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BACKGROUND: Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol). METHODS: We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children's Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome. RESULTS: A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants. CONCLUSIONS: In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).
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Identidad de Género , Hormonas Esteroides Gonadales , Funcionamiento Psicosocial , Personas Transgénero , Adolescente , Niño , Femenino , Humanos , Estudios Prospectivos , Testosterona/uso terapéutico , Personas Transgénero/psicología , Estradiol , Hormonas Esteroides Gonadales/uso terapéutico , Adulto Joven , MasculinoRESUMEN
PURPOSE: Mixed gonadal dysgenesis is a difference of sex development that is often confused with other conditions. Individuals have a 45,X/46,XY karyotype. Gonads are characterized by a streak gonad and a dysgenetic testis at varying levels of descent. Persistent Müllerian structures are typical (eg, hemi-uterus). There is significant phenotypic heterogeneity of the internal and external genitalia that, together with different interpretations of the definition, have contributed to a poor understanding of the condition among pediatric urologists. Mixed gonadal dysgenesis is one manifestation of the 45,X/46,XY karyotype. 45,X/46,XY mosaicism can also be associated with typical female or male external genitalia. This review aims to clarify the mixed gonadal dysgenesis definition and to provide urologists with diagnostic and management considerations for affected individuals. MATERIALS AND METHODS: We searched 3 medical databases for articles related to mixed gonadal dysgenesis. Two hundred eighty-seven full-text abstracts and manuscripts were reviewed for content pertinent to: (1) clarifying the definition of mixed gonadal dysgenesis, and (2) describing the following related to the care of affected individuals: prenatal and neonatal evaluation and management, genital surgery, gonadal malignancy risk and management, fertility, gender dysphoria/incongruence, puberty and long-term outcomes, systemic comorbidities, and transitional care. RESULTS: Fifty articles were included. Key points and implications for each of the above topics were summarized. CONCLUSIONS: Mixed gonadal dysgenesis exists on a wide phenotypic spectrum and management considerations reflect this heterogeneity. Care for individuals with mixed gonadal dysgenesis is complex, and decisions should be made in a multidisciplinary setting with psychological support.
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In brief: Transgender and gender diverse (TGD) youth demonstrate low utilization of fertility preservation before medical and surgical gender-affirming interventions. However, a significant number of TGD youth have goals for parenthood and/or recognize that their attitude toward future family-building goals may change over time. In this narrative review, we conclude that TGD young people should have ongoing opportunities to discuss their family-building goals and options for fertility preservation. Validated decision tools can help facilitate these discussions. Abstract: The number of transgender and gender diverse (TGD) youth seeking care continues to increase, necessitating comprehensive counseling about potential long-term effects of gender-affirming medical interventions on fertility. The objective of this narrative review was to examine fertility-related knowledge, attitudes, and decision-making (including factors influencing decisions, decision regret, and decision tools) among TGD youth. We searched PubMed, PsycInfo, and Google Scholar for original, peer-reviewed research investigating TGD youth attitudes and knowledge of fertility and fertility preservation, perspectives on fertility counseling and fertility preservation decision-making, as well as fertility-related decision tools. We reviewed 106 studies; eight were included in this narrative review. Four studies assessed TGD youth knowledge and attitudes of fertility and fertility preservation, three examined perspectives on fertility counseling and fertility preservation decision-making, and three discussed development of decision tools. Key findings were that: (1) many TGD youth are aware of potential fertility-related impacts of gender-affirming treatments, but there are still unmet informational needs, (2) some TGD youth report an interest in future biological parenthood, and of those who are not currently interested in biological parenthood, many acknowledge their desires may change over time, (3) ongoing discussions about fertility and fertility preservation are critical, and (4) decision tools are in development. In conclusion, TGD youth and their caregivers should receive ongoing, comprehensive fertility counseling and decision tools may be helpful to facilitate these discussions and decisions in each youth's gender-affirming care journey.
