Posttraumatic Stress Disorder Symptoms and Incarceration: The Impact on Sexual Risk-Taking, Sexually Transmitted Infections, and Depression Among Black Sexual Minority Men in HIV Prevention Trials Network (HPTN) 061.

Black men and people belonging to sexual minority groups are disproportionately impacted by criminal legal involvement and sexually transmitted infections (STIs). Traumatic experiences are often associated with later criminal legal involvement, depression symptoms, sexual risk behavior, and STIs. Research on the joint influence of trauma and incarceration on STI risk among racial and/or sexual minority people is limited. This study tested the association between post-traumatic stress disorder (PTSD) symptoms and incarceration on sexual risk behavior and STI among Black sexual minority men, a population that may be at higher risk for contracting STIs. Using data from the HIV Prevention Trials Network 061 Study, a longitudinal study of adult Black sexual minority men in six U.S. cities (N = 855), we tested associations between past six-month incarceration and subsequent sexual risk behavior, STI, and depression symptoms, for those with and without pre-incarceration PTSD symptoms. PTSD symptoms were elevated among participants who reported Hispanic ethnicity, having sex with both men and women, and previous incarceration. Although there were not significant differences between recent incarceration and sexual risk for those with and without PTSD, incarceration was linked to some sexual risk behaviors regardless of PTSD symptoms. Among people with PTSD symptoms, there was a higher prevalence of sexual risk and depression symptoms, regardless of incarceration. These findings suggest a potentially compounding influence of PTSD symptoms and incarceration on sexual risk and infection among Black sexual minority men.

Reducing overdose deaths among persons with opioid use disorder in connecticut.

BACKGROUND: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary. METHODS: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons. RESULTS: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime. CONCLUSIONS: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.

Police Harassment and Psychiatric, Sexual, and Substance Use Risk Among Black Sexual Minority Men and Black Transgender Women in the HIV Prevention Trials 061 Cohort.

BACKGROUND: Black sexual minority men and Black transgender women (BSMM/BTW) experience disproportionate levels of HIV/STI-related risk factors as well as police harassment (PH). PH is linked to psychiatric risk and could play a role in substance use, sexual risk behavior, and HIV/STI risk. METHODS: We used data from the HIV Prevention Trials Network 061(HPTN 061) study to examine associations between PH and HIV/STI-related outcomes. Using PH exposure measured at baseline and 6-month study visits, we examined an ordinal exposure (PH reported at both visits, PH reported at either visit, versus PH reported at neither baseline nor 6 months) and a binary exposure of persistent PH reported at both visits (yes versus no). We estimate risk ratios (RR) for associations between PH and depression, use of alcohol and methamphetamine, multiple partnerships, condomless sex, and syphilis. RESULTS: Persistent PH (binary) was associated with a 20% or greater increase in the risk of depression (RR, 1.26 (1.07, 1.47)) and multiple partnerships (RR, 1.20 (1.05, 1.39)). There was evidence that ordinal PH was associated with elevated risk of alcohol use (RR, 1.17 (1.00, 1.36)); the point estimate for the association between persistent PH and alcohol use was similar but the imprecision was greater (RR, 1.16 (0.95, 1.42)). CONCLUSION: PH may influence not only mental health but also behavioral risks that contribute to HIV/STI among BSMM/BTW, highlighting the potential wide-ranging and downstream effects of PH on health. Further research is required to confirm associations and elucidate pathways through which PH may influence HIV/STI among BSMM/BTW.

Undiagnosed Disease Network collaborative approach in diagnosing rare disease in a patient with a mosaic CACNA1D variant.

The Undiagnosed Disease Network (UDN) is comprised of clinical and research experts collaborating to diagnose rare disease. The UDN is funded by the National Institutes of Health and includes 12 different clinical sites (About Us, 2022). Here we highlight the success of collaborative efforts within the UDN Clinical Site at Vanderbilt University Medical Center (VUMC) in utilizing a cohort of experts in bioinformatics, structural biology, and genetics specialists in diagnosing rare disease. Our UDN team identified a de novo mosaic CACNA1D variant c.2299T>C in a 5-year-old female with a history of global developmental delay, dystonia, dyskinesis, and seizures. Using a collaborative multidisciplinary approach, our VUMC UDN team diagnosed the participant with Primary Aldosteronism, Seizures, and Neurologic abnormalities (PASNA) OMIM: 615474 due to a rare mosaic CACNA1D variant (O'Neill, 2013). Interestingly, this patient was mosaic, a phenotypic trait previously unreported in PASNA cases. This report highlights the importance of a multidisciplinary approach in diagnosing rare disease.

