Adolescent neurocognitive development and decision-making abilities regarding gender-affirming care.

Recently, politicians and legislative bodies have cited neurodevelopmental literature to argue that brain immaturity undermines decision-making regarding gender-affirming care (GAC) in youth. Here, we review this literature as it applies to adolescents' ability to make decisions regarding GAC. The research shows that while adolescence is a time of peak risk-taking behavior that may lead to impulsive decisions, neurocognitive systems supporting adult-level decisions are available given deliberative processes that minimize influence of short-term rewards and peers. Since GAC decisions occur over an extended period and with support from adult caregivers and clinicians, adolescents can engage adult-level decision-making in this context. We also weigh the benefits of providing GAC access during adolescence and consider the significant costs of blocking or delaying GAC. Transgender and non-binary (TNB) adolescents face significant mental health challenges, many of which are mitigated by GAC access. Further, initiating the GAC process during adolescence, which we define as beginning at pubertal onset, leads to better long-term mental health outcomes than waiting until adulthood. Taken together, existing research indicates that many adolescents can make informed decisions regarding gender-affirming care, and that this care is critical for the well-being of TNB youth. We highlight relevant considerations for policy makers, researchers, and clinicians.

Gender Nonconformity and Minority Stress Among Lesbian, Gay, and Bisexual Individuals: A Meta-Analytic Review.

Lesbian, gay, and bisexual (LGB) individuals are less healthy than heterosexual individuals, and minority stress endured by LGB individuals contributes to these health disparities. However, within-groups differences in minority stress experiences among LGB individuals remain underexplored. Individuals are more likely to be categorized as LGB if they exhibit gender nonconformity, so gender nonconformity could influence concealability of sexual orientation among LGB individuals, carrying important implications for the visibility of their stigmatized sexual orientation identity and for how they experience and cope with minority stress. Through a meta-analytic review, we examined how gender nonconformity was associated with minority stress experiences among LGB individuals. Thirty-seven eligible studies were identified and included in analyses. Results indicate gender nonconformity is associated with experiencing more prejudice events, less concealment of sexual orientation, lower internalized homonegativity, and higher expectations of rejection related to sexual orientation among LGB individuals. Gender nonconformity is more strongly associated with experiencing prejudice events among gay and bisexual men than among lesbian and bisexual women. Gender nonconformity is systematically associated with minority stress experiences among LGB individuals, and future research must measure and examine gender nonconformity when investigating the role of minority stress in degraded health outcomes among LGB populations.

Intersectional Differences in Protective School Assets by Sexuality, Gender, Race/Ethnicity, and Socioeconomic Status.

BACKGROUND: School assets-such as connectedness, caring relationships with adults, high behavioral expectations from adults, and meaningful participation-are associated with positive outcomes for adolescents. However, little is known about how school assets differ among adolescents with intersecting marginalized identities. METHODS: We used the 2013-2014 California Healthy Kids Survey (N = 320,462 students) to examine differences in school assets with respect to sexuality, gender, race/ethnicity, and socioeconomic status using adjusted multilevel linear regression models. RESULTS: Sexual minority, gender minority, racial/ethnic minority, and low socioeconomic status adolescents had significantly lower protective school assets. For all outcomes, the differences between sexual minority and heterosexual adolescents were more pronounced among nontransgender girls than nontransgender boys; however, these differences were not consistently present among racial/ethnic minority students. For school connectedness and meaningful participation, differences for racial/ethnic minorities versus white adolescents were more pronounced among nontransgender girls than nontransgender boys. Differences between transgender adolescents and nontransgender boys were more pronounced for white adolescents compared to some other racial/ethnic minority students. Overall, adolescents with certain multiple marginalized identities had lower school assets. CONCLUSIONS: Interventions are needed to strengthen school assets among marginalized students, thereby helping mitigate health and education inequities.

Development and Psychometric Analysis of the Transgender Family Acceptance To Empowerment (TransFATE) Scale.