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Toma de Decisiones , Preservación de la Fertilidad , Conocimientos, Actitudes y Práctica en Salud , Salud Reproductiva , Personas Transgénero , Humanos , Preservación de la Fertilidad/psicología , Preservación de la Fertilidad/métodos , Adolescente , Personas Transgénero/psicología , Femenino , Masculino , Fertilidad , ConsejoRESUMEN
OBJECTIVE: To develop a patient- and family-centered Aid For Fertility-Related Medical Decisions (AFFRMED) interactive website targeted for transgender and nonbinary (TNB) youth/young adults and their parents to facilitate shared decision-making about fertility preservation interventions through user-centered participatory design. METHOD: TNB youth/young adults interested in or currently receiving pubertal suppression or gender-affirming hormone treatment and parents of eligible TNB youth/young adults were recruited to participate in a series of iterative human-centered co-design sessions to develop an initial AFFRMED prototype. Subsequently, TNB youth/young adults and parents of TNB youth/young adults were recruited for usability testing interviews, involving measures of usability (i.e., After Scenario Questionnaire, Net Promotor Score, System Usability Scale). RESULTS: Twenty-seven participants completed 18 iterative co-design sessions and provided feedback on 10 versions of AFFRMED (16 TNB youth/young adults and 11 parents). Nine TNB youth/young adults and six parents completed individual usability testing interviews. Overall, participants rated AFFRMED highly on measures of acceptability, appropriateness, usability, and satisfaction. However, scores varied by treatment cohort, with TNB youth interested in or currently receiving pubertal suppression treatment reporting the lowest usability scores. CONCLUSIONS: We co-created a youth- and family-centered fertility decision aid prototype that provides education and decision support in an online, interactive format. Future directions include testing the efficacy of the decision aid in improving fertility and fertility preservation knowledge, decisional self-efficacy, and decision satisfaction.
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OBJECTIVE: Differences of sex development (DSD) can affect the physical health, appearance, and psychosocial functioning of affected individuals, but little is known about how subjective appearance perceptions (body image) impact psychosocial outcomes. This study evaluated body image and its associations with psychosocial outcomes including quality of life, resilience, and psychosocial adjustment. METHODS: This cross-sectional, multi-method study assessed body image and psychosocial outcomes including quality of life, adjustment, and resilience in 97 youth and young adults with DSD (mean age = 17 ± 3.7 years; 56% assigned female in infancy) using psychometrically sound instruments. A subsample (n = 40) completed qualitative interviews. RESULTS: Quantitative results indicated that overall, participants were satisfied with their physical appearance, although less so with their primary sex characteristics. Body image dissatisfaction was associated with poorer psychosocial adjustment, quality of life, and resilience. Qualitatively, youth and young adults reported a variety of perceptions, both positive and negative, related to their body image and the impact of living with a DSD condition. Themes identified included appearance management; effects of DSD on body image; diagnostic factors and features; attitudes about diagnosis; and treatment. CONCLUSIONS: Body image is significantly associated with psychosocial outcomes in youth and young adults with DSD, with qualitative findings highlighting both positive and negative body image experiences. Results have implications for clinical care including screening for appearance concerns, normalization of appearance variations, and intervention development to better support healthy body image and psychosocial functioning in youth and young adults with DSD.
