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BACKGROUND: The risk of venous thromboembolism (VTE) with gender-affirming hormone therapy (GAHT) in transgender and gender non-binary (TNB) youth is unclear. OBJECTIVE: To identify the rate of VTE in a cohort of TNB youth followed in the transgender health clinic at Boston Children's Hospital, and to investigate the impact of congenital thrombophilia diagnosis on the use of GAHT. METHODS: ICD-9 and ICD-10 codes were used to identify eligible individuals, defined as (i) having a diagnosis of gender dysphoria and (ii) venous thromboembolism (VTE). Data were abstracted from a review of medical records. A second data query assessed TNB individuals who had an associated thrombophilia diagnosis. RESULTS: The primary analysis included 1860 individuals. Total 942 individuals (50.6%) had started GAHT at the time of data analysis. Mean age (±SD) at GAHT initiation was 16.8 (±1.9) years. Five thrombotic events were identified in three (0.13%) individuals, all in the setting of additional VTE risk factors. Only two of five thrombotic events occurred while receiving GAHT. The rate of VTE in the GAHT cohort did not statistically differ from the rate of VTE in the non-GAHT cohort (0.1% vs. 0.2%, p = .62). Of the 10 individuals diagnosed with a congenital thrombophilia, two transmasculine individuals received prophylactic anticoagulation prior to GAHT. No VTE has been reported to date in this cohort. CONCLUSIONS: In our cohort, VTE was rare in the TNB youth and was not associated with GAHT use. TNB youth with congenital thrombophilia have not developed VTE in the setting of GAHT use to date.
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Despite growing diversity in the United States population, studies show that medical education lacks representation of conditions in darker skin tones. Given that medical conditions present differently in different skin tones, limited exposure to images of darker tones in medical training may contribute to incorrect or delayed diagnoses, perpetuating health inequities. This study examines the preclinical curriculum at the Georgetown University School of Medicine (GUSOM) to report on its image representation with respect to skin tone and to assess the impact of a student-driven initiative in achieving visual learning equity (VLE). Of 1050 preclinical images, 58.2% depicted conditions in light/white skin tones, 31.3% in medium/brown, and 10.5% in dark/black. The microbiology and pathology courses had the highest percentages of dark/black and medium/brown images. Infectious disease images made up 36.3% of all images with 54.6% light/white, 31.5% medium/brown, and 13.9% dark/black. Overall, the first images representing conditions were 63.5% light/white, 30.0% medium/brown, and 6.6% dark/black. When dark/black images were presented first, 64.3% were of infectious diseases, compared to 35.1% for medium/brown and only 28.4% for white/light first images that were infectious diseases. A significant increase in images of conditions in darker skin tones was observed in the IRD course 2022 compared to the IRD course 2020 (P<.001). Our study highlights an underrepresentation of darker skin tones compared to lighter skin tones in the GUSOM preclinical curriculum. A student-led initiative significantly increased the representation of darker skin tones in dermatologic images, demonstrating the potential impact of such efforts in achieving VLE in medical education.J Drugs Dermatol. 2024;23(7):519-524. doi:10.36849/JDD.7992.
