Longitudinal impact of gender-affirming endocrine intervention on the mental health and well-being of transgender youths: preliminary results.

BACKGROUND/AIMS: Transgender youths experience high rates of depression and suicidal ideation compared to cisgender peers. Previous studies indicate that endocrine and/or surgical interventions are associated with improvements to mental health in adult transgender individuals. We examined the associations of endocrine intervention (puberty suppression and/or cross sex hormone therapy) with depression and quality of life scores over time in transgender youths. METHODS: At approximately 6-month intervals, participants completed depression and quality of life questionnaires while participating in endocrine intervention. Multiple linear regression and residualized change scores were used to compare outcomes. RESULTS: Between 2013 and 2018, 50 participants (mean age 16.2 + 2.2 yr) who were naïve to endocrine intervention completed 3 waves of questionnaires. Mean depression scores and suicidal ideation decreased over time while mean quality of life scores improved over time. When controlling for psychiatric medications and engagement in counseling, regression analysis suggested improvement with endocrine intervention. This reached significance in male-to-female participants. CONCLUSION: Endocrine intervention may improve mental health in transgender youths in the US. This effect was observed in both male-to-female and female-to-male youths, but appears stronger in the former.

Selective integrin endocytosis is driven by interactions between the integrin α-chain and AP2.

Integrins are heterodimeric cell-surface adhesion molecules comprising one of 18 possible α-chains and one of eight possible ß-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalized by clathrin-mediated endocytosis (CME) through ß subunit-based motifs found in all integrin heterodimers. However, whether specific integrin heterodimers can be selectively endocytosed was unknown. Here, we found that a subset of α subunits contain an evolutionarily conserved and functional YxxΦ motif directing integrins to selective internalization by the most abundant endocytic clathrin adaptor, AP2. We determined the structure of the human integrin α4-tail motif in complex with the AP2 C-µ2 subunit and confirmed the interaction by isothermal titration calorimetry. Mutagenesis of the motif impaired selective heterodimer endocytosis and attenuated integrin-mediated cell migration. We propose that integrins evolved to enable selective integrin-receptor turnover in response to changing matrix conditions.

Crude Garlic Extract Inhibits Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis of Cancer Cells In Vitro.

Garlic and its lipid-based extracts have played an important medicinal role in humans for centuries that includes antimicrobial, hypoglycemic, and lipid-lowering properties. The present study was to investigate the effects of crude garlic extract (CGE) on the proliferation of human breast, prostate, hepatic, and colon cancer cell lines and mouse macrophageal cells, not previously studied. The human cancer cell lines, such as hepatic (Hep-G2), colon (Caco-2), prostate (PC-3), and breast (MCF-7), were propagated at 37°C; air/CO2 (95:5 v/v) using the ATCC-formulated RPMI-1640 Medium and 10% fetal bovine serum (FBS), while the mouse macrophage cell line (TIB-71) was propagated at 37°C; air/CO2 (95:5 v/v) using the ATCC-formulated DMEM and 10% FBS. All cells were plated at a density of ∼5000 cells/well. After overnight incubation, the cells were treated with 0.125, 0.25, 0.5, or 1 µg/mL of CGE an additional 72 h. Inhibition of cell proliferation of 80-90% was observed for Hep-G2, MCF-7, TIB-71, and PC-3 cells, but only 40-55% for the Caco-2 cells when treated with 0.25, 0.5, or 1 µg/mL. In a coculture study of Caco-2 and TIB-71 cells, inhibition of cell proliferation of 90% was observed for Caco-2 cells compared to the 40-55% when cultured separately. CGE also induced cell cycle arrest and had a fourfold increase in caspase activity (apoptosis) in PC-3 cells when treated at a dose of 0.5 or 1 µg/mL. This investigation of CGE clearly highlights the fact that the lipid bioactive compounds in CGE have the potential as promising anticancer agents.

Prospective memory and glycemic control in children with type 1 diabetes mellitus: a cross-sectional study.