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Imagen Corporal , Trastornos del Desarrollo Sexual , Calidad de Vida , Humanos , Femenino , Masculino , Imagen Corporal/psicología , Calidad de Vida/psicología , Adolescente , Adulto Joven , Estudios Transversales , Trastornos del Desarrollo Sexual/psicología , Adulto , Resiliencia Psicológica , Funcionamiento PsicosocialRESUMEN
PURPOSE: To determine the occult nodal disease rate and whether elective regional lymph node dissection (RLND) confers any 10-year overall survival (OS) in cN0 intermediate-grade mucoepidermoid carcinoma (MEC) of the parotid gland. MATERIALS & METHODS: The National Cancer Database was reviewed from 2004 to 2016 on adults with cT1-4aN0M0 intermediate-grade parotid MEC undergoing resection with/without RLND. Comparisons between patients with and without RLND were made. Occult nodal rate and 10-year overall survival (OS) were determined. RESULTS: Out of 898 included patients with cN0 intermediate grade parotid MEC undergoing elective RLND, the occult nodal rate was 7.6%. This was significantly different from low-grade (3.9%) and high-grade (25.7%) cN0 disease. When stratified by pT-classification, marginal differences were identified between low-grade and intermediate-grade tumors, whereas high-grade tumors demonstrated increased occult nodal disease with low T-stage (pT1-pT2, 20.4% vs. 5.1%) and high T-stage (pT3-pT4a, 32.1% vs. 17.6%). Patients undergoing elective RLND were more often treated at an academic facility (53.8% vs. 41.2%), had higher pT3-pT4 tumors (19.2% vs. 10.4%), and more frequently underwent total/radical parotidectomy (46.0% vs. 29.9%) with adjuvant radiation therapy (53.8% vs. 41.0%) Cox-proportional hazard modeling did not identify RLND, regardless if stratified by nodal yield or pT-classification, nor nodal positivity as significant predictors of 10-year OS. CONCLUSIONS: The occult nodal disease in intermediate-grade parotid MEC is low and similar to low-grade. Elective RLND may have a limited impact on OS, though its effect on locoregional control remains unknown. LEVEL OF EVIDENCE: III.
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Carcinoma Mucoepidermoide , Procedimientos Quirúrgicos Electivos , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Neoplasias de la Parótida , Humanos , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/cirugía , Carcinoma Mucoepidermoide/mortalidad , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/cirugía , Neoplasias de la Parótida/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Clasificación del Tumor , Anciano , Tasa de Supervivencia , Metástasis Linfática , Glándula Parótida/cirugía , Glándula Parótida/patología , Estudios Retrospectivos , Bases de Datos FactualesRESUMEN
OBJECTIVES: Prenatal diagnoses of differences of sex development (DSD) are increasing due to availability of cell-free DNA screening (cell-free DNA screening (cfDNA)). This study explores first-hand experiences of parents whose children had prenatal findings of DSD. METHODS: Eligible parents were identified through chart review at a pediatric center and interviewed about their prenatal evaluation, decision making, informational sources, and support systems. Interviews were coded using a combined inductive and deductive thematic analysis. Parents also completed quantitative measures of decisional regret. RESULTS: Seventeen parents (13 mothers; 4 fathers) of 13 children (with 7 DSD diagnoses) were recruited. Four children had discordance between sex predicted by cfDNA versus prenatal ultrasound, and 2 had non-binary appearing (atypical) genitalia on prenatal ultrasound. Of these 6, 3 were not offered additional prenatal testing or counseling. Most parents described tension between obtaining support through disclosure of their child's diagnosis and preserving their child's autonomy/privacy, highlighting the need for mental health support. CONCLUSION: This is the first study to gather qualitative data from parents whose children had prenatal findings of DSD. We identified multiple targets for intervention to improve care for patients with DSD across the lifespan, including improvements in clinician education, pre- and post-test counseling, and patient education materials.
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Ácidos Nucleicos Libres de Células , Padres , Niño , Consejo , Emociones , Femenino , Humanos , Padres/psicología , Embarazo , Investigación CualitativaRESUMEN
Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand EF. Yet, factors associated with transgender youth EF are unknown. We investigate hypothesized predictors of EF: over-represented conditions among transgender youth (anxiety and depression symptoms, autism spectrum disorder [ASD]) and gender-affirming care. One-hundred twenty-four transgender 11-21-year-olds participated. Parents/caregivers completed EF and mental health report measures. ASD diagnostics and gender-affirming medication histories were collected. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Membership in the gender-affirming hormone treatment group was associated with better EF. ASD, anxiety symptoms, and membership in the long-duration pubertal suppression group were associated with poorer EF. Given the importance of EF skills for multiple outcomes, and the unique and additional EF demands specific to transgender youths' experiences, EF skill monitoring-and when appropriate, supports-should be considered for transgender youth.