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Curriculum , Dermatología , Enfermedades de la Piel , Humanos , Estudios Transversales , Dermatología/educación , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/terapia , Pigmentación de la Piel , Educación de Pregrado en Medicina/métodos , Estados Unidos , Estudiantes de Medicina/estadística & datos numéricosRESUMEN
PURPOSE: This study explored factors associated with parents' attitudes and intentions to seek information about the COVID-19 vaccine for their children (ages 0-18) and intentions to vaccinate their age-eligible children. DESIGN AND METHODS: As part of an anonymous online cross-sectional survey, parents' vaccine attitudes, COVID-19 vaccine intentions for their children, health literacy, health numeracy, and sociodemographic variables were assessed. Multivariable ordered logistic regression models identified factors associated with parents' COVID-19 vaccine intentions for their children. RESULTS: Parents/guardians (n = 963) were mostly White (82.3%), insured (88.0%), and college graduates (57.3%). Men reported higher intentions than women to seek information about the COVID-19 vaccine for their children (p = 0.003) and higher intentions to vaccinate their children (p = 0.049). Parental characteristics associated with increased intentions to have their children vaccinated included higher educational attainment (p < 0.001), more positive general vaccine attitudes (p < 0.001), preference for health information in a language other than English (p = 0.006), higher income (p = 0.048), having health insurance (p = 0.05), health literacy (p = 0.024), and health numeracy (p = 0.049). CONCLUSIONS: Multiple sociodemographic characteristics including male gender, higher health literacy and numeracy, and language preference are noteworthy factors associated with parental COVID-19 vaccine intentions that could inform the planning and implementation of educational interventions. PRACTICE IMPLICATIONS: Nurses are important sources of trusted information and play an important role in parent/family health education and in understanding myriad factors that may improve attitudes and enhance readiness toward vaccine uptake. Our findings emphasize the potential value of examining tailored/targeted COVID-19 vaccine education according to key influencing factors.
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Vacunas contra la COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Padres , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto Joven , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Estudios Transversales , Intención , Padres/psicología , Vacunación/psicología , Factores Socioeconómicos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Here we present a transgender male adolescent with an androgen receptor-positive serous borderline ovarian tumour in the setting of testosterone treatment for medical gender transition. To our knowledge, this is the second report of borderline tumour in a transgender individual and the first in an adolescent, an age group in which borderline tumours are extremely rare. We discuss the specific considerations of treating ovarian tumours in the transgender male population, the incompletely understood role of androgens in the genesis of ovarian epithelial neoplasia, and an emphasis on assessing cancer risk in transgender patients based on patient anatomy.
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Cistadenocarcinoma Seroso/patología , Neoplasias Ováricas/patología , Personas Transgénero , Adolescente , Agentes Anticonceptivos Hormonales/administración & dosificación , Cistadenocarcinoma Seroso/química , Cistadenocarcinoma Seroso/cirugía , Femenino , Humanos , Masculino , Acetato de Noretindrona/administración & dosificación , Neoplasias Ováricas/química , Neoplasias Ováricas/cirugía , Receptores Androgénicos/análisis , SalpingooforectomíaRESUMEN
Skeletal metastasis occurs in around 75% of advanced breast cancers, with the disease incurable once cancer cells disseminate to bone, but there remains an unmet need for biomarkers to identify patients at high risk of bone recurrence. This study aimed to identify such a biomarker and to assess its utility in predicting response to adjuvant zoledronic acid (zoledronate). We used quantitative proteomics (stable isotope labelling by amino acids in cell culture-mass spectrometry; SILAC-MS) to compare protein expression in a bone-homing variant (BM1) of the human breast cancer cell line MDA-MB-231 with parental non-bone-homing cells to identify novel biomarkers for risk of subsequent bone metastasis in early breast cancer. SILAC-MS showed that dedicator of cytokinesis protein 4 (DOCK4) was upregulated in bone-homing BM1 cells, confirmed by western blotting. BM1 cells also had enhanced invasive ability compared with parental cells, which could be reduced by DOCK4-shRNA. In a training tissue microarray (TMA) comprising 345 patients with early breast cancer, immunohistochemistry followed by Cox regression revealed that high DOCK4 expression correlated with histological grade (p = 0.004) but not oestrogen receptor status (p = 0.19) or lymph node involvement (p = 0.15). A clinical validation TMA used tissue samples and the clinical database from the large AZURE adjuvant study (n = 689). Adjusted Cox regression analyses showed that high DOCK4 expression in the control arm (no zoledronate) was significantly prognostic for first recurrence in bone (HR 2.13, 95%CI 1.06-4.30, p = 0.034). No corresponding association was found in patients who received zoledronate (HR 0.812, 95%CI 0.176-3.76, p = 0.790), suggesting that treatment with zoledronate may counteract the higher risk for bone relapse from high DOCK4-expressing tumours. High DOCK4 expression was not associated with metastasis to non-skeletal sites when these were assessed collectively. In conclusion, high DOCK4 in early breast cancer is significantly associated with aggressive disease and with future bone metastasis and is a potentially useful biomarker for subsequent bone metastasis risk. