Combating Scientific Disinformation on Gender-Affirming Care.

Scientific disinformation is false and misleading information that is used intentionally by legal and political actors to sway public opinion and oppose facts. In recent years, disinformation has become a tool for authorities to limit gender-affirming health care (GAC) for transgender and gender-expansive youth who experience gender dysphoria. Existing modes of expert intervention in health policy may not be sufficient to match the pace of these quickly unfolding health care bans.

Sporadic pituitary adenoma with somatic double-hit loss of MEN1.

Purpose: Pituitary adenomas commonly arise in patients with MEN1 syndrome, an autosomal dominant condition predisposing to neuroendocrine tumor formation, and typically diagnosed in patients with a relevant family cancer history. In these patients with existing germline loss of MEN1 on one allele, somatic loss of the second MEN1 allele leads to complete loss of the MEN1 protein, menin, and subsequent tumor formation.

Methods: Whole exome sequencing was performed on the tumor and matching blood under an institutional board approved protocol.

Primary Ovarian Insufficiency in the Prepubertal Adolescent: A Case Report.

Although there are many etiologies for delayed puberty in adolescent-aged girls, the pediatric provider should consider primary ovarian insufficiency if estradiol remains undetectable despite elevated levels of gonadotropins. Adolescent girls with this diagnosis will need holistic care from their primary care provider, focusing on both their medical and psychosocial needs. The following case study describes a 14-year-old girl who was referred to pediatric endocrinology for delayed puberty, in the setting of increased gonadotropins and undetectable estradiol.

Trends in the "Off-Label" Use of GnRH Agonists Among Pediatric Patients in the United States.

Background: Gonadotropin-releasing hormone (GnRH) agonists are FDA approved for the treatment of precocious puberty. The therapy consists of histrelin acetate (Supprelin), a surgically implanted device, or Lupron injections. In recent years, the use of these agents has been extended to include the off-label treatment of children with normally timed puberty.

Trends in the use of puberty blockers among transgender children in the United States.

Background: The objective of the study was to identify national trends in the utilization of histrelin acetate implants among transgender children in the United States.

Methods: We analyzed demographic, diagnostic and treatment data from 2004 to 2016 on the use of histrelin acetate reported to the Pediatric Health Information System (PHIS) to determine the temporal trends in its use for transgender-related billing diagnoses, e.g.

Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes.

Sequences with the capacity to adopt alternative DNA structures have been implicated in cancer etiology; however, the mechanisms are unclear. For example, H-DNA-forming sequences within oncogenes have been shown to stimulate genetic instability in mammals. Here, we report that H-DNA-forming sequences are enriched at translocation breakpoints in human cancer genomes, further implicating them in cancer etiology.

Knowledge and attitudes toward transgender health.

Background: Hormonal interventions for transgender adolescents have become increasingly common; however, there is a paucity of research on medical student knowledge of, and attitudes toward, these interventions following didactic instruction. Furthermore, no studies have examined whether students can be aware of the literature on the mental health benefits of these treatments yet continue to find them unethical.

Methods: An anonymous online survey was administered to students, from first to fourth year (n = 407), who had received one or two lectures on the treatment of youths with gender dysphoria (GD).

Development of the Yale Gender Center: An Early Progress Report.

As the need for comprehensive, affirmative health care for transgender and gender nonconforming youth has increased in recent years, clinical practice has struggled to catch up with evolving standards of care. The Yale Gender Center is an example of an interdisciplinary model of care that addresses not only clinical needs, but also ancillary needs for patients and training opportunities for students across several health disciplines. In this article, we discuss our clinical and training models, lessons learned, and our proposed directions to expand care.

Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer.

Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene, thereby inducing replication-independent, unscheduled DNA repair synthesis (UDS) preferentially in the TFO-targeted region.

Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog.

Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione.

2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog.

Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice.

2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to sulfur mustard analogues, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl sulfide.

Sulfur mustard (bis-(2-chloroethyl)sulfide) is a well-known chemical warfare agent that induces debilitating cutaneous toxicity in exposed individuals. It is also known to be carcinogenic and mutagenic because of its ability to damage DNA via electrophilic attack. We previously showed that a nucleophilic scavenger, 2,6-dithiopurine (DTP), reacts chemically with several electrophilic carcinogens, blocking DNA damage in vitro and in vivo and abolishing tumor formation in a two-stage mouse skin carcinogenesis model.

Novel benzthiodiazepinones as antiherpetic agents: SAR improvement of therapeutic index by alterations of the seven-membered ring.