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Trastorno del Espectro Autista , Personas Transgénero , Adolescente , Ansiedad/tratamiento farmacológico , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/psicología , Función Ejecutiva , Hormonas , Humanos , Personas Transgénero/psicologíaRESUMEN
Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements.
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Proteínas Asociadas a CRISPR/metabolismo , Proteínas Portadoras/genética , Elementos de Facilitación Genéticos/genética , Ingeniería Genética , Mutagénesis/genética , Proteínas Nucleares/genética , Animales , Secuencia de Bases , Sistemas CRISPR-Cas/genética , Células Cultivadas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Proteínas de Unión al ADN , Eritroblastos/metabolismo , Hemoglobina Fetal/genética , Genoma/genética , Humanos , Ratones , Datos de Secuencia Molecular , Especificidad de Órganos , ARN Guía de Kinetoplastida/genética , Proteínas Represoras , Reproducibilidad de los Resultados , Especificidad de la EspecieRESUMEN
PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.
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Supervivientes de Cáncer , Preservación de la Fertilidad/tendencias , Fertilidad/fisiología , Neoplasias/epidemiología , Femenino , Preservación de la Fertilidad/legislación & jurisprudencia , Humanos , Masculino , Neoplasias/patología , Neoplasias/terapia , Calidad de VidaRESUMEN
ABSTRACT: Mastectomy for chest masculinization is a commonly performed gender-affirming surgery in minor patients, a vulnerable population with unique developmental and psychosocial needs. We aimed to use principles of medical ethics (eg, autonomy, beneficence, nonmaleficence, and justice) as a framework to analyze preoperative clinical decision making by pediatric plastic surgeons who work with transmasculine and nonbinary adolescents designated female at birth presenting for chest masculinization. Two patients were selected for inclusion in this case series based on the senior author's (J.F.C.) clinical experience. A retrospective chart review was conducted to extract relevant psychosocial and clinical information from clinic notes and supplemental documentation (eg, letters from outside providers) available in the electronic medical record. In case A, a 17-year-old patient presented to a plastic surgery clinic with mixed parental support and restrictive insurance requirements. In case B, a 16-year-old patient presented to the emergency room after an attempt to remove his own breasts. The cases highlight the role of the plastic surgeon in advocating for adolescent autonomy and justice by facilitating shared family decision making and navigating barriers to care. In addition, we recommend multidisciplinary care, including trusted, transcompetent mental health professionals, to ensure beneficence and nonmaleficence by providing timely care when appropriate.
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Neoplasias de la Mama , Adolescente , Beneficencia , Niño , Femenino , Humanos , Recién Nacido , Mastectomía , Menores , Autonomía Personal , Estudios RetrospectivosRESUMEN
PURPOSE: The medical terminology applied to differences/disorders of sex development has been viewed negatively by some affected individuals. A clinical population of patients with differences/disorders of sex development and their caregivers were surveyed regarding current nomenclature, hypothesizing that those unaffiliated with support groups would have more favorable attitudes. MATERIALS AND METHODS: We recruited English and Spanish speaking patients 13 years old or older with differences/disorders of sex development and their caregivers at 5 national tertiary care clinics from July 2016 to December 2018. No diagnoses were excluded. Participants completed a survey rating terminology commonly applied to differences/disorders of sex development. Responses were compared between subgroups, including members vs nonmembers of a support group. RESULTS: Of 185 potential participants approached 133 completed the survey (72% response rate). Congenital adrenal hyperplasia (33%) was the most common diagnosis. "Variation of sex development" was the most liked term (37%) but was not liked more significantly than "disorders of sex development" (27%, p=0.16). No term was liked by a majority of respondents. "Disorders of sex development" (37%) and "intersex" (53%) were the only terms most frequently viewed unfavorably. Support group members were significantly more likely to dislike the term "intersex" (p=0.02) and to like "variation of sex development" (p=0.02). CONCLUSIONS: A clinical population of patients and their caregivers had generally neutral attitudes toward nomenclature applied to differences/disorders of sex development. Members of a support group had clearer terminology preferences. "Variation of sex development" was the most liked term, and "disorders of sex development" and "intersex" were the most disliked. No term was liked by most respondents, and no clear alternative to the present nomenclature was identified.