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Quimioterapia Adyuvante , Femenino , Proteínas Activadoras de GTPasa/genética , Técnicas de Silenciamiento del Gen/métodos , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Proteínas de Neoplasias/metabolismo , Pronóstico , Proteómica/métodos , Medición de Riesgo/métodos , Células Tumorales Cultivadas , Regulación hacia Arriba , Adulto Joven , Ácido Zoledrónico/uso terapéuticoRESUMEN
BACKGROUND: Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and access. Although the open science movement advocates unfettered access to research data, many of the UK's longitudinal cohort studies operate systems of managed data access, in which access is governed by legal and ethical agreements between stewards of research datasets and researchers wishing to make use of them. Amongst other things, these agreements aim to respect the reasonable expectations of the research participants who provided data and samples, as expressed in the consent process. Arguably, responsible data management and governance of data and sample use are foundational to the consent process in longitudinal studies and are an important source of trustworthiness in the eyes of those who contribute data to genomic and biosocial research. METHODS: This paper presents an ethnographic case study exploring the foundational principles of a governance infrastructure for Managing Ethico-social, Technical and Administrative issues in Data ACcess (METADAC), which are operationalised through a committee known as the METADAC Access Committee. METADAC governs access to phenotype, genotype and 'omic' data and samples from five UK longitudinal studies. FINDINGS: Using the example of METADAC, we argue that three key structural features are foundational for practising responsible data sharing: independence and transparency; interdisciplinarity; and participant-centric decision-making. We observe that the international research community is proactively working towards optimising the use of research data, integrating/linking these data with routine data generated by health and social care services and other administrative data services to improve the analysis, interpretation and utility of these data. The governance of these new complex data assemblages will require a range of expertise from across a number of domains and disciplines, including that of study participants. Human-mediated decision-making bodies will be central to ensuring achievable, reasoned and responsible decisions about the use of these data; the METADAC model described in this paper provides an example of how this could be realised.
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Macrodatos , Investigación Biomédica/ética , Genómica/ética , Difusión de la Información/ética , Investigación Biomédica/economía , Bases de Datos Genéticas/economía , Bases de Datos Genéticas/ética , Genotipo , HumanosRESUMEN
Increased stretch tolerance can contribute to improved range of motion (ROM). Since menthol-based topical analgesics (TopAnalg) suppress pain, they may increase stretch thresholds improving ROM. Other modalities such as transcutaneous electrical nerve stimulation and rolling have demonstrated decreased pain sensitivity in the contralateral limb. The purpose of this study was to investigate the effects of a TopAnalg on active and passive ROM of the treated and contralateral (untreated) leg. With a double blind, repeated measures design, 14 university students had a TopAnalg or a placebo gel applied to their hamstrings, rested for 20-min and then either performed static or dynamic stretching. Prior to gel application and after stretching, participants were tested for passive static, active and ballistic hip flexion ROM. Near significant greater ballistic hip flexion ROM for both legs (treated: p = 0.08; 3.6%; contralateral: p = 0.1; 1.6%) were observed with the TopAnalg. With dynamic stretching, ballistic hip flexion ROM of both limbs at post-test (p=0.01-0.007; 3.3-4.2%) and post-10 minutes (p = 0.06-0.01; 2.7-4.1%) decreased with the placebo, whereas there were no significant reductions with the TopAnalg. There was a near significant higher active hip flexion ROM (stretched leg: p = 0.05; 4.6%), and significantly higher ballistic hip flexion ROM (p = 0.04-0.05; 3.4-3.5%) with static versus dynamic stretching for both legs. In conclusion, TopAnalg can increase hip flexion ROM of the treated and contralateral limbs. Secondly, static stretching contributed to greater ballistic ROM in both the stretched and non-stretched contralateral limbs. Hence, TopAnalg may be used to enhance flexibility training with rehabilitation or highly trained athletes.