Optimizing cultivation strategies and scaling up for fucoxanthin production using Pavlova sp.

The microalgal-based production of fucoxanthin has emerged as an imperative research endeavor due to its antioxidant, and anticancer properties. In this study, three brown marine microalgae, namely Skeletonema costatum, Chaetoceros gracilis, and Pavlova sp., were screened for fucoxanthin production. All strains displayed promising results, with Pavlova sp. exhibiting the highest fucoxanthin content (27.91 mg/g) and productivity (1.16 mg/L·day). Moreover, the influence of various cultivation parameters, such as culture media, salinity, sodium nitrate concentration, inoculum size, light intensity, and iron concentration, were investigated and optimized, resulting in a maximum fucoxanthin productivity of 7.89 mg/L·day. The investigation was further expanded to large-scale outdoor cultivation using 50 L tubular photobioreactors, illustrating the potential of Pavlova sp. and the cultivation process for future commercialization. The biomass and fucoxanthin productivity for the large-scale cultivation were 70.7 mg/L·day and 4.78 mg/L·day, respectively. Overall, the findings demonstrated considerable opportunities for fucoxanthin synthesis via microalgae cultivation and processing.

Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

Racial and ethnic inequities in substance use treatment among women with opioid use disorder.

Background: Research describes inequities in substance use treatment, but few studies focus specifically on racial and ethnic disparities in a range of aspects of substance use treatment among women with opioid use disorder (OUD).Objective: To examine whether substance use treatment (i.e. receipt, sources, barriers) differs by race and ethnicity among women with opioid use disorder (OUD) and to identify factors associated with treatment gap (i.e. needing treatment but not receiving it).Methods: We performed cross-sectional analyses using National Survey on Drug Use and Health 2015-2019 data, restricted to non-Hispanic Black, non-Hispanic White, and Hispanic women with past-year OUD (unweighted n = 1089). We estimated the prevalence of aspects of treatment among racial and ethnic groups, and used modified Poisson regression to estimate correlates of reported treatment gap.Results: Approximately 68% of White versus 87% of Black and 81% of Hispanic women with OUD had a treatment gap (p-value 0.0034). Commonly reported barriers to treatment included prioritization, affordability, and stigma. Older age was associated with lower prevalence of treatment gap among all women [prevalence ratio (PR) = 0.83, and 95% confidence interval (CI): 0.76, 0.92], while criminal legal involvement and healthcare coverage was associated with a lower prevalence of treatment gap among Hispanic and White women only (past year arrest: Hispanic women PR = 0.38, 95% CI: 0.17, 0.86; White women PR = 0.62, 95% CI: 0.47, 0.82).Conclusions: Receipt of treatment is low among women with OUD, especially Black and Hispanic women. Intersectional intervention approaches are needed to increase access and reduce inequities.

Environmental stress mediates groundwater microbial community assembly.

Community assembly describes how different ecological processes shape microbial community composition and structure. How environmental factors impact community assembly remains elusive. Here we sampled microbial communities and >200 biogeochemical variables in groundwater at the Oak Ridge Field Research Center, a former nuclear waste disposal site, and developed a theoretical framework to conceptualize the relationships between community assembly processes and environmental stresses. We found that stochastic assembly processes were critical (>60% on average) in shaping community structure, but their relative importance decreased as stress increased. Dispersal limitation and 'drift' related to random birth and death had negative correlations with stresses, whereas the selection processes leading to dissimilar communities increased with stresses, primarily related to pH, cobalt and molybdenum. Assembly mechanisms also varied greatly among different phylogenetic groups. Our findings highlight the importance of microbial dispersal limitation and environmental heterogeneity in ecosystem restoration and management.