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Actitud Frente a la Salud , Cuidadores/psicología , Trastornos del Desarrollo Sexual , Pacientes/psicología , Terminología como Asunto , Adolescente , Estudios Transversales , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To present a topical review of minority stressors contributing to psychosocial and physical health disparities in transgender and gender expansive (TGE) adolescents. METHODS: We conducted a topical review of original research studies focused on distal stressors (e.g., discrimination; victimization; rejection; nonaffirmation), proximal stressors (e.g., expected rejection; identity concealment; internalized transphobia), and resilience factors (e.g., community connectedness; pride; parental support) and mental and physical health outcomes. RESULTS: Extant literature suggests that TGE adolescents experience a host of gender minority stressors and are at heightened risk for negative health outcomes; however, limited research has directly applied the gender minority stress framework to the experiences of TGE adolescents. Most research to date has focused on distal minority stressors and single path models to negative health outcomes, which do not account for the complex interplay between chronic minority stress, individual resilience factors, and health outcomes. Research examining proximal stressors and resilience factors is particularly scarce. CONCLUSIONS: The gender minority stress model is a helpful framework for understanding how minority stressors contribute to health disparities and poor health outcomes among TGE adolescents. Future research should include multiple path models that examine relations between gender minority stressors, resilience factors, and health outcomes in large, nationally representative samples of TGE adolescents. Clinically, adaptations of evidence-based interventions to account for gender minority stressors may increase effectiveness of interventions for TGE adolescents and reduce health disparities in this population of vulnerable youth.
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Minorías Sexuales y de Género , Personas Transgénero , Adolescente , Identidad de Género , Humanos , Grupos Minoritarios , Estrés Psicológico/epidemiologíaRESUMEN
OBJECTIVE: Discrepancies between cfDNA and ultrasound predicted fetal sex occur, possibly indicating disorders/differences of sex development (DSDs). Among expectant/recent parents, this study assessed cfDNA knowledge/use, fetal sex determination attitudes/behaviors, general knowledge of DSD, and possible psychological impact of discrepancy between fetal sex on cfDNA and ultrasound. METHOD: Parents were surveyed about fetal sex determination methods, knowledge of cfDNA and DSD, distress related to possible cfDNA inaccuracy. RESULTS: Of 916 respondents, 44% were aware of possible discrepancy between cfDNA and ultrasound, 22% were aware of DSD. 78% and 75% would be upset and worried, respectively, with results showing fetal sex discrepancy. Most (67%) revealed predicted fetal sex before delivery. 38% were offered cfDNA. Of those revealing fetal sex, 24% used cfDNA results, 71% ultrasound, and 7% both. cfDNA users were more frequently aware of possible discrepancy between cfDNA and ultrasound (76% vs 41%, P < .0001), but not of DSD (29% vs 23%, P = .29). CONCLUSION: Fetal sex determination is favored, and cfDNA is frequently used for predicting fetal chromosomal sex. Many parents are unaware of possible discrepancies between cfDNA and ultrasound, and potential for DSD. Most would be distressed by discordant results. Accurate counseling regarding limitations cfDNA for fetal sex determination is needed.
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Trastornos del Desarrollo Sexual/diagnóstico , Conocimientos, Actitudes y Práctica en Salud , Pruebas Prenatales no Invasivas , Análisis para Determinación del Sexo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ácidos Nucleicos Libres de Células/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices. Approximately 60% of previously reported RBC trait loci generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy number variant, we identified an Amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant. We further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid progenitor cells. Together, these results reinforce the importance of genetic study of diverse ancestral populations, in particular Hispanics/Latinos.