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Analgésicos/administración & dosificación , Articulación de la Cadera/fisiología , Rango del Movimiento Articular/efectos de los fármacos , Administración Tópica , Método Doble Ciego , Femenino , Músculos Isquiosurales/fisiología , Humanos , Masculino , Mentol/administración & dosificación , Ejercicios de Estiramiento Muscular , Mialgia/prevención & control , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Because no single person or group holds knowledge about all aspects of research, mechanisms are needed to support knowledge exchange and engagement. Expertise in the research setting necessarily includes scientific and methodological expertise, but also expertise gained through the experience of participating in research and/or being a recipient of research outcomes (as a patient or member of the public). Engagement is, by its nature, reciprocal and relational: the process of engaging research participants, patients, citizens and others (the many 'publics' of engagement) brings them closer to the research but also brings the research closer to them. When translating research into practice, engaging the public and other stakeholders is explicitly intended to make the outcomes of translation relevant to its constituency of users. METHODS: In practice, engagement faces numerous challenges and is often time-consuming, expensive and 'thorny' work. We explore the epistemic and ontological considerations and implications of four common critiques of engagement methodologies that contest: representativeness, communication and articulation, impacts and outcome, and democracy. The ECOUTER (Employing COnceptUal schema for policy and Translation Engagement in Research) methodology addresses problems of representation and epistemic foundationalism using a methodology that asks, "How could it be otherwise?" ECOUTER affords the possibility of engagement where spatial and temporal constraints are present, relying on saturation as a method of 'keeping open' the possible considerations that might emerge and including reflexive use of qualitative analytic methods. RESULTS: This paper describes the ECOUTER process, focusing on one worked example and detailing lessons learned from four other pilots. ECOUTER uses mind-mapping techniques to 'open up' engagement, iteratively and organically. ECOUTER aims to balance the breadth, accessibility and user-determination of the scope of engagement. An ECOUTER exercise comprises four stages: (1) engagement and knowledge exchange; (2) analysis of mindmap contributions; (3) development of a conceptual schema (i.e. a map of concepts and their relationship); and (4) feedback, refinement and development of recommendations. CONCLUSION: ECOUTER refuses fixed truths but also refuses a fixed nature. Its promise lies in its flexibility, adaptability and openness. ECOUTER will be formed and re-formed by the needs and creativity of those who use it.
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Comunicación , Participación de la Comunidad , Proyectos de Investigación , Investigación Biomédica Traslacional , HumanosRESUMEN
Precision medicine aims to fix what is wrong with today's healthcare: a lack of targeted interventions tailored to the person. It encompasses many aspects of health; chief among these is one's genetic profile. Researchers are making progress as gene-sequencing technologies get better and cheaper. Although there is cause for optimism, as several initiatives at Sunnybrook Research Institute show, scientific, systemic, and logistical challenges must be surmounted before advances can be integrated into the clinic. Despite these barriers, precision medicine is the only way forward.
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Atención a la Salud/métodos , Genómica , Medicina de Precisión/tendencias , HumanosRESUMEN
Context: Treatment for transmasculine youth (TMY) can involve testosterone treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHas can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY. Objective: Our objective was to determine how GnRHa treatment before testosterone impacts FAH. Methods: Retrospective cohort study at 5 US transgender health clinics. Participants were 32 TMY treated with GnRHas in early to midpuberty before testosterone (GnRHa + T group) and 62 late/postpubertal TMY treated with testosterone only (T-only group). Results: The difference between FAH minus midparental target height (MPTH) was +2.3 ± 5.7â cm and -2.2 ± 5.6â cm in the GnRHa + T and T-only groups, respectively (P < .01). In the GnRHa + T group, FAH was 1.8 ± 3.4â cm greater than predicted adult height (PAH) (P < .05) and FAH vs initial height (IH) z-score was 0.5 ± 1.2 vs 0.16 ± 1.0 (P < .05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59â cm (95% CI 0.31, 0.9â cm), stage 3 breast development at start of GnRHa was associated with 6.5â cm lower FAH compared with stage 2 (95% CI -10.43, -2.55), and FAH was 7.95â cm greater in the GnRHa + T group than in T-only group (95% CI -10.85, -5.06). Conclusion: Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/postpuberty. TMY considering GnRHas should be counseled that GnRHas may mildly increase their FAH if started early.