Evaluation of self-directed specimen collection for chlamydia and gonorrhea testing among people who use drugs.

Background: People who use drugs (PWUD) often have elevated sexually transmitted infection (STI) risk and unmet healthcare needs. Self-directed STI specimen collection (i.e., individuals collect the specimen and mail to the laboratory) may be valuable in addressing STI testing barriers among PWUD. Methods: Within a cohort study among PWUD in New York City, we conducted a cross-sectional substudy from November 2021-August 2022 assessing sexual health with a one-time online survey (n = 120); participants could opt-in to receive a self-collection kit. Participants who opted-in were mailed a kit containing collection materials (males: urine cup, females: vaginal swab), pre-paid return label, instructions, and educational information. Specimens were sent to the laboratory and tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). We measured the number of kits requested, delivered, mailed to the lab, and CT/GC positive; and examined differences in requesting a kit by sociodemographic and behavioral characteristics. Results: Sixty-three total kits were requested by 44 unique participants. Of the 63 requested, 41 were delivered; one kit was undeliverable at the provided address and the rest were not sent due to no address provided or being duplicate requests. Of the 41 kits delivered, three participants returned the kit to the lab; of those, one was positive for CT and GC. The greatest differences in those who did and did not request a kit were observed by age, sexual orientation, past-year sex trade and casual partnerships, and experiences of relationship violence. Conclusions: Self-directed specimen collection may be desirable for PWUD, but research is needed to understand barriers to this testing approach for this population.

Probable digenic inheritance of Diamond-Blackfan anemia.

A 26-year-old female proband with a clinical diagnosis and consistent phenotype of Diamond-Blackfan anemia (DBA, OMIM 105650) without an identified genotype was referred to the Undiagnosed Diseases Network. DBA is classically associated with monoallelic variants that have an autosomal-dominant or -recessive mode of inheritance. Intriguingly, her case was solved by a detection of a digenic interaction between non-allelic RPS19 and RPL27 variants. This was confirmed with a machine learning structural model, co-segregation analysis, and RNA sequencing. This is the first report of DBA caused by a digenic effect of two non-allelic variants demonstrated by machine learning structural model. This case suggests that atypical phenotypic presentations of DBA may be caused by digenic inheritance in some individuals. We also conclude that a machine learning structural model can be useful in detecting digenic models of possible interactions between products encoded by alleles of different genes inherited from non-affected carrier parents that can result in DBA with an unrealized 25% recurrence risk.

Impact of Decarceration Plus Alcohol, Substance Use, and Mental Health Screening on Life Expectancies of Black Sexual Minority Men and Black Transgender Women Living With HIV in the United States: A Simulation Study Based on HPTN 061.

BACKGROUND: Given the disproportionate rates of incarceration and lower life expectancy (LE) among Black sexual minority men (BSMM) and Black transgender women (BTW) with HIV, we modeled the impact of decarceration and screening for psychiatric conditions and substance use on LE of US BSMM/BTW with HIV. METHODS: We augmented a microsimulation model previously validated to predict LE and leading causes of death in the US with estimates from the HPTN 061 cohort and the Veteran's Aging Cohort Studies. We estimated independent associations among psychiatric and substance use disorders, to simulate the influence of treatment of one condition on improvement on others. We used this augmented simulation to estimate LE for BSMM/BTW with HIV with a history of incarceration under alternative policies of decarceration (ie, reducing the fraction exposed to incarceration), screening for psychiatric conditions and substance use, or both. RESULTS: Baseline LE was 61.3 years. Reducing incarceration by 25%, 33%, 50%, and 100% increased LE by 0.29, 0.31, 0.53, and 1.08 years, respectively, versus no reductions in incarceration. When reducing incarceration by 33% and implementing screening for alcohol, tobacco, substance use, and depression, in which a positive screen triggers diagnostic assessment for all psychiatric and substance use conditions and linkage to treatment, LE increased by 1.52 years compared with no screening or decarceration. DISCUSSION: LE among BSMM/BTW with HIV is short compared with other people with HIV. Reducing incarceration and improving screening and treatment of psychiatric conditions and substance use could substantially increase LE in this population.

