Sleep-dependent engram reactivation during hippocampal memory consolidation associated with subregion-specific biosynthetic changes.

Post-learning sleep is essential for hippocampal memory processing, including contextual fear memory consolidation. We labeled context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons after fear learning. Post-learning sleep deprivation (SD) selectively disrupted reactivation of inferior blade DG engram neurons, linked to SD-induced suppression of neuronal activity in the inferior, but not superior DG blade. Subregion-specific spatial profiling of transcripts revealed that transcriptomic responses to SD differed greatly between hippocampal CA1, CA3, and DG inferior blade, superior blade, and hilus. Activity-driven transcripts, and those associated with cytoskeletal remodeling, were selectively suppressed in the inferior blade. Critically, learning-driven transcriptomic changes differed dramatically between the DG blades and were absent from all other regions. Together, these data suggest that the DG is critical for sleep-dependent memory consolidation, and that the effects of sleep loss on the hippocampus are highly subregion-specific.

Training Health Center Staff in the Provision of Culturally Responsive Care for Sexual and Gender Minority Patients: Results of a Randomized Controlled Trial.

Purpose: The study was designed to evaluate whether an educational intervention to train the health center (HC) staff to optimize care for sexual and gender minority (SGM) patients could improve documentation of sexual orientation and gender identity (SOGI) and increase preventive screenings. Methods: Twelve HCs were matched and randomized to either receive a tailored, multicomponent educational intervention or a 1-hour prerecorded webinar. Documentation of SGM status and clinical testing was measured through analysis of data that HCs report annually. Nonparametric statistics were used to assess associations between baseline HC characteristics and outcome measures. Results: The HCs were geographically, racially, and ethnically diverse. In all but one HC, <10% of the patients were identified as SGM. Intervention HCs underwent between 3 and 10 trainings, which were highly acceptable. In 2018, 9 of 12 HCs documented SO and 11 of 12 documented GI for at least 50% of their patients. Five of 6 intervention HCs increased SO documentation by 2020, compared to 3 of 6 control HCs (nonsignificant, NS). Five intervention HCs increased GI documentation, although generally by less than 10%, compared to 2 of the controls (NS). Intervention HCs tended to increase documentation of preventive services more than control HCs, but the changes were NS. Conclusions: An educational intervention designed to train the HC staff to provide culturally responsive services for SGM patients was found to be acceptable, with favorable, but nonsignificant changes. Further refinement of the intervention using a larger sample of HCs might demonstrate the effectiveness of this approach. Clinical trial registration #: NCT03554785.

HIV pre-exposure prophylaxis provision by U.S. health centers in 2021.

OBJECTIVES: The aim of this study was to assess HIV preexposure prophylaxis (PrEP) provision in U.S. health centers. DESIGN: The U.S. Ending the HIV Epidemic (EHE) initiative designated health centers as the main healthcare system through which PrEP scale-up occurs. Health centers offer primary care to over 30 million disproportionately uninsured, racially or ethnically minoritized, and low-income patients. This study is the first to assess PrEP provision across health centers, including characteristics of clinics, patient populations, and policies associated with PrEP prescribing. METHODS: The Health Resources and Services Administration's Uniform Data System contained aggregate data on PrEP prescriptions and patient sociodemographics at health centers from January 1 through December 31, 2021, in 50 U.S. states, the District of Columbia, and eight U.S. territories. We compared patient demographics and availability of Medicaid expansion and PrEP assistance programs at health centers that prescribed vs. those that did not prescribe PrEP. RESULTS: Across 1375 health centers serving 30 193 278 patients, 79 163 patients were prescribed PrEP. Health centers that prescribed any PrEP had higher proportions of sexual, gender, racial, and ethnic minority patient populations compared with health centers that prescribed no PrEP. Compared with health centers that prescribed no PrEP, a higher proportion of health centers that prescribed PrEP were located in designated high-priority jurisdictions of the EHE initiative or states with Medicaid expansion or public PrEP assistance programs. CONCLUSION: Health centers are critical for scaling up PrEP in minoritized populations disproportionately affected by HIV, facilitated through federal and state-level policies. These findings highlight service gaps and inform future interventions to optimize PrEP implementation and support EHE initiative goals.

Alcohol Use Disorder Treatment in Sexually and Gender Diverse Patients: A Retrospective Cohort Study.