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Context: Access to gender-affirming medical care is associated with better mental health outcomes in transgender and gender diverse youth. In 2021 and 2022, legislation aiming to ban gender-affirming medical care for youth was proposed in 24 states. Objective: This study aimed to (1) assess the impact of this legislation on pediatric providers based on legislative status of their state of practice and (2) identify the themes of concerns reported by them. Methods: A mixed-methods study was conducted via an anonymous survey distributed to pediatric endocrinology providers. Survey responses were stratified based on US state of practice, with attention to whether legislation aiming to ban gender-affirming care had been considered. Data were analyzed both quantitatively and qualitatively. Results: Of 223 respondents, 125 (56.0%) were currently providing gender-affirming medical care. A total of 103 (45.7%) respondents practiced in a state where legislation aiming to ban gender-affirming care had been proposed and/or passed between January 2021 to June 2022. Practicing in legislation-affected states was associated with negative experiences for providers including (1) institutional pressure that would limit the ability to provide care, (2) threats to personal safety, (3) concerns about legal action being taken against them, (4) concerns about their career, and (5) institutional concerns about engagement with media. Major qualitative themes emerging for providers in legislation-affected states included safety concerns and the impact of laws on medical practice. Conclusion: This study suggests that legislation aiming to ban health care for transgender youth may decrease access to qualified providers in affected states.
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Objective: While the field of pediatric endocrinology, and the American Board of Pediatrics, continues expanding training to include gender-affirming care, many pediatric endocrinology fellowship programs do not have formal curriculum for this patient population. Members of the Pediatric Endocrine Society (PES) that have a special interest in transgender health designed a curriculum based on Endocrine Society practice guidelines to expand the knowledge of gender affirming care for medical trainees' and faculty. Methods: PES members designed a 5-part self-guided educational module series with embedded knowledge questions. Uniquely, medical ethical reflections were included within each module. Participants completed baseline demographic and baseline and follow-up knowledge surveys. Results: Most participants were pediatric endocrinology fellows and 44 % percent (n = 21) completed all study components, including the follow up knowledge survey. Knowledge question data analysis demonstrated knowledge gained in medical management of pubertal youth and surgical interventions. Conclusion: This is the first medical education curriculum in gender-affirming care created by pediatric endocrinologists grounded in the Endocrine Society practice guidelines. This study demonstrates medical knowledge gained in caring for gender diverse youth and is the first to incorporate ethical considerations for this patient population. While initially designed for pediatric endocrinology trainees and faculty, this curriculum may be of great utility for any provider interested in caring for gender diverse youth.
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CONTEXT: Loss-of-function mutations in the maternally imprinted genes, MKRN3 and DLK1, are associated with central precocious puberty (CPP). Mutations in MKRN3 are the most common known genetic etiology of CPP. OBJECTIVE: This work aimed to screen patients with CPP for MKRN3 and DLK1 mutations and analyze the effects of identified mutations on protein function in vitro. METHODS: Participants included 84 unrelated children with CPP (79 girls, 5 boys) and, when available, their first-degree relatives. Five academic medical institutions participated. Sanger sequencing of MKRN3 and DLK1 5' upstream flanking and coding regions was performed on DNA extracted from peripheral blood leukocytes. Western blot analysis was performed to assess protein ubiquitination profiles. RESULTS: Eight heterozygous MKRN3 mutations were identified in 9 unrelated girls with CPP. Five are novel missense mutations, 2 were previously identified in patients with CPP, and 1 is a frameshift variant not previously associated with CPP. No pathogenic variants were identified in DLK1. Girls with MKRN3 mutations had an earlier age of initial pubertal signs and higher basal serum luteinizing hormone and follicle-stimulating hormone compared to girls with CPP without MRKN3 mutations. Western blot analysis revealed that compared to wild-type MKRN3, mutations within the RING finger domain reduced ubiquitination whereas the mutations outside this domain increased ubiquitination. CONCLUSION: MKRN3 mutations were present in 10.7% of our CPP cohort, consistent with previous studies. The novel identified mutations in different domains of MKRN3 revealed different patterns of ubiquitination, suggesting distinct molecular mechanisms by which the loss of MRKN3 results in early pubertal onset.