Associations Between Incarceration History and Risk of Hypertension and Hyperglycemia: Consideration of Differences among Black, Hispanic, Asian and White Subgroups.

BACKGROUND: Studies have shown that adults with a history of incarceration have elevated cardiovascular (CVD) risk. Research on racial/ethnic group differences in the association between incarceration and CVD risk factors of hypertension and hyperglycemia is limited. OBJECTIVE: To assess racial/ethnic group differences in the association between incarceration and hypertension and hyperglycemia. DESIGN: We performed a secondary data analysis using the National Longitudinal Survey of Adolescent to Adult Health (Add Health). Using modified Poisson regression, we estimated the associations between lifetime history of incarceration reported during early adulthood with hypertension and hyperglycemia outcomes measured in mid-adulthood, including incident diagnosis. We evaluated whether associations varied by self-reported race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and Asian). PARTICIPANTS: The analytic sample included 4,015 Add Health respondents who self-identified as non-Hispanic White, Non-Hispanic Black, Hispanic, and Asian, and provided incarceration history and outcome data. MAIN MEASURES: Outcome measures included (1) hypertension (2) systolic blood pressure ≥ 130 mmHg, and (3) hyperglycemia. KEY RESULTS: In non-Hispanic Black and non-Hispanic White participants, there was not evidence of an association between incarceration and measured health outcomes. Among Hispanic participants, incarceration was associated with hyperglycemia (Adjusted Risk Ratio (ARR): 2.1, 95% Confidence Interval (CI): 1.1-3.7), but not with hypertension risk. Incarceration was associated with elevated systolic blood pressure (ARR: 3.1, CI: 1.2-8.5) and hypertension (ARR: 1.7, CI: 1.0-2.8, p = 0.03) among Asian participants, but not with hyperglycemia risk. Incarceration was associated with incident hypertension (ARR 2.5, CI 1.2-5.3) among Asian subgroups. CONCLUSIONS: Our findings add to a growing body of evidence suggesting that incarceration may be linked to chronic disease outcomes. Race/ethnic-specific results, while limited by small sample size, highlight the need for long-term studies on incarceration's influence among distinct US groups.

Effects of error, chimera, bias, and GC content on the accuracy of amplicon sequencing.

IMPORTANCE: Amplicon sequencing of targeted genes is the predominant approach to estimate the membership and structure of microbial communities. However, accurate reconstruction of community composition is difficult due to sequencing errors, and other methodological biases and effective approaches to overcome these challenges are essential. Using a mock community of 33 phylogenetically diverse strains, this study evaluated the effect of GC content on sequencing results and tested different approaches to improve overall sequencing accuracy while characterizing the pros and cons of popular amplicon sequence data processing approaches. The sequencing results from this study can serve as a benchmarking data set for future algorithmic improvements. Furthermore, the new insights on sequencing error, chimera formation, and GC bias from this study will help enhance the quality of amplicon sequencing studies and support the development of new data analysis approaches.

Age Differences in the Associations Between Incarceration and Subsequent Substance Use, Sexual Risk-Taking, and Incident STI Among Black Sexual Minority Men and Black Transgender Women in the HIV Prevention Trials 061 Cohort.

Incarceration can lead to different risk behaviors often due to increased distress and disruption of social networks. It is not well known, however, how these associations may differ by age. In this study, we measure age differences in longitudinal associations between incarceration and substance use, sex risk, and sexually transmitted infection (STI) among Black sexual minority men and Black transgender women (BSMM/BTW). We recruited BSMM/BTW from 2009 to 2011 that were part of the HIV Prevention Trials Network 061 study. We compared those less than 30 years old (n = 375) to those 30 years old or greater (n = 794) examining substance use, sex risk, and STI infection stratified by age. Logistic regression with inverse probability weighting was used for the statistical analysis. Approximately 59% of the sample reported incarceration history. In adjusted analysis, incarceration was more strongly associated with alcohol use and stimulant use among older individuals as was sexual risk behaviors including buying and selling sex. Concurrent partnerships were associated with the younger age groups. STI incidence was associated with younger individuals while associations with HIV infection were similar for the two age groups. Understanding differences in substance use and STI risk among age cohorts is imperative to the design and implementation of re-entry programs. Younger BSMM/BTW participating in re-entry support programs may benefit in particular from HIV/STI prevention and care efforts, while post-release substance abuse treatment and harm reduction programs should target older individuals with continued substance abuse.