Objective: While sexually and gender diverse (SGD) people have higher odds of alcohol use disorder (AUD) compared to heterosexual and cisgender people, AUD treatment access and use disparities are not well characterized. The purpose of this study is to assess differences in AUD treatment among SGD versus non-SGD populations.Methods: A retrospective cohort study was performed using data from a federally qualified health center electronic health record system in Boston, Massachusetts. Patients were 18 years or older with an International Classification of Diseases (ICD)-9 or ICD-10 AUD diagnosis and any clinic visit from January 2013 until June 2021 (N = 3,607). Treatment for AUD was identified using binary variables for medication prescription orders and visits for AUD.Results: Among patients identifying as lesbian/gay, 6.9% had an AUD diagnosis, as compared to 2.6% of patients identifying as straight/heterosexual (P < .001). The prevalence of AUD was higher in the gender diverse group as compared to the cisgender group (5.5% vs 4.4%, P < .001). There were no significant differences in receipt of a prescription for injectable naltrexone, acamprosate, or disulfiram between SGD and non-SGD patients. For oral naltrexone, 16.1% of sexually diverse patients received a prescription, as compared to 9.8% of straight/heterosexual patients (P < .001). For visits, both the straight/heterosexual cohort and the cisgender cohorts had the lowest proportion of AUD-related pharmacotherapy and individual psychotherapy visits, as compared to SGD cohorts.Conclusions: SGD patients had higher proportions of AUD diagnosis and AUD care utilization through behavioral health as compared to non-SGD patients.

Correction: Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults.

[This corrects the article DOI: 10.1371/journal.pone.0261039.].

Sexual Orientation and Gender Identity Data Completeness at US Federally Qualified Health Centers, 2020 and 2021.

Objectives. To assess the performance of US federally qualified health centers (FQHCs) after 6 years of required sexual orientation and gender identity (SOGI) data reporting and update estimated proportions of sexual and gender minorities cared for at FQHCs. Methods. We conducted secondary analyses of data reported to the 2020 and 2021 Uniform Data System from 1297 FQHCs caring for nearly 30 000 000 patients annually. We used multivariable logistic regression to explore FQHC-level and patient-level factors associated with SOGI data completeness. Results. SOGI data were missing for 29.1% and 24.0% of patients, respectively. Among patients with reported SOGI data, 3.5% identified as sexual minorities and 1.5% identified as gender minorities. Southern FQHCs and those caring for more low-income and Black patients were more likely to have above-average SOGI data completeness. Larger FQHCs were more likely to have below-average SOGI data completeness. Conclusions. Substantial increases in SOGI data completeness at FQHCs over 6 years reflect the success of reporting mandates. Future research is needed to identify other patient-level and FQHC-level factors contributing to residual levels of SOGI data missingness. (Am J Public Health. 2023;113(8):883-892. https://doi.org/10.2105/AJPH.2023.307323).

Age of Realization and Disclosure of Gender Identity Among Transgender Adults.

PURPOSE: The "rapid-onset gender dysphoria" (ROGD) hypothesis theorized, based on a parent-report survey, a distinct and more transient form of gender dysphoria in which individuals purportedly come to understand themselves as transgender and/or gender diverse (TGD) suddenly during adolescence. This study evaluated components of ROGD by (1) estimating the prevalence among TGD adults of first realizing one's TGD identity after childhood (i.e., after the onset of puberty), and (2) assessing the median time between realizing one's gender identity and disclosing this to someone else. METHODS: We conducted a secondary analysis of the 2015 US Transgender Survey, a survey of 27,715 TGD adults in the United States. Participants were asked the age at which they first realized their gender identity was different than societal expectations based on their sex assigned at birth and grouped by "childhood realization" (ages ≤ 10 years) and "later realization" (ages > 10). They were also asked the age at which they first shared their gender identity with another person. RESULTS: Of 27,497 participants, 40.8% reported "later realization" of TGD identities. Within the "childhood realization" group, the median age of sharing one's gender identity with another person was 20. In this group, the median time between realization of one's gender identity and sharing this with another person was 14 years. DISCUSSION: A substantial proportion of TGD adults reported realizing their gender identity was different from societal expectations based on their sex assigned at birth during adolescence or later. Several years typically elapsed between participants' TGD identity realization and sharing this with another person. The results of this study do not support the ROGD hypothesis.

Validation of an administrative algorithm for transgender and gender diverse persons against self-report data in electronic health records.