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Mutación Missense , Pubertad Precoz , Niño , Masculino , Femenino , Humanos , Pubertad Precoz/genética , Ubiquitina-Proteína Ligasas/genética , Mutación , Ubiquitinación , PubertadRESUMEN
Transgender and gender diverse (TGD) youth are at risk of worsened health disparities during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Health care delivery by pediatric endocrinologists, including rapid implementation of telemedicine services, during the pandemic has not been documented. The Pediatric Endocrine Society's Transgender Health Special Interest Group met virtually to survey practice patterns during the SARS-CoV-2 pandemic. The majority of pediatric endocrinologists continued to provide most aspects of medical transition; however, we also identified several barriers to care. Overall, the survey results demonstrated that telemedicine can be utilized as an effective way to provide gender-affirming medical care to TGD youth.
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Makorin ring finger protein 3 (MKRN3) is an important neuroendocrine player in the control of pubertal timing and upstream inhibitor of gonadotropin-releasing hormone secretion. In mice, expression of Mkrn3 in the hypothalamic arcuate and anteroventral periventricular nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if the persistence of hypothalamic Mkrn3 expression peripubertally would result in delayed puberty. Female mice that received neonatal bilateral intracerebroventricular injections of a recombinant adeno-associated virus expressing Mkrn3 had delayed vaginal opening and first estrus compared with animals injected with control virus. Subsequent estrous cycles and fertility were normal. Interestingly, male mice treated similarly did not exhibit delayed puberty onset. Kiss1, Tac2, and Pdyn mRNA levels were increased in the mediobasal hypothalamus in females at postnatal day 28, whereas kisspeptin and neurokinin B protein levels in the arcuate nucleus were decreased, following Mkrn3 overexpression, compared to controls. Cumulatively, these data suggest that Mkrn3 may directly or indirectly target neuropeptides of Kiss1 neurons to degradation pathways. This mouse model suggests that MKRN3 may be a potential contributor to delayed onset of puberty, in addition to its well-established roles in central precocious puberty and the timing of menarche.
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Hipotálamo , Maduración Sexual , Ubiquitina-Proteína Ligasas , Animales , Femenino , Hormona Liberadora de Gonadotropina , Hipotálamo/metabolismo , Kisspeptinas/genética , Masculino , Ratones , Neuroquinina B/genética , Maduración Sexual/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Clinicians of all disciplines, including pediatric endocrinologists, are likely to encounter transgender and gender-diverse (TGD) young people in their practice regardless of whether they specialize in gender-affirming medical care. Because of this, it is important to be aware of the ways in which medical professionals can affirm these individuals. Although gender-affirming therapy should always include affirmation including proper use of names and pronouns, the transition journey will look different for each patient. The gender-affirming care of TGD young people may include both medical and nonmedical interventions (e.g., social transition). Therapies utilized for medical gender transition such as gonadotropin-releasing hormone agonists and/or gender-affirming hormones have implications for growth, bone health, cardiovascular health, and fertility, although these impacts are not yet completely understood. This review provides an overview of the care of transgender young people as well as a summary of what is known about the outcomes of these therapies. Clinicians should advise TGD young people and their families of the known and unknown risks and work together with patients to decide upon a treatment and follow-up regimen that aligns with their individual gender affirmation and health goals.