PURPOSE: Parent and caregiver support can reduce health disparities experienced by gender diverse youth (GDY). Parent and caregiver empowerment improves health outcomes for children with medical and mental health diagnoses, but no existing scale measures this construct in families of GDY. We aimed to develop a scale measuring empowerment in parents and caregivers of GDY. METHODS: We adapted two existing scales and added investigator-derived items to create a survey instrument. We revised using input from focus groups and experts assessing face and content validity. Using the revised scale, we surveyed parents and caregivers of GDY from across the U.S. to assess the construct validity through exploratory and confirmatory factor analyses, internal consistency, and convergent validity. RESULTS: The initial 67 items were reduced to 42 items after face and content validity analyses. Parents and caregivers (n = 309) from 31 states completed the revised measure. Most participants were white (81.4%), mothers (69.3%), and parenting a gender diverse child who identifies on the binary (transmasculine, male, transfeminine, or female; 91.3%). Exploratory factor analyses showed a two-factor solution: Factor 1 having 10 items (Cronbach's alpha = .86) and Factor 2 having six items (Cronbach's alpha = .86). Our confirmatory factor analysis demonstrated good fit (Comparative Factor Index = .972, Tucker-Lewis Index = .968, Root Mean Square Error of Approximation = .060 [90% confidence interval = .410-.078], and Standardized Root Mean Square Residual = .062). CONCLUSIONS: The Transgender Family Acceptance To Empowerment (TransFATE) scale demonstrates face, content, and construct validity among a geographically diverse sample of GDY's parents and caregivers. This scale has the potential to aid in developing and evaluating programs focused on building stronger social supports for GDY through increased family empowerment.

Social Media Use and Monitoring for Adolescents With Depression and Implications for the COVID-19 Pandemic: Qualitative Study of Parent and Child Perspectives.

BACKGROUND: Although youth report many positive experiences with social media (SM) use in their daily lives, adolescents with depression are more vulnerable to the risks of SM use than adolescents without depression. Parents protect adolescents with depression from the risks of SM use by monitoring their child's SM activity; however, this comes into conflict with the adolescent's need for autonomy in their web-based communication. The implications of SM use and monitoring for adolescents with depression and their parents are of particular relevance to the COVID-19 pandemic, as rates of SM use have increased in response to physical distancing measures. OBJECTIVE: This study aims to explore parent and child perspectives regarding the use and function of SM in the daily lives of adolescents with depression and parents' perceptions of and experience with monitoring their child's SM use. METHODS: We conducted qualitative interviews with adolescents with depression (n=23) and one parent of each adolescent (n=23) between July 2013 and September 2014. The adolescents were patients seeking treatment for depression in Pittsburgh, Pennsylvania. Data analysis included dyadic analysis of the adolescents' and parents' perspectives and qualitative descriptions of individual parent interviews to explore their experiences with SM use and monitoring. The construct of parental knowledge and factors hypothesized to contribute to parental knowledge, including adolescent disclosure, parental solicitation, and parental control, were used to guide the codebook and dyadic data analysis. RESULTS: Dyadic analyses showed that parents and their children disagreed on the use and function of SM in the daily lives of adolescents with depression, with adolescents viewing SM as a forum for honest expression of their emotions, whereas parents felt that their children's posts were inconsequential and interfered with the adolescents' lives. Furthermore, parents reported using a wide range of strategies to gain knowledge of their child's SM use to monitor their safety on SM, including direct solicitation and indirect solicitation, such as keeping the child's passwords, asking friends or siblings about their child's SM use, and restricting SM behavior and access to devices. CONCLUSIONS: Clinicians should support adolescents with depression and their parents in finding common ground for an effective and acceptable monitoring approach. Resources are provided for clinicians navigating conversations about SM use and monitoring with adolescents with depression and their parents during the COVID-19 pandemic.

Gendered Body Mass Index Percentile Charts and Transgender Youth: Making the Case to Change Charts.

Body mass index (BMI) is defined as weight (kg)/height2 (m2). Differences in BMI percentiles between sexes confound the diagnosis of weight-related disorders in transgender youth because choosing the appropriate chart is challenging. Data on BMI measures are needed for transgender youth, but there are no guidelines on how to collect or report this data. We use two theoretical cases to assert that health care providers and researchers should consider use of both male and female growth charts for transgender youth, particularly for individuals at the extremes of weight.

Early Effects of Testosterone Initiation on Body Mass Index in Transmasculine Adolescents.

PURPOSE: Increasing numbers of transgender youth are receiving hormone therapy in accordance with national and international guidelines. This study sought to determine the effect of testosterone on body mass index (BMI) z-score in transmasculine adolescents at 6 and 12 months after initiation. METHODS: A retrospective chart review collected anthropomorphic data on transmasculine adolescents, aged 13 to 19 years, before and during testosterone use. These measurements were used to create a linear mixed model to explore the change in BMI z-score after initiating testosterone. RESULTS: The increase in BMI z-score in transmasculine adolescents was significantly higher after six months of testosterone use, but there was no significant change between baseline and 12 months. CONCLUSIONS: Additional study is needed to understand the full short- and long-term impact of testosterone use on BMI z-score in transmasculine adolescents to provide appropriate informed consent and develop interventions to improve health outcomes.

Fertility Preservation Outcomes in Adolescent and Young Adult Feminizing Transgender Patients.