Child Death in a Resource-Limited Setting: A Simulation Case for Pediatric Residents to Prepare for Global Health Electives.

Introduction: Pediatric residents are increasingly pursuing global health electives. Differences in cultural norms and management around pediatric deaths in resource-limited settings can be emotionally overwhelming for residents. Educational resources are needed to better equip them for handling these stressful situations. We developed a predeparture simulation child death case to prepare pediatric residents for their global health elective. Methods: The simulation module included a clinical case followed by a multidisciplinary structured debriefing. The case featured a 5-year-old, malnourished child in hypovolemic shock who clinically deteriorates and dies. After obtaining a history and performing a physical examination, residents were expected to diagnose severe malnutrition, treat hypovolemic shock, and decide how far to extend resuscitation with the limited resources. Upon returning from abroad, residents were invited to complete a survey on the utility of the simulation case module in preparing for their elective. Results: Twenty-nine residents participated in the simulation case module, and 18 completed the survey. Seventeen agreed or strongly agreed that the simulation module was a useful tool for preparation (Mdn = 4.5 on a 5-point Likert scale). Residents reflected that the simulation module helped manage expectations and provided them with an understanding of the cross-cultural differences in managing pediatric deaths in a resource-limited setting. Discussion: Pediatric residents trained in resource-rich countries do not encounter death often. Postgraduate training programs could consider simulations like this one to prepare such residents for cross-cultural differences in managing pediatric deaths and build resiliency to operate in resource-limited settings.

A medical odyssey of a 72-year-old man with Charcot-Marie-Tooth disease type 2 newly diagnosed with biallelic variants in SORD gene causing sorbitol dehydrogenase deficiency.

A 72-year-old man was referred to the Undiagnosed Diseases Network (UDN) because of gradual progressive weakness in both lower extremities for the past 45 years. He was initially diagnosed as having Charcot-Marie-Tooth disease type 2 (CMT2) without a defined molecular genetic cause. Exome sequencing (ES) failed to detect deleterious neuromuscular variants. Very recently, biallelic variants in sorbitol dehydrogenase (SORD) were discovered to be a novel cause of inherited neuropathies including CMT2 or distal hereditary motor neuropathy (dHMN) referred to as Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy (SORDD, OMIM 618912). The most common variant identified was c.757delG; p.A253Qfs*27. Through the Vanderbilt UDN clinical site, this patient was formally diagnosed with SORDD after the identification of homozygosity for the above SORD frameshift through UDN Genome Sequencing (GS). His medical odyssey was solved by GS and detection of extremely high levels of sorbitol. The diagnosis provided him the opportunity to receive potential treatment with an investigational drug in a clinical trial for SORDD. We suggest that similar studies be considered in other individuals thought to possibly have CMT2 or dHMN.

A Tale of 8 Cities: Pediatric Critical Care Redeployment to Adult Care During Wave 1 of COVID-19.

BACKGROUND: Pediatric hospital resources including critical care faculty (intensivists) redeployed to provide care to adults in adult ICUs or repurposed PICUs during wave 1 of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: To determine the magnitude of pediatric hospital resource redeployment and the experience of pediatric intensivists who redeployed to provide critical care to adults with COVID-19. METHODS: A mixed methods study was conducted at 9 hospitals in 8 United States cities where pediatric resources were redeployed to provide care to critically ill adults with COVID-19. A survey of redeployed pediatric hospital resources and semistructured interviews of 40 redeployed pediatric intensivists were simultaneously conducted. Quantitative data were summarized as median (interquartile range) values. RESULTS: At study hospitals, there was expansion in adult ICU beds from a baseline median of 100 (86-107) to 205 (108-250). The median proportion (%) of redeployed faculty (88; 66-100), nurses (46; 10-100), respiratory therapists (48; 18-100), invasive ventilators (72; 0-100), and PICU beds (71; 0-100) was substantial. Though driven by a desire to help, faculty were challenged by unfamiliar ICU settings and culture, lack of knowledge of COVID-19 and fear of contracting it, limited supplies, exhaustion, and restricted family visitation. They recommended deliberate preparedness with interprofessional collaboration and cross-training, and establishment of a robust supply chain infrastructure for future public health emergencies and will redeploy again if asked. CONCLUSIONS: Pediatric resource redeployment was substantial and pediatric intensivists faced formidable challenges yet would readily redeploy again.