A series of novel benzthiodiazepinones was studied as antiherpetic agents. Significant improvements in potency and therapeutic index in a viral replication assay were realized over the starting molecule. The role of stereospecific substitution on the diazepine ring and optimal nitrogen substitution were investigated.

Identification and characterization of a benzothiophene inhibitor of herpes simplex virus type 1 replication which acts at the immediate early stage of infection.

Analysis of a large compound library in a high throughput virus infection assay screen identified the benzothiophene PD146626 as a potent and specific inhibitor of herpes simplex virus type 1 (HSV-1) replication. PD146626 possessed an EC(50) and EC(90) against HSV-1 of 0.1 and 1 microM, respectively, and mediated no detectable cytotoxicity in cells at concentrations up to 1 microM.

Cross-reactivity of the anti-PML antibody PG-M3 with the herpes simplex virus type 1 immediate early protein ICP4.

The PML protein is one of the components of ND10, nuclear matrix-associated structures which undergo rapid disintegration at the onset of herpes simplex virus type 1 (HSV-1) infection. This disruption event has been frequently visualized in immunofluorescence assays using the anti-PML mouse monoclonal antibody PG-M3. This antibody was surprisingly found to also stain nuclear virus replication compartments when employed at higher concentrations.

Decreased insulin sensitivity and compensatory hyperinsulinemia after hormone treatment in children with short stature.

To assess the effects of GH treatment on carbohydrate and protein metabolism, we studied eight patients with short stature before and after the commencement of GH treatment. The hyperglycemic clamp procedure was employed to produce a hyperglycemic stimulus of 50 mg/dL above fasting levels for 120 min. These patients were then treated with 0.

Case report. An unusual case of precocious puberty.

An almost 3-year-old boy was evaluated for pubic hair and unilateral testicular enlargement 1 week after resection of an astrocytoma of the posterior fossa. Rather than the expected diagnosis of central precocity due to increased intracranial pressure, a diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) with testicular adrenal rest cells was made. The differential diagnosis, laboratory evaluation, and currently accepted medical management of congenital adrenal hyperplasia are described.

Resistance to neuroglycopenia: an adaptive response during intensive insulin treatment of diabetes.

Counterregulation and awareness of hypoglycemia begins at lower plasma glucose levels in insulin-dependent diabetes mellitus (IDDM) subjects given intensive insulin treatment. To determine whether these changes are associated with an alteration in the susceptibility of the brain to mild hypoglycemia, we compared central nervous system responses to hypoglycemia in 8 intensively treated (hemoglobin A1, 8.3 +/- 0.

1H NMR studies of glucose transport in the human brain.

The difference between 1H nuclear magnetic resonance (NMR) spectra obtained from the human brain during euglycemia and during hyperglycemia is depicted as well-resolved glucose peaks. The time course of these brain glucose changes during a rapid increase in plasma glucose was measured in four healthy subjects, aged 18-22 years, in five studies. Results demonstrated a significant lag in the rise of glucose with respect to plasma glucose.

Enhanced adrenomedullary response and increased susceptibility to neuroglycopenia: mechanisms underlying the adverse effects of sugar ingestion in healthy children.

Objective: Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children, but a physiologic mechanism has not been established. This study was performed to address this issue.

Design: Metabolic, hormonal, and symptomatic responses to a standard oral glucose load (1.

Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose.

Cerebral metabolism of D[1-13C]glucose was studied with localized 13C NMR spectroscopy during intravenous infusion of enriched [1-13C]glucose in four healthy subjects. The use of three-dimensional localization resulted in the complete elimination of triacylglycerol resonance that originated in scalp and subcutaneous fat. The sensitivity and resolution were sufficient to allow 4 min of time-resolved observation of label incorporation into the C3 and C4 resonances of glutamate and C4 of glutamine, as well as C3 of aspartate with lower time resolution.

Effects of puberty and diabetes on metabolism of insulin-sensitive fuels.

Insulin's ability to stimulate glucose metabolism is reduced during normal puberty; these changes are exaggerated in adolescents with insulin-dependent diabetes mellitus (IDDM). Because the effects of puberty and IDDM on the other actions of insulin have not been established, we studied leucine kinetics (using [1-13C]leucine) and fat metabolism during euglycemic hyperinsulinemia (20 mU.m2.

Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults.

The actions of recombinant human insulin-like growth factor-I (rhIGF-I) and insulin were compared in 21 healthy young (24 +/- 1 yr) and 14 healthy middle-aged (48 +/- 2 yr) subjects during 3-h paired euglycemic clamp studies using one of three doses (rhIGF-I 0.2, 0.4, and 0.