of a quantitative instrument in an African context: Antiretroviral treatment and quality of life.

The relationship between quality of life (QoL) and antiretroviral treatment (ART) has mainly been studied using quantitative scales often not appropriate for use in other contexts and without taking peoples' lived experiences into consideration. Sub-Saharan Africa has the highest incidence of HIV and AIDS yet there is paucity in research done on QoL. This research report is intended to give an account of the use of a mixed method convergent parallel design as a novice approach to evaluate an instrument's context specificity, appropriateness and usefulness in another context for which it was designed. Data were collected through a qualitative exploration of the experiences of QoL of people living with HIV or AIDS (PLHA) in Africa since being on ART, as well as the quantitative measurements obtained from the HIV/AIDS-targeted quality of life (HAT-QoL) instrument. This study was conducted in three African countries. Permission and ethical approval to conduct the study were obtained. Purposive voluntary sampling was used to recruit PLHA through mediators working in community-based HIV/AIDS organisations and health clinics. Interviews were analysed through open coding and the quantitative data through descriptive statistics and the Cronbach's alpha coefficient. A much wider range and richness of experiences were expressed than measured by the HAT-QoL instrument. Although an effective instrument for use in the USA, it was found not to be sensitive, appropriate and useful in an African context in its present form. The recommendations focus on adapting the instrument using the data from the in-depth interviews or to develop a context-sensitive instrument that could measure QoL of PLHA in Africa.

Generative AI for precision neuroimaging biomarker development in psychiatry.

The explosion of generative AI offers promise for neuroimaging biomarker development in psychiatry, but effective adoption of AI methods requires clarity with respect to specific applications and challenges. These center on dataset sizes required to robustly train AI models along with feature selection that capture neural signals relevant to symptom and treatment targets. Here we discuss areas where generative AI could improve quantification of robust and reproducible brain-to-symptom associations to inform precision psychiatry applications, especially in the context of drug discovery. Finally, this communication discusses some challenges that need solutions for generative AI models to advance neuroimaging biomarkers in psychiatry.

Biomedical Data Repository Concepts and Management Principles.

The demand for open data and open science is on the rise, fueled by expectations from the scientific community, calls to increase transparency and reproducibility in research findings, and developments such as the Final Data Management and Sharing Policy from the U.S. National Institutes of Health and a memorandum on increasing public access to federally funded research, issued by the U.S. Office of Science and Technology Policy. This paper explores the pivotal role of data repositories in biomedical research and open science, emphasizing their importance in managing, preserving, and sharing research data. Our objective is to familiarize readers with the functions of data repositories, set expectations for their services, and provide an overview of methods to evaluate their capabilities. The paper serves to introduce fundamental concepts and community-based guiding principles and aims to equip researchers, repository operators, funders, and policymakers with the knowledge to select appropriate repositories for their data management and sharing needs and foster a foundation for the open sharing and preservation of research data.