OBJECTIVE: To adapt and validate an algorithm to ascertain transgender and gender diverse (TGD) patients within electronic health record (EHR) data. METHODS: Using a previously unvalidated algorithm of identifying TGD persons within administrative claims data in a multistep, hierarchical process, we validated this algorithm in an EHR data set with self-reported gender identity. RESULTS: Within an EHR data set of 52 746 adults with self-reported gender identity (gold standard) a previously unvalidated algorithm to identify TGD persons via TGD-related diagnosis and procedure codes, and gender-affirming hormone therapy prescription data had a sensitivity of 87.3% (95% confidence interval [CI] 86.4-88.2), specificity of 98.7% (95% CI 98.6-98.8), positive predictive value (PPV) of 88.7% (95% CI 87.9-89.4), and negative predictive value (NPV) of 98.5% (95% CI 98.4-98.6). The area under the curve (AUC) was 0.930 (95% CI 0.925-0.935). Steps to further categorize patients as presumably TGD men versus women based on prescription data performed well: sensitivity of 97.6%, specificity of 92.7%, PPV of 93.2%, and NPV of 97.4%. The AUC was 0.95 (95% CI 0.94-0.96). CONCLUSIONS: In the absence of self-reported gender identity data, an algorithm to identify TGD patients in administrative data using TGD-related diagnosis and procedure codes, and gender-affirming hormone prescriptions performs well.

Androgenetic alopecia incidence in transgender and gender diverse populations: A retrospective comparative cohort study.

BACKGROUND: Androgenetic alopecia (AGA) is a significant challenge for many transgender and gender diverse (TGD) patients, but the rate of AGA among TGD patients receiving gender-affirming hormone therapy (GAHT) compared to cisgender patients has not yet been studied on a large scale. OBJECTIVE: We examined the incidence of AGA among TGD patients receiving GAHT compared to cisgender patients. METHODS: Retrospective cohort study using electronic health records from 37,826 patients seen at Fenway Health between August 1, 2014, and August 1, 2020. Crude and adjusted incidence rate ratios (aIRR) for AGA were calculated using Poisson regression. RESULTS: TGD patients receiving masculinizing GAHT had aIRR 2.50, 95% CI 1.71-3.65 and 1.30, 95% CI 0.91-1.86 compared to cisgender women and cisgender men, respectively. The rate of AGA for TGD patients receiving feminizing GAHT was not significantly different compared to cisgender men but was significantly increased compared to cisgender women (aIRR 1.91, 95% CI 1.25-2.92). LIMITATIONS: Inability to determine causation and limited generalizability. CONCLUSION: TGD patients receiving masculinizing GAHT have 2.5 times the rate of AGA compared to cisgender women, whereas TGD patients on feminizing GAHT did not have a significantly increased rate of AGA compared to cisgender men.

Suicidal Ideation Disparities Among Transgender and Gender Diverse Compared to Cisgender Community Health Patients.

BACKGROUND: Transgender and gender diverse (TGD) individuals experience more severe psychological distress and may be at higher risk for suicide compared to cisgender individuals. The existing literature largely consists of small-sample studies that do not assess subgroup differences. OBJECTIVE: To examine rates of self-reported suicidal ideation among four TGD groups compared to cisgender individuals. DESIGN: Data were extracted from the electronic health records of patients receiving primary care at a community health center specializing in sexual and gender minority health. A logistic regression was used to examine the relationship between sociodemographic variables and the presence of current suicidal ideation. PARTICIPANTS: 29,988 patients receiving care at a community health center in Northeastern US between 2015 and 2018. MAIN MEASURES: Demographic questionnaire, 9-item Patient Health Questionnaire KEY RESULTS: Younger age, sexual and gender minority identity, and public/grants-based insurance were associated with significantly higher odds of suicidal ideation. Relative to cisgender men, transgender men (OR=2.08; 95% CI=1.29-3.36; p=.003), transgender women (OR=3.08; 95% CI=2.05-4.63; p<.001), nonbinary (NB) individuals assigned male at birth (AMAB; OR=3.55; 95% CI=1.86-6.77; p<001), and NB individuals assigned female at birth (AFAB; OR=2.49; 95% CI=1.52-4.07; p<001) all endorsed significantly higher odds of current suicidal ideation, controlling for age, race, ethnicity, sexual orientation, and insurance status. Larger proportions of transgender women (23.6%) and NB AMAB individuals (26.7%) reported suicidal ideation not only compared to cisgender men (6.1%) and women (6.6%), but also compared to transgender men (17.4%; χ2[5, n=25,959]=906.454, p<0.001). CONCLUSIONS: TGD patients were at significantly increased risk of suicidal ideation, even after accounting for age, race, ethnicity, sexual orientation, and insurance status. Findings suggest distinct risk profiles by assigned sex at birth. Consistent assessment of and intervention for suicidal ideation should be prioritized in settings that serve TGD patients.