BACKGROUND: Fertility preservation enables patients undergoing gonadotoxic therapies to retain the potential for biological children and now has broader implications in the care of transgender individuals. Multiple medical societies recommend counseling on fertility preservation before initiating therapy for gender dysphoria; however, outcome data pre- and posttreatment are limited in feminizing transgender adolescents and young adults. METHODS: The University of Pittsburgh Institutional Research Board approved this study. Data were collected retrospectively on transgender patients seeking fertility preservation between 2015 and 2018, including age at initial consultation and semen analysis parameters. RESULTS: Eleven feminizing transgender patients accepted a referral for fertility preservation during this time; consultation occurred at median age 19 (range 16-24 years). Ten patients attempted and completed at least 1 semen collection. Eight patients cryopreserved semen before initiating treatment. Of those patients, all exhibited low morphology with otherwise normal median semen analysis parameters. In 1 patient who discontinued leuprolide acetate to attempt fertility preservation, transient azoospermia of 5 months' duration was demonstrated with subsequent recovery of spermatogenesis. In a patient who had previously been treated with spironolactone and estradiol, semen analysis revealed persistent azoospermia for the 4 months leading up to orchiectomy after discontinuation of both medications. CONCLUSIONS: Semen cryopreservation is a viable method of fertility preservation in adolescent and young adult transgender individuals and can be considered in patients who have already initiated therapy for gender dysphoria. Further research is needed to determine the optimal length of time these therapies should be discontinued to facilitate successful semen cryopreservation.

Improving the Evaluation and Management of Abnormal Uterine Bleeding in Female Adolescents Presenting for Emergency Care.

STUDY OBJECTIVE: We sought to improve emergency care for adolescents with abnormal uterine bleeding (AUB) by developing a clinical effectiveness guideline (CEG) and assessing its effect on quality of care. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A stakeholder engagement group designed a CEG algorithm for emergency AUB management. Pediatric residents received CEG training and their knowledge and attitudes were assessed using pre- and post intervention surveys. International Classification of Diseases ninth and 10th revision codes identified electronic health record data for patients who presented to the pediatric emergency department for AUB 6 months before and after CEG implementation. A weighted, 20-point scoring system consisting of prioritized aspects of history, laboratory studies, and management was developed to quantify the quality of care provided. MAIN OUTCOME MEASURES: Descriptive statistics, χ2 test, Wilcoxon rank sum test, and a run chart were used for analysis. RESULTS: Pediatric residents reported higher confidence and knowledge scores post CEG implementation. Of the 91 patients identified, 62 met inclusion criteria. Median score was 14 ± 7 before CEG implementation and 15.5 ± 6 after. The Wilcoxon rank sum test showed a difference in AUB evaluation and management scores (P = .09) after implementation of the CEG. Run chart data showed no shifts or trends (overall median score, 14 points). Pre- and post implementation, points were deducted most frequently for not assessing personal/family clotting disorder history. The largest improvements in care were with appropriate medication dosing and disposition. CONCLUSION: We designed a CEG and educational intervention for AUB management in a pediatric emergency department. These findings suggest our CEG might be an effective tool to improve emergency AUB care for adolescents and could increase trainees' confidence in managing this condition, although additional cycles are needed.

Group-based trajectories of parent-child communication and parental knowledge between sexual minority and heterosexual girls and their associations with substance use.

INTRODUCTION: Sexual minority girls (SMGs) may be at high risk for substance use partially due to anti-gay discrimination. Low levels of parent-child communication and parental knowledge may contribute to this risk. This study seeks to identify parent-child communication and parental knowledge trajectories, determine the likelihood of SMGs following these trajectories, and describe the relationships between these trajectories, sexual orientation, and substance use. METHODS: This is a secondary data analysis of the Pittsburgh Girls Study (N = 2450), a longitudinal study on the changes in behaviors among girls throughout childhood. We generated group trajectory models of parentchild communication and parental knowledge starting from age 12 to age 17 years. We then tested the likelihood of SMGs belonging to these group trajectories and the association between group trajectory membership and substance use at age 18 years. RESULTS: SMGs were more likely than were heterosexual girls to follow the infrequent decreasing parent-child communication trajectory and the slowly decreasing parental knowledge trajectory and were more likely than were heterosexual girls to engage in substance use at age 18 years. Parent-child communication and parental knowledge trajectories were statistically significant mediators between sexual orientation and substance use. CONCLUSION: Frequency of parent-child communication and levels of parental knowledge may be determinants of substance use among SMGs. These results have implications for developing substance use prevention programs among sexual minority youth targeting parent-child relationships.

Trends in Parental Monitoring and Knowledge Over Time Between Sexual Minority and Heterosexual Girls.