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Proteínas de Homeodominio/genética , Complejo de la Endopetidasa Proteasomal/genética , ARN Largo no Codificante/genética , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , Proteínas Supresoras de Tumor/genética , Globinas alfa/genética , Recuento de Eritrocitos , Eritrocitos , Femenino , Estudio de Asociación del Genoma Completo , Hemoglobinas/genética , Hispánicos o Latinos/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Globinas beta/genéticaRESUMEN
PURPOSE: No educational and decision support tools exist to aid transgender and non-binary (TNB) adolescents and young adults (AYA) in making decisions about fertility preservation in the context of initiating gender-affirming medical care that can impair fertility. This study identified critical content areas and learning objectives to include in a decision aid about fertility preservation targeted for TNB AYA. METHODS: Delphi methodology was leveraged to engage 80 multidisciplinary experts in reproductive medicine and pediatric transgender health care in a two round consensus building procedure. Proposed content areas rated as "probably keep" or "definitely keep" by 75% of experts were retained. Proposed learning objectives reaching 75% agreement on ratings of importance and priority were also identified. RESULTS: The Delphi procedure identified five priority content areas (Basic Reproduction; Gender-Affirming Medical Interventions: Impacts on Fertility; Established Fertility Preservation Options; Benefits and Risks of Established Fertility Preservation Procedures; Alternative Pathways to Parenting) and 25 learning objectives to prioritize in a fertility-related decision aid for TNB AYA. CONCLUSION: A multidisciplinary panel of experts achieved agreement around content areas and learning objectives to incorporate into a decision aid about fertility preservation for TNB AYA.
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Toma de Decisiones , Fertilidad/fisiología , Reproducción/fisiología , Personas Transgénero/educación , Adolescente , Técnicas de Apoyo para la Decisión , Femenino , Fertilidad/genética , Preservación de la Fertilidad/psicología , Humanos , Masculino , Personas Transgénero/psicología , Adulto JovenRESUMEN
Gene editing technologies offer new options for developing novel biomedical research models and for gene and stem cell based therapies. However, applications in many species demand high efficiencies, specificity, and a thorough understanding of likely editing outcomes. To date, overall efficiencies, rates of off-targeting and degree of genetic mosaicism have not been well-characterized for most species, limiting our ability to optimize methods. As a model gene for measuring these parameters of the CRISPR/Cas9 application in a primate species (rhesus monkey), we selected the ß-hemoglobin gene (HBB), which also has high relevance to the potential application of gene editing and stem-cell technologies for treating human disease. Our data demonstrate an ability to achieve a high efficiency of gene editing in rhesus monkey zygotes, with no detected off-target effects at selected off-target loci. Considerable genetic mosaicism and variation in the fraction of embryonic cells bearing targeted alleles are observed, and the timing of editing events is revealed using a new model. The uses of Cas9-WT protein combined with optimized concentrations of sgRNAs are two likely areas for further refinement to enhance efficiency while limiting unfavorable outcomes that can be exceedingly costly for application of gene editing in primate species.
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Hemoglobina Fetal/genética , Globinas beta/genética , Alelos , Animales , Secuencia de Bases , Sistemas CRISPR-Cas , Caspasa 9/administración & dosificación , Caspasa 9/genética , Femenino , Edición Génica/métodos , Macaca mulatta , Microinyecciones , Mosaicismo/embriología , Embarazo , ARN Mensajero/administración & dosificaciónRESUMEN
PURPOSE: To examine provider perceptions of practice behaviors and barriers related to fertility counseling, fertility preservation, and family building among transgender patients. METHODS: Participants were medical and mental health professionals who treat adult and youth transgender patients. Recruitment occurred online and in person, via professional listservs for transgender professionals, conferences, and gender clinics. From August-November 2017, 110 participants representing nine countries responded to four open-ended questions included on a survey related to provider practice behaviors and perceived barriers to fertility counseling, fertility preservation, and family building with transgender patients. Thematic coding analysis was used to identify themes. RESULTS: Multiple themes were identified including the following: access and cost issues; urgency for gender-affirming treatment; patient maturity and inability to make future-oriented decisions; and provider-related challenges pertaining to knowledge, role, and general lack of information in the nascent field of transgender reproductive health. CONCLUSION(S): This study yielded insights into practice behaviors, challenges, and perceived barriers to fertility counseling with transgender individuals and can serve as a basis for intervention development to optimize clinical practices with this population.