Sex Assigned at Birth Ratio Among Transgender and Gender Diverse Adolescents in the United States.

OBJECTIVE: Representatives of some pediatric gender clinics have reported an increase in transgender and gender diverse (TGD) adolescents presenting for care who were assigned female sex at birth (AFAB) relative to those assigned male sex at birth (AMAB). These data have been used to suggest that youth come to identify as TGD because of "social contagion," with the underlying assumption that AFAB youth are uniquely vulnerable to this hypothesized phenomenon. Reported changes in the AMAB:AFAB ratio have been cited in recent legislative debates regarding the criminalization of gender-affirming medical care. Our objective was to examine the AMAB:AFAB ratio among United States TGD adolescents in a larger and more representative sample than past clinic-recruited samples. METHODS: Using the 2017 and 2019 Youth Risk Behavior Survey across 16 states that collected gender identity data, we calculated the AMAB:AFAB ratio for each year. We also examined the rates of bullying victimization and suicidality among TGD youth compared with their cisgender peers. RESULTS: The analysis included 91 937 adolescents in 2017 and 105 437 adolescents in 2019. In 2017, 2161 (2.4%) participants identified as TGD, with an AMAB:AFAB ratio of 1.5:1. In 2019, 1640 (1.6%) participants identified as TGD, with an AMAB:AFAB ratio of 1.2:1. Rates of bullying victimization and suicidality were higher among TGD youth when compared with their cisgender peers. CONCLUSION: The sex assigned at birth ratio of TGD adolescents in the United States does not appear to favor AFAB adolescents and should not be used to argue against the provision of gender-affirming medical care for TGD adolescents.

Wide Variability in Documentation of Sexual Orientation, Gender Identity, and Preventive Health Screenings in a Diverse Sample of U.S. Community Health Centers.

Purpose: This study was conducted to characterize documentation of sexual orientation and gender identity (SOGI) and provision of screening and preventive services in a diverse sample of community health centers (CHCs). Methods: Twelve CHCs provided data submitted to the Health Resources and Services Administration (HRSA) in 2018 from their Uniform Data System (UDS) reports. Prevalence of SOGI documentation, screenings, and preventive services were calculated. Sociodemographic correlates of documentation were analyzed using Fisher's exact test and Wilcoxon rank sum/Mann-Whitney U test. Results: Patient data recording sexual orientation (SO) were missing in 2%-93% of UDS reports from the 12 CHCs, and gender identity (GI) data were missing from 0% to 96% of UDS reports. CHCs were most likely to report body mass index and tobacco screening and least likely to report hepatitis A or B vaccination, independent of SO or GI. Transgender females were less likely to have mammography documented than cisgender females. Transgender males were less likely to have anal Pap tests, be vaccinated for hepatitis B, or be referred for risky alcohol use compared to cisgender males. Patients who identified as "another gender" were less likely to be referred for risky alcohol use, undergo mammography or anal Pap testing, or receive hepatitis A vaccination than cisgender people. Individuals who did not disclose their GI were less likely to be vaccinated for hepatitis A or B than cisgender people. Conclusion: SOGI status was often not documented by a diverse array of CHCs. However, when SOGI status was documented, we saw evidence of disparities in preventive interventions and referrals, particularly for transgender patients. Clinical trial registration number: NCT03554785.

Differential Virulence Contributions of the Efflux Transporter MexAB-OprM in Pseudomonas syringae Infecting a Variety of Host Plants.

Efflux transporters such as MexAB-OprM contribute to bacterial resistance to diverse antimicrobial compounds. Here, we show that MexB contributes to epiphytic and late-stage apoplastic growth of Pseudomonas syringae strain B728a, as well as lesion formation in common bean (Phaseolus vulgaris). Although a ∆mexB mutant formed fewer lesions after topical application to common bean, these lesions contain the same number of cells (105 to 107 cells) as those caused by the wild-type strain. The internalized population size of both the wild-type and the ∆mexB mutant within small samples of surface-sterilized asymptomatic portions of leaves varied from undetectably low to as high as 105 cells/cm2. Localized bacterial populations within individual lesions consistently exceeded 105 cells/cm2. Strain B728a was capable of moderate to extensive apoplastic growth in diverse host plants, including lima bean (P. lunatus), fava bean (Vicia faba), pepper (Capsicum annuum), Nicotiana benthamiana, sunflower (Helianthus annuus), and tomato (Solanum lycopersicum), but MexB was not required for growth in a subset of these plant species. A model is proposed that MexB provides resistance to as-yet-unidentified antimicrobials that differ between plant species. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Developing and deploying an integrated workshop curriculum teaching computational skills for reproducible research.

