Electrical Synapses Mediate Embryonic Hyperactivity in a Zebrafish Model of Fragile X Syndrome.

Although hyperactivity is associated with a wide variety of neurodevelopmental disorders, the early embryonic origins of locomotion have hindered investigation of pathogenesis of these debilitating behaviors. The earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons (MNs) that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Gap junction electrical synapses drive early spontaneous behavior in zebrafish, prior to the emergence of chemical neurotransmitter networks. We use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show altered sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 34/35. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. We also use functional imaging to examine MN and interneuron (IN) activity in early embryogenesis, finding genetic disruption of electrical gap junctions uncouples activity between mnx1 + MNs and INs. Taken together, our work highlights the importance of electrical synapses in motor development and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initial formation of locomotive circuits.

Differences in Patient and Parent Informant Reports of Depression and Anxiety Symptoms in a Clinical Sample of Transgender and Gender Diverse Youth.

Purpose: We assessed characteristics of patients at a pediatric gender clinic and investigated if reports of mental health concerns provided by transgender and gender diverse (TGD) youth patients differed from reports provided by a parent informant on their behalf. Methods: This cross-sectional study included 259 TGD patients 8 to 22 years of age attending a pediatric gender clinic in the southeast United States from 2015 to 2020. Pearson correlations and paired sample t-tests compared patient-reported mental health concerns at patient intake with those provided by a parent informant. Clinical symptom severity was assessed with standardized T-scores. Level 2 Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Depression Scale and Level 2 PROMIS Emotional Distress-Anxiety Scale assessed depression and anxiety symptoms of patients. Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Parent/Guardian-Rated Level 1 Cross-Cutting Symptom Measure was used with parents. Results: Patients had a mean age of 14.9 at first visit, with most identifying as White (85.5%), non-Hispanic (91.1%), and as a boy or man (63.6%). Half had moderate-to-severe depression (51.2%) or anxiety (47.9%) symptoms. There was a moderate, positive correlation between patient-reported and parent-reported depression symptoms, with no correlation for anxiety symptoms. Informant type differences were statistically significant (patients reporting greater depression and anxiety symptoms). Conclusions: TGD youth patients reported more severe depression and anxiety symptoms compared with parent informants. Despite moderate agreement on depression symptoms, parents did not accurately detect their child's anxiety symptoms. These discrepancies highlight a need for interventions which increase parental recognition of child mental health status.

Care and Cancer Screening of the Transgender Population.

As sex and gender are assigned at birth before gender identity development, many individuals experience feelings of discordance between their gender identity and their sex and gender assigned at birth. The transgender community has not been well understood by medical and mental health fields. As such, this marginalized and vulnerable community faces multiple barriers to receiving health maintenance and specialized care, both at the community and patient-specific level. Many transgender individuals undergo some form of transition to the gender that matches their gender identity. Transition efforts look different for each patient because gender and gender identity occur along a continuum. Transition may include social, hormonal, and/or surgical components. As providers are caring for transgender patients, it is imperative to understand where a patient is in their gender transition and how hormonal and/or surgical therapies affect their cancer risk and screening. The aim of this article is to describe appropriate cancer screening practices and important care considerations for the primary care physician and generalist gynecologist taking care of transgender individuals.

Approaches to Vaginal Bleeding and Contraceptive Counseling in Transgender and Gender Nonbinary Patients.

The transgender community has faced a long-standing history of prejudice and discrimination that has negatively affected their health. A lack of health care provider education and comfort with transgender medicine further challenges the ability of this population to obtain competent, gender-affirming medical care. As with all patients, a thorough patient history with avoidance of assumptions of sexual orientation based on gender identity is integral to providing appropriate care for transgender individuals. Vaginal bleeding in transgender men should be evaluated in a similar manner to natal women, and with knowledge of the individual's present reproductive organs. The majority of transgender men receiving gender-affirming hormone therapy will have cessation of menses by 6 months of continuous use; thus, bleeding beyond this interval warrants measurement of hormone levels and further evaluation. Progesterone-only contraceptive methods including progesterone-only pills, medroxyprogesterone acetate, or a levonorgestrel intrauterine device can be used in transgender men and nonbinary patients with continued menses despite physiologic testosterone levels, or to act as a bridge method for menstrual cessation at the time of testosterone initiation. For bleeding refractory to progesterone methods, health care providers should discuss surgical options or the use of aromatase inhibitors with their patients. Counseling on fertility desires and family planning is integral to improving the reproductive care of transgender patients. Contraceptive counseling for transgender patients should include not only the efficacy and ease of use of available methods, but also discussion of advantages and disadvantages of contraceptive options with regard to the patient's gender identity.

Best Practices in Transgender Health: A Clinician's Guide.

Providing culturally competent and medically knowledgeable care to the transgender community is increasingly falling within the realms of practice for primary care providers. The purpose of this article is to provide an overview of best practices as they relate to transgender care. This article is by no means a comprehensive guide, but rather a starting point for clinicians as they provide high-quality care to their transgender patients.