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Personas Transgénero , Niño , Humanos , Adolescente , HormonasRESUMEN
ADAMs (a disintegrin and metalloproteinase) are a family of type I transmembrane glycoproteins related to snake venom metalloproteases and disintegrins. They are regulatory proteins that modulate intercellular adhesion and the bioavailability of growth factors, and have been implicated in many disease states, including cancer, immunity and inflammation. One member of the ADAM family, ADAM28, has been reported to bind to the integrin α4ß1 in humans; however, the distribution of ADAM28 and the biological consequences of ADAM28-α4ß1 interactions are yet to be fully elucidated. The expression of ADAM28 in human and murine tissues was examined by multiple Affymetrix microarray analyses, real-time RT-PCR (reverse transcription-PCR) and immunohistochemical staining. We found that ADAM28 has a relatively restricted expression pattern in mouse and human and is highly expressed in the B-lymphocyte lineage, including chronic lymphocytic leukaemic B-cells. The murine B-lymphoma line L1-2 and recombinant soluble murine ADAM28 were used to investigate ADAM28-α4ß1 interactions. Our data reveal that ADAM28 binding to α4ß1 is typical of integrin-ligand interactions, since it is attenuated by anti-functional integrin antibodies, and is enhanced by Mn2+ and the integrin mAb (monoclonal antibody) 9EG7. However, a key finding was that soluble ADAM28 unexpectedly enhanced α4ß1-dependent cell adhesion to VCAM-1 (vascular cell adhesion molecule-1). In so doing ADAM28 was able to influence lymphocyte adhesion to, and migration through, endothelial monolayers, suggesting a physiological role for ADAM28 in regulating the specific spatial and temporal transendothelial migration of lymphocytes.
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Proteínas ADAM/metabolismo , Linfocitos B/citología , Integrina alfa4beta1/metabolismo , Migración Transendotelial y Transepitelial , Proteínas ADAM/genética , Proteínas ADAM/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Linfocitos B/inmunología , Células COS , Adhesión Celular , Linaje de la Célula , Chlorocebus aethiops , Humanos , Manganeso/metabolismo , Ratones , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
The sexually dimorphic trait of height is one aspect of the experience of transgender and gender-diverse (TGD) individuals that may influence their gender dysphoria and satisfaction with their transition. In this article, we have reviewed the current knowledge of the factors that contribute to one's final adult height and how it might be affected in TGD youth who have not experienced their gonadal puberty in the setting of receiving gonadotropin-releasing hormone analog (GnRHa) and gender-affirming hormonal treatment. Additional research is needed to characterize the influence of growth and final adult height on the lived experience of TGD youth and adults and how to best assess their growth, predict their final adult height, and how medical transition can be potentially modified to help them meet their goals.
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Estatura , Disforia de Género/psicología , Personas Transgénero/psicología , Adolescente , Adulto , Imagen Corporal/psicología , Niño , Femenino , Disforia de Género/terapia , Terapia de Reemplazo de Hormonas/psicología , Humanos , Masculino , Satisfacción del Paciente , Pubertad/psicología , Procedimientos de Reasignación de Sexo/psicologíaRESUMEN
There has been little discussion of the way genomic research results should be returned and how to obtain informed consent for this. We systematically searched the empirical literature, identifying 63 articles exploring stakeholder perspectives on processes for obtaining informed consent about return of results and/or result delivery. Participants, patients and members of the public generally felt they should choose which results are returned to them and how, ranging from direct (face-to-face, telephone) to indirect (letters, emails, web-based delivery) communication. Professionals identified inadequacies in result delivery processes in the research context. Our findings have important implications for ensuring participants are supported in deciding which results they wish to receive or, if no choice is offered, preparing them for potential research outcomes.
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Comunicación , Genómica/organización & administración , Consentimiento Informado/normas , Sujetos de Investigación/psicología , Investigación/organización & administración , HumanosRESUMEN
Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders' perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.