BACKGROUND: Prospective memory is that memory which is required to carry out intended actions and is therefore essential in carrying out the daily activities required in the self-management of type 1 diabetes mellitus (T1DM). This study aimed to identify the relationships between prospective memory and diabetic control in children with T1DM. METHOD: 94 children aged 6-18 years with T1DM completed an innovative prospective memory screen, PROMS, and a series of cognitive tests. Parents answered questionnaires about their children's diabetic histories and cognitive skills. RESULTS: No association between total PROMS score and glycemic control was found. Lower HbA1C was associated with higher (better) scores on the 20 minute event-based task on the PROMS. Parental concerns about working memory and metacognition in their children were mirrored by higher HbA1C. CONCLUSIONS: This study suggests that there may be an association between glycemic control and prospective memory for event based tasks. Additional studies need to be done to determine reproducibility, causality, and if prospective memory based interventions can improve diabetic control.

Growth hormone deficiency and diabetes insipidus as a complication of endoscopic third ventriculostomy.

Endoscopic third ventriculostomy (ETV) has become the procedure of choice for the treatment of obstructive hydrocephalus in children and adults. Endocrinological complications of ETV in children are rare. Diabetes insipidus (DI) is the most common and accounts for only 0.5% of complications from ETV. The majority of documented cases are transient. To date, there are no documented cases of multiple pituitary hormone deficiencies. We present here a 6-year-old girl with growth hormone deficiency and permanent DI which developed as a complication of ETV. This patient is unique in both demonstrating multiple pituitary hormone deficiencies and the classical triphasic response of DI after ETV. We postulate that these complications were caused by compression of the pituitary stalk and hypothalamic injury during the procedure. We compare our case presentation to experimental studies conducted in rats.

Long-term efficacy of insulin pump therapy in children with type 1 diabetes mellitus.

OBJECTIVE: Insulin pumps have been well established for insulin delivery. However, questions about long-term efficacy of insulin pump therapy still remain. We evaluated the long-term efficacy of continuous insulin infusion pump therapy (CSII) in pediatric patients with type 1 diabetes mellitus (T1DM). METHODS: This was a retrospective observational study which included 131 patients with T1DM who transitioned to an insulin pump from multiple daily insulin (MDI) injections between 1999 and 2009 and were followed by one endocrinologist. Data were collected from 6 months prior to switching to CSII to 30 months after initiation of CSII and included glycated hemoglobin (HbA1c) and insulin requirement. Of the 131 patients, 45 had complete data consisting of a visit and HbA1c every 6 months for 30 months after transition to CSII and were included for analysis. RESULTS: Mean HbA1c prior to starting the CSII was 8.0 +0.9 %, 7.7 +1.0 % at 6 months and 7.8+1.2 % at 1 yr post initiation of CSII. However, at 30 months, HbA1c increased to 8.0+1.3%. A trend in transient improvement in HbA1c was limited only to those patients >11 yr of age and those requiring >0.75 u/kg/day of insulin at transition and was not seen in those <11 yr of age or those requiring <0.75 u/kg/day and did not persist beyond 1 year. CONCLUSIONS: There was no long-term significant difference in glycemic control in patients with CSII as compared to MDI.

Consultation with the specialist: thyroid nodules.

Based on strong research evidence, thyroid nodules in children and teenagers are more likely to be malignant than in adults. Based on strong research evidence, a history of ionizing radiation to the head or neck is an independent risk factor for the development of thyroid malignancies. There is strong research evidence, including a recent meta-analysis, supporting the use of fine-needle aspiration biopsy in the evaluation of all pediatric and adolescent patients presenting with a thyroid nodule. The surgical management and postoperative care of pediatric and adolescent patients who have well-differentiated thyroid carcinomas remains controversial, because the rarity of the disease limits the ability to conduct randomized, prospective research studies. Numerous studies have demonstrated that, despite presenting with more advanced disease, pediatric and adolescent patients with thyroid carcinoma have a higher survival rate than adults. The American Thyroid Association has issued strong evidence-based recommendations for the management of medullary thyroid carcinoma, including RET mutation testing and early prophylactic total thyroidectomy in children with high-risk mutations.