Evaluation of warning strategies to reduce faking during military recruitment.

The applicant faking literature suggests that faking warnings - brief messages that dissuade applicants from faking - can reduce faking on personality tests by up to 50%. However, the efficacy of warnings may be limited by their atheoretical construction. Further, these threatening messages can cause applicants to feel negatively about the personality test, potentially reducing their validity during the selection process. We tried to improve the efficacy of faking warnings, while minimizing negative applicant reactions, by leveraging theory from the accountability and morality literatures. We tested three new faking warnings that emphasized short-term accountability, long-term accountability, and morality. To do so, we tested 466 military trainees undergoing basic training at the Canadian Armed Forces and asked them to engage in a selection simulation. We assigned groups of trainees to the different faking warning conditions and guided them through the simulation. We found that a faking warning emphasizing short-term accountability, which threatened to detect fakers by contacting references and using "internal integrity checks," reduced applicant faking. None of the other messages had any effect when compared to a no-warning control group.

Associations between police harassment and distrust in and reduced access to healthcare among Black sexual minority men: A longitudinal analysis of HPTN 061.

OBJECTIVE: Evaluate associations between racialized and homophobia-based police harassment (RHBPH) and healthcare distrust and utilization among Black Sexual Minority Men (BSMM). METHODS: We utilized data from a longitudinal cohort study from HIV Prevention Trials Network (HPTN) 061 with baseline, six and 12 month follow-up assessments. Using multivariable analysis, we evaluated associations between RHBPH and healthcare distrust and utilization reported at the 6 and 12 month visits. RESULTS: Of 1553 BSMM present at baseline, 1160 were available at six-month follow-up. In multivariable analysis, increasing frequency of RHBPH was associated with increasing levels of distrust in healthcare providers (aOR 1.31, 95% CI: 1.00, 1.74) and missing 50% or more of healthcare visits at six-month follow-up (aOR 1.93, 95% CI: 1.09, 3.43). CONCLUSIONS: Recent experiences of RHBPH are associated with reduced trust in and access to healthcare among BSMM, with more frequent RHBPH associated with greater vulnerability.

Heterozygous rare variants in NR2F2 cause a recognizable multiple congenital anomaly syndrome with developmental delays.

Nuclear receptor subfamily 2 group F member 2 (NR2F2 or COUP-TF2) encodes a transcription factor which is expressed at high levels during mammalian development. Rare heterozygous Mendelian variants in NR2F2 were initially identified in individuals with congenital heart disease (CHD), then subsequently in cohorts of congenital diaphragmatic hernia (CDH) and 46,XX ovotesticular disorders/differences of sexual development (DSD); however, the phenotypic spectrum associated with pathogenic variants in NR2F2 remains poorly characterized. Currently, less than 40 individuals with heterozygous pathogenic variants in NR2F2 have been reported. Here, we review the clinical and molecular details of 17 previously unreported individuals with rare heterozygous NR2F2 variants, the majority of which were de novo. Clinical features were variable, including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations, thus expanding the phenotypic spectrum associated with NR2F2 variants. The variants seen were predicted loss of function, including a nonsense variant inherited from a mildly affected mosaic mother, missense and a large deletion including the NR2F2 gene. Our study presents evidence for rare, heterozygous NR2F2 variants causing a highly variable syndrome of congenital anomalies, commonly associated with heart defects, developmental delays/intellectual disability, dysmorphic features, feeding difficulties, hypotonia, and genital anomalies. Based on the new and previous cases, we provide clinical recommendations for evaluating individuals diagnosed with an NR2F2-associated disorder.