A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Women Veterans\u27 Pathways to and Perspectives on Veterans Affairs Health Care

BACKGROUND: We examined Veterans Affairs (VA) health care experiences among contemporary women veteran patients receiving care at a VA medical center. Specifically, we examined women veteran patients\u27 satisfaction with VA care along dimensions in line with patient-centered medical home (patient-aligned care teams [PACT] in VA) priorities, and pathways through which women initially accessed VA care. METHODS: We used a mixed methods research design. First, 249 racially diverse women (ages 22-64) who were past-year users of primary care at a VA medical center completed interviewer-administered surveys in 2012 assessing ratings of satisfaction with care in the past year. We then conducted in-depth qualitative interviews of a subset of women surveyed (n = 25) to gain a deeper understanding of perspectives and experiences that shaped satisfaction with care and to explore women\u27s initial pathways to VA care. RESULTS: Ratings of satisfaction with VA care were generally high, with some variation by demographic characteristics. Qualitative interviews revealed perceptions of care centered on the following themes: 1) barriers to care delay needed medical care, while innovative care models facilitate access, 2) women value communication and coordination of care, and 3) personalized context of VA care, including gender sensitive care shapes women\u27s perceptions. Pathways to VA care were characterized by initial delays, often attributable to lack of knowledge or negative perceptions of VA care. Informal social networks were instrumental in helping women to overcome barriers. CONCLUSIONS: Findings highlight convergence of women\u27s preferences with PACT priorities of timely access to care, provider communication, and coordination of care, and suggest areas for improvement. Outreach is needed to address gaps in knowledge and negative perceptions. Initiatives to enhance women veterans\u27 social networks may provide an information-sharing resource

Intimate partner violence as a predictor of substance use outcomes among women: A systematic review

Although the correlation between experience of intimate partner violence (IPV) and substance use among women has been well-established, there is no consensus on whether or how IPV impacts subsequent substance use behaviors or treatment success. To identify research gaps and implications for substance use treatment, we conducted a systematic review to identify and examine evidence on IPV as a predictor of subsequent substance use behaviors, substance use disorders (SUD), and treatment outcomes among women. We included studies published between 2010 and 2020 that assessed IPV experiences as a predictor of subsequent substance use behaviors (i.e., use initiation, increased use), SUD diagnosis, or treatment outcomes (i.e., incomplete treatment, relapse) among women. From 576 unique records, we included 10 studies (4 longitudinal, 4 cross-sectional, 2 qualitative). Alcohol use and alcohol use disorder were the most commonly studied outcomes (n = 6); findings were mixed regarding the significance of IPV being associated with subsequent alcohol outcomes. Three studies examined illicit drug use, finding that physical and sexual IPV predicted crack/cocaine use and were associated with SUD diagnoses. Four studies examining SUD treatment outcomes found IPV to impede treatment engagement and completion, increasing the likelihood of relapse. To our knowledge, this is the first systematic review of the literature on IPV as a predictor of substance use behaviors and treatment outcomes among women. Findings highlight the need for diverse SUD treatment modalities to incorporate IPV screening and referral to appropriate services into their programming to improve SUD management and the overall health and wellbeing of women

Differences in Childhood Adversity, Suicidal Ideation, and Suicide Attempt Among Veterans and Nonveterans

Adverse childhood experiences (ACEs) are robustly associated with physical and mental health problems over the life span. Relatively limited research has examined the breadth of ACEs among military veteran populations, for whom ACEs may be premilitary traumas associated with suicidal ideation and attempt. Using data from the Comparative Health Assessment Interview Research Study, a large national survey sponsored by the U.S. Department of Veterans Affairs, this investigation examined the prevalence of 22 self-reported potentially traumatic experiences before the age of 18 (i.e., ACEs) among veterans and nonveterans and estimated the association of ACEs with suicidal ideation and attempt at age 18 or older. All analyses were weighted to account for complex sampling design and stratified by gender. The study sample included 9,571 veteran men, 3,143 nonveteran men, 5,543 veteran women, and 1,364 nonveteran women. Veteran men reported greater average frequency of ACEs than nonveteran men (2.7 ACEs vs. 2.3 ACEs, respectively, p < .001); 11.1% of veteran men indicated >6 ACEs compared with 7.3% of nonveteran men (p < .001). Veteran women reported greater average frequency of ACEs than nonveteran women (3.1 ACEs vs. 2.4 ACEs, respectively, p < .001). Among women, more veterans than nonveterans reported >6 ACEs (14.9% vs. 8.6%, respectively, p < .001). The strongest correlate of suicide attempt at age 18 or older for veteran men was having >6 ACEs (adjusted odds ratio, aOR = 4.20, 95%CI = 2.72-6.49); for veteran women, the strongest correlate was suicidal ideation or attempt before age 18 (aOR = 5.37, 95%CI = 4.11-7.03). Suicide prevention research, policy, and practice should address ACEs among veterans as salient premilitary risk factors. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Impact of Social Determinants of Health on Medical Conditions Among Transgender Veterans

Introduction Transgender individuals experience pronounced disparities in health (e.g., mood disorders, suicide risk) and in the prevalence of social determinants of housing instability, financial strain, and violence. The objectives of this study were to understand the prevalence of social determinants among transgender veterans and assess their associations with medical conditions. Methods This project was a records review using administrative data from the U.S. Department of Veterans Affairs databases for 1997–2014. Transgender veterans (N=6,308) were defined as patients with any of four ICD-9 diagnosis codes associated with transgender status. Social determinants were operationalized using ICD-9 codes and Department of Veterans Affairs clinical screens indicating violence, housing instability, or financial strain. Multiple logistic regression was used to assess the associations of social determinants with medical conditions: mood disorder, post-traumatic stress disorder, alcohol abuse disorder, illicit drug abuse disorder, tobacco use disorder, suicidal risk, HIV, and hepatitis C. Results After adjusting for sociodemographic variables, housing instability and financial strain were significantly associated with all medical conditions except for HIV, and violence was significantly associated with all medical conditions except for tobacco use disorder and HIV. There was a dose response–like relationship between the increasing number of forms of social determinants being associated with increasing odds for medical conditions. Conclusions Social determinants are prevalent factors in transgender patients’ lives, exhibiting strong associations with medical conditions. Documenting social determinants in electronic health records can help providers to identify and address these factors in treatment goals