Inspired by well-established material and pedagogy provided by The Carpentries (Wilson, 2016), we developed a two-day workshop curriculum that teaches introductory R programming for managing, analyzing, plotting and reporting data using packages from the tidyverse (Wickham et al., 2019), the Unix shell, version control with git, and GitHub. While the official Software Carpentry curriculum is comprehensive, we found that it contains too much content for a two-day workshop. We also felt that the independent nature of the lessons left learners confused about how to integrate the newly acquired programming skills in their own work. Thus, we developed a new curriculum that aims to teach novices how to implement reproducible research principles in their own data analysis. The curriculum integrates live coding lessons with individual-level and group-based practice exercises, and also serves as a succinct resource that learners can reference both during and after the workshop. Moreover, it lowers the entry barrier for new instructors as they do not have to develop their own teaching materials or sift through extensive content. We developed this curriculum during a two-day sprint, successfully used it to host a two-day virtual workshop with almost 40 participants, and updated the material based on instructor and learner feedback. We hope that our new curriculum will prove useful to future instructors interested in teaching workshops with similar learning objectives.

Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults.

OBJECTIVE: To examine associations between recalled access to gender-affirming hormones (GAH) during adolescence and mental health outcomes among transgender adults in the U.S. METHODS: We conducted a secondary analysis of the 2015 U.S. Transgender Survey, a cross-sectional non-probability sample of 27,715 transgender adults in the U.S. Using multivariable logistic regression adjusting for potential confounders, we examined associations between access to GAH during early adolescence (age 14-15), late adolescence (age 16-17), or adulthood (age ≥18) and adult mental health outcomes, with participants who desired but never accessed GAH as the reference group. RESULTS: 21,598 participants (77.9%) reported ever desiring GAH. Of these, 8,860 (41.0%) never accessed GAH, 119 (0.6%) accessed GAH in early adolescence, 362 (1.7%) accessed GAH in late adolescence, and 12,257 (56.8%) accessed GAH in adulthood. After adjusting for potential confounders, accessing GAH during early adolescence (aOR = 0.4, 95% CI = 0.2-0.6, p < .0001), late adolescence (aOR = 0.5, 95% CI = 0.4-0.7, p < .0001), or adulthood (aOR = 0.8, 95% CI = 0.7-0.8, p < .0001) was associated with lower odds of past-year suicidal ideation when compared to desiring but never accessing GAH. In post hoc analyses, access to GAH during adolescence (ages 14-17) was associated with lower odds of past-year suicidal ideation (aOR = 0.7, 95% CI = 0.6-0.9, p = .0007) when compared to accessing GAH during adulthood. CONCLUSION: Access to GAH during adolescence and adulthood is associated with favorable mental health outcomes compared to desiring but not accessing GAH.

Patterns of E-Cigarette Use Among Primary Care Patients at an Urban Community Center.

Tobacco use remains the leading cause of preventable disease and death in the US. The number of tobacco products has grown over the past decade. E-cigarette use has increased rapidly in recent years, but patterns and correlates of use have not been thoroughly assessed. We examined relationships among demographic factors, e-cigarette and conventional cigarette use in a large sample (N = 12,409) of adult patients at a community health center in the Northeastern US. Overall, 13% (N = 1675) of the sample reported ever using e-cigarettes. In logistic regression models, ever having used e-cigarettes was associated with younger age (ages 18-25; OR = 3.5, p < 0.001). Being transgender (OR = 1.8, p < 0.001), bisexual (OR = 1.5, p < 0.001), un-partnered (OR = 1.5, p < 0.001), having a lower income (OR = 1.6, p < 0.001) or a high BMI (OR = 1.4, p = 0.009) were associated with increased odds of use, whereas being a woman (OR = 0.7, p < 0.001) or Black/African American (OR = 0.7, p = 0.007) were associated with lower odds of use. Of the participants who reported e-cigarette use, a majority also endorsed current or former use of conventional cigarettes. Individuals who formerly used conventional cigarettes were nearly three times more likely to report daily e-cigarette use than current users. Among primary care patients at a community health center, e-cigarette use was reported by a sizeable portion of the sample. Overall, odds of use were higher in certain patient populations, and individuals who formally used cigarettes were more likely to report e-cigarette use than individuals who currently smoke, suggesting that e-cigarettes may be functioning as a cessation aid or a strategy to reduce conventional cigarette use.