A nanoemulsion formulation of dacarbazine reduces tumor size in a xenograft mouse epidermoid carcinoma model compared to dacarbazine suspension.

Dacarbazine (DAC) is an anticancer drug that has been used to treat various types of cancers. The aim of the current study was to test whether there is an increased efficacy of DAC as a nanoemulsion on reducing tumor size in an epidermoid carcinoma xenograft mouse model. Tumors were induced in 5-week-old nude mice by subcutaneous injection. The mice were untreated or treated with a suspension of DAC (0.1 mg/kg), a nanoemulsion of DAC (0.1 mg/kg), or Nano-Control (same composition as the suspension and nanoemulsion but no DAC), every 2 days by either intramuscular injection (IM) or topical application. After 40 days, the final tumor size of mice receiving the nanoemulsion of DAC IM (0.83 ± 0.55 mm(3)) was significantly reduced compared to the suspension of DAC IM (4.75 ± 0.49 mm(3)), Nano-Control IM (7.63 ± 0.91 mm(3)), and untreated (10.46 ± 0.06 mm(3)). The final tumor size of mice receiving the nanoemulsion of DAC topically (3.33 ± 0.63 mm3) was also significantly reduced compared to the suspension of DAC topically (7.64 ± 0.68 mm(3)). This increased efficacy maybe partially attributed to: 1) the reduced particle size of the nanoemulsion in comparison with suspension (111 versus > 6000 nm), 2) reduction in zeta potential of the nanoemulsion compared to suspension (-3.2 versus -89.1 mV), 3) production of a stable water dispersion relative to unstable suspension, 4) decreased polydispersity index of the nanoemulsion compared to suspension, and 5) greater stability of drug with the nanoemulsion in comparison with the suspension. FROM THE CLINICAL EDITOR: In this clinically relevant study, the anti-tumor efficacy of dacarbazine was found to be significantly increased as a nanoemulsion in epidermoid carcinoma xenograft mice, both with IM and topical administration.

Encapsulation of cadmium selenide quantum dots using a self-assembling nanoemulsion (SANE) reduces their in vitro toxicity.

Although, nanometer-scale semi-conductor quantum dots (QDs) have attracted widespread interest in medical diagnosis and treatment, many can have intrinsic toxicities, especially those composed of CdSe, associated with their elemental composition. Using our self-assembling nanoemulsion (SANE) formulations which we have previously reported to be composed of non-toxic components, i.e., such as vegetable oil, surfactant and water, we hypothesized that their appropriate utilization would reduce the toxicity of QDs by encapsulating the CdSe QDs in our (SANE) system using a modified phase-inversion temperature (PIT) method. SANE encapsulation of the QDs did not alter their emission wavelength of 600nm which remained unchanged during the encapsulation process. In contrast, zeta potential of encapsulated QDs was reduced from -30 to -6.59 mV, which we have previously reported to be associated with beneficial properties (increased bioavailability and efficacy) for SANE-encapsulated bioactives such as pharmaceuticals. Relative to the untreated controls, the viability of HeLa cells exposed for 48 h to un-encapsulated CdSe QDs at a concentration of 115 µg/mL was 22.7±1.7% (p<0.05). In contrast, the percentage of viable HeLa cells following exposure to SANE-encapsulated CdSe QDs at the same concentration was 91.6±3.5% (p<0.05) or a 307% increase in the number of viable cells (p<0.05). When the dose of CdSe QDs was increased to 230 µg/mL, the percentage of viable HeLa cells after exposure to the un-encapsulated CdSe QDs was 16.1±1.3% compared to controls (p<0.05). In contrast, at the same increased concentration (230 µg/mL) of un-encapsulated CdSe QDs, the percentage of viable HeLa cells following exposure to SANE-encapsulated CdSe QDs was 87.9±3.3% relative to controls (p<0.05) or a 448% increase in the number of viable cells (p<0.05). Exposure of HeLa cells to a nanoblank, (nanoemulsion without QDs), showed no significant effect on cell viability (97.2±2.5%) compared to control cell culture. In conclusion, application of our SANE technology for encapsulating QDs increased cell viability of cells exposed to CdSe QDs while maintaining the original emission wavelength and therefore may be applied to reduce QD toxicity.