This study assessed whether trajectories of parental monitoring components were different for sexual minority girls (SMGs) compared to heterosexual girls. We recruited 14-19-year-old girls from two adolescent medicine clinics. We estimated growth curve models to compare how components of parental monitoring-adolescent disclosure, parental solicitation, and parental knowledge-changed over 2 years for SMGs and heterosexual girls. SMGs and heterosexual girls had similar trajectory slopes and quadratic forms of adolescent disclosure, but SMGs had consistently lower adolescent disclosure scores. Parental knowledge trajectories indicated differential intercepts and slopes for SMGs compared to heterosexual girls, suggesting potential higher risk for maladaptive behaviors. Results of this study suggest that parental monitoring may operate differently over time for SMGs compared to heterosexual girls.

Differences in Parental Monitoring Components and Their Associated Health Indicators Between Sexual-Minority and Heterosexual Girls.

Our study sought to assess whether parental monitoring and their associations with health behaviors differed for heterosexual girls compared to sexual minority girls (girls who identified as lesbian or bisexual, endorsed same-sex attraction, or had same-sex romantic or sexualpartners). We analyzed three components of parental monitoring-adolescent disclosure, parental solicitation, and parental knowledge-between heterosexual and sexual minority girls.We also tested if the associations between these three constructs and adolescent relationship abuse, suicidality, heavy drinking, binge drinking, anxiety symptoms, and depressive symptoms were different for heterosexual girls compared to sexual minority girls. Sexual minority girls were less likely to disclose accurately to their parents their location and activities and perceived their parents asked less and knew less about their location and activities than did heterosexual girls. Heterosexual girls who reported higher levels of adolescent disclosure were less likely than were sexual minority girls to report suicidality and anxiety symptoms. Additionally, heterosexual girls who reported higher levels of parental knowledge were also less likely than were sexual minority girls to report anxiety and depressive symptoms. These findings suggest that parental monitoring may not be as protective forsexual minority girls as it is for heterosexual girls.

Predictors of screening for hyperlipidemia in an urban pediatric tertiary care center.

INTRODUCTION: It is unknown how the conflicting recommendations of the American Academy of Pediatrics and the US Preventive Services Task Force on pediatric hyperlipidemia affect screening. OBJECTIVES: (a) Identify clinical predictors for screening for hyperlipidemia, (b) assess the adherence to the 2008 American Academy of Pediatrics guidelines, and (c) determine the efficacy of reminder cards in increasing the adherence to the aforementioned guidelines. METHODS: Retrospective chart review in the resident, attending, and adolescent medicine clinics during a 3-month period. Reminder cards on each patient chart outlining guidelines for lipid screening for the same clinics were inserted and prospectively assessed for adherence during the following 3 months. RESULTS: Older age and higher body mass index increased likelihood (odds ratio = 1.2 and 12.7, respectively) for lipid screening. Reminder cards improved adherence in the resident clinic only (χ2 P = .016). CONCLUSIONS: Age and body mass index were the most significant predictors for lipid screening. Reminder cards modestly improved adherence among resident physicians.

Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung.

Urease, a major virulence factor for Cryptococcus neoformans, promotes lethal meningitis/encephalitis in mice. The effect of urease within the lung, the primary site of most invasive fungal infections, is unknown. An established model of murine infection that utilizes either urease-producing (wt and ure1::URE1) or urease-deficient (ure1) strains (H99) of C. neoformans was used to characterize fungal clearance and the resultant immune response evoked by these strains within the lung. Results indicate that mice infected with urease-producing strains of C. neoformans demonstrate a 100-fold increase in fungal burden beginning 2 weeks post-infection (as compared with mice infected with urease-deficient organisms). Infection with urease-producing C. neoformans was associated with a highly polarized T2 immune response as evidenced by increases in the following: 1) pulmonary eosinophils, 2) serum IgE levels, 3) T2 cytokines (interleukin-4, -13, and -4 to interferon-gamma ratio), and 4) alternatively activated macrophages. Furthermore, the percentage and total numbers of immature dendritic cells within the lung-associated lymph nodes was markedly increased in mice infected with urease-producing C. neoformans. Collectively, these data define cryptococcal urease as a pulmonary virulence factor that promotes immature dendritic cell accumulation and a potent, yet non-protective, T2 immune response. These findings provide new insights into mechanisms by which microbial factors contribute to the immunopathology associated with invasive fungal disease.

Elevated p21-activated kinase 2 activity results in anchorage-independent growth and resistance to anticancer drug-induced cell death.

p21-activated kinase 2 (PAK-2) seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug-induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug-induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug-induced apoptosis.