Increased consumption of dietary cholesterol, lutein, and zeaxanthin as egg yolks does not decrease serum concentrations and lipoprotein distribution of other carotenoids, retinol, and tocopherols.

We have previously reported that consumption of lutein and zeaxanthin as 2 and 4 egg yolks per day for 5 weeks significantly increased serum lutein and zeaxanthin concentrations in older adults taking cholesterol-lowering statins. We hypothesized that increased consumption of eggs, lutein, and zeaxanthin may correlate with decreased absorption of other carotenoids and increased absorption of vitamins A and E, thus affecting their serum concentrations and lipoprotein distribution. Fifty-two subjects aged at least 60 years consumed 2 egg yolks per day followed by 4 egg yolks per day for 5 weeks each with a 4-week egg-free period at baseline and between the 2 interventions. Mean serum ß-cryptoxanthin, lycopene, α-carotene, ß-carotene, α-tocopherol, and retinol concentrations did not change during the 2 and 4 egg yolk phases. Mean serum α-cryptoxanthin and γ-tocopherol concentrations did not change after the 2 egg yolk phase, but increased by 47% (P < .001) and 19% (P < .05), respectively, after the 4 egg yolk phase. The percentage distribution of carotenoids and tocopherols between the high-density lipoprotein (HDL) and non-HDL fractions was not significantly different during the egg yolk phases compared with baseline despite the significant increases in lutein and zeaxanthin carried on HDL and non-HDL fractions. In conclusion, increased dietary cholesterol, lutein, and zeaxanthin consumed as egg yolks did not decrease the absorption of other carotenoids, and increased γ-tocopherol but not retinol as evidenced by their serum and lipoprotein concentrations. Two and 4 egg yolk consumption increases serum and retinal lutein and zeaxanthin without altering the serum status of the other carotenoids, tocopherol, and retinol.

Reversible pituitary hyperplasia at birth in a macrosomic full-term baby boy.

Pituitary hyperplasia is generally associated with end-organ failure such as primary hypothyroidism, physiological changes such as puberty and pregnancy, or neoplasms secreting releasing factors. We present a full-term infant with an enlarged pituitary height of 8 mm at age 3 days despite a normal endocrinological evaluation. Repeat imaging at 5 months of age revealed a normal-size pituitary gland. To our knowledge, pituitary hyperplasia has not been described in a neonate with normal pituitary function.

Prime-time hypoglycemia: factitious hypoglycemia during insulin-pump therapy.

Unexplained hypoglycemia in a pediatric diabetic patient can perplex even the savviest health care providers and lead to an extensive medical workup. We present here the cases of 2 children with type 1 diabetes mellitus treated with insulin pumps who were hospitalized for episodes of hypoglycemia. Review of their insulin pumps revealed normal basal and bolus insulin delivery. However, subsequent review of the priming history in the pump revealed that both children were receiving additional insulin under the manual-prime function, which is not included in the daily totals and, therefore, was initially unnoticed. Ultimately, both children confessed to surreptitiously using this priming function to self-administer extra insulin. It is important that health care professionals who are caring for diabetic patients be aware of this possibility.

The effect of oral leucine on protein metabolism in adolescents with type 1 diabetes mellitus.

Lack of insulin results in a catabolic state in subjects with insulin-dependent diabetes mellitus which is reversed by insulin treatment. Amino acid supply, especially branched chain amino acids such as leucine, enhances protein synthesis in both animal and human studies. This small study was undertaken to assess the acute effect of supplemental leucine on protein metabolism in adolescents with type 1 diabetes. L-[1-(13)C] Leucine was used to assess whole-body protein metabolism in six adolescent females (16-18 yrs) with type 1 diabetes during consumption of a basal diet (containing 58 µmoles leucine/kg/h) and the basal diet with supplemental leucine (232 µmoles leucine/kg/h). Net leucine balance was significantly higher with supplemental leucine (56.33 ± 12.13 µmoles leucine/kg body weight/hr) than with the basal diet (-11.7 ± -5.91, P < .001) due to reduced protein degradation (49.54 ± 18.80 µmoles leucine/kg body weight/hr) compared to the basal diet (109 ± 13.05, P < .001).

Does pituitary stalk function improve with age?

Ectopic posterior pituitary hyperintensity on MRI is a common feature associated with growth hormone deficiency. The presence of at least some residual components of the pituitary stalk is necessary for adequate anterior pituitary function. Little is known about long-term change in pituitary function or MRI findings in patients with ectopic posterior pituitary and interrupted pituitary stalk. We describe a case of childhood growth hormone deficiency and hyperprolactinemia associated with absent pituitary stalk. As an adult, prolactin levels normalized and GH secretion improved associated with changes in MRI findings.

Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment concentrations in older adults with low macular pigment taking cholesterol-lowering statins.

BACKGROUND: Lutein and zeaxanthin may reduce the risk of dry, age-related macular degeneration because of their photo-oxidative role as macular pigment. OBJECTIVE: The present study evaluated serum lutein, zeaxanthin, and macular pigment optical density (MPOD) responses at 0.25 degrees , 0.5 degrees , and 1 degree retinal eccentricities to the consumption of 2 and 4 egg yolks/d by older adults taking cholesterol-lowering medications. DESIGN: Subjects consumed foods containing 2 followed by 4 egg yolks/d for 5 wk each with a 4-wk egg-free period at baseline and between the 2 interventions. RESULTS: Changes in MPOD (n = 37) with egg yolk consumption were inversely associated (P < 0.05) with baseline MPOD. Subjects with low-baseline MPOD (defined as MPOD < or =0.5 at 0.25 degrees , < or =0.4 at 0.5 degrees , and < or =0.35 at 1 degrees ) showed increases of < or =50% (P < 0.05) with 4 egg yolks at the 3 retinal eccentricities. MPOD increased by 31% (P = 0.059) at 0.5 degrees with 2 egg yolks. Serum lutein increased by only 16% and 24% (P < 0.05) compared with increases of 36% and 82% (P < 0.001) in serum zeaxanthin (n = 52) after consumption of 2 and 4 egg yolks, respectively. Serum HDL cholesterol increased by 5% (P < 0.05) after consumption of 2 and 4 egg yolks. Serum LDL cholesterol did not change with either egg yolk treatment. CONCLUSIONS: Consumption of 4 egg yolks/d, and possibly of 2 egg yolks/d, for 5 wk benefited macular health in older adults with low MPOD. Serum HDL cholesterol increased without an increase in LDL cholesterol in this study population, most of whom were taking cholesterol-lowering statins.

Cytology and flow cytometry to identify ectopic thymic tissue masquerading as a thyroid nodule in two children.

BACKGROUND: Clinically unapparent thyroid nodules in children pose a significant problem in differential diagnosis and management. Ectopic thymic tissue in the thyroid gland is rare, but may masquerade as a thyroid nodule. This paper demonstrates the utility of flow cytometry as an adjunct to cytology by fine needle aspiration in diagnosing ectopic thymic tissue in the thyroid gland. SUMMARY: By demonstration of T lymphocytes maturing along two cell lineages and the absence of markers for malignant lesions, fine-needle aspiration, cytology, and flow cytometry were used to identify ectopic thymic tissue masquerading as a thyroid nodule in two children. CONCLUSION: Use of this technique prevented surgical intervention that otherwise would have been necessary to obtain an accurate diagnosis of these thyroid nodules.

Effect of insulin with oral nutrients on whole-body protein metabolism in growing pubertal children with type 1 diabetes.

Insulin treatment of children with insulin-dependent diabetes mellitus improves whole body protein balance. Our recent study, conducted in pubertal children with type 1 diabetes with provision of both insulin and amino acids, indicated a positive effect of insulin on protein balance, primarily through decreased protein degradation. The current study was undertaken to assess the effect of insulin on protein metabolism in adolescents with type 1 diabetes during oral provision of a complete diet. Whole-body protein metabolism in six pubertal children (13-17 y) with type 1 diabetes mellitus was assessed with L-[1-13C]leucine during a basal (insulin-withdrawn) period and during infusion of 0.15 U/kg/h regular insulin with hourly meals to meet protein and energy requirements. Net leucine balance was significantly higher with insulin and nutrients (13.1 +/- 6.3 micromol leucine/kg/h) than in the basal state (-21.4 +/- 2.8, p < 0.01) with protein degradation decreased from 138 +/- 5.6 mumol leucine/kg/h to 108 +/- 5.9 (p < 0.01) and no significant change in protein synthesis. Even with an ample supply of nutrients, insulin does not increase whole-body protein synthesis in pubertal children with type 1 diabetes mellitus and positive protein balance is solely due to a substantial reduction in the rate at which protein is degraded.

Effect of inspiration/expiration on height measurement.

BACKGROUND: Growth parameters are a powerful screening tool in pediatric care. Accuracy assumes differing importance in different clinical settings. A small error is not clinically significant when height is obtained as a screening tool during annual well child visits. However, when assessing annual growth velocity using shorter interval visits, an error of equal magnitude might influence further management decisions. AIM AND HYPOTHESIS: To explore the effect of inspiration or expiration on height measurement. Our hypothesis was that height measurements obtained in inspiration would be greater than those obtained in expiration or without specific instructions as to status of respiration (unspecified). METHODS: Heights of 99 individuals 8 years and older were measured in inspiration, expiration and unspecified respiratory status by two pediatric endocrinologists. Patients were measured three times in each mode. The p values were adjusted by Tukey procedure for multiple comparisons among three modes. RESULTS: Height measurement performed in inspiration, expiration or without specific instruction as to breathing (unspecified) did affect height measurement. Mean difference +/- SEM (95% CI) between height obtained in inspiration and expiration was 0.22 +/- 0.03 cm (95% CI: 0.15, 0.29); between inspiration and unspecified 0.31 +/- 0.04 cm (95% CI: 0.22, 0.40); and between expiration and unspecified 0.092 +/- 0.03 cm (95% CI: 0.03, 0.16). CONCLUSIONS: Based on these results, we recommend multiple height measurements using uniform technique including inspiratory/expiratory status, especially when calculating 'annualized' height velocity over short intervals.

Congenital nephrotic syndrome and persistent hypothyroidism after bilateral nephrectomy.

Congenital nephrotic syndrome is commonly associated with hypothyroidism. Thyroid hormone supplementation is recommended as standard of care. The hypothyroidism is postulated to occur secondary to chronic massive proteinuria with loss of thyroid binding globulin, thyroid hormone and iodine. Previous reports have indicated that thyroxin may be discontinued following bilateral nephrectomy. We report our experience with one child with congenital nephrotic syndrome, Finnish type, and hypothyroidism who had a high requirement for thyroxin (100-150 microg/d) from infancy to 4 years of age. Hypothyroidism persisted despite bilateral nephrectomy and later following renal transplantation. However, his thyroxin requirement is now substantially lower (62.5 microg/d) at age 14 years. No goiter was detected clinically and antithyroid antibodies were negative. Thyroid ultrasound and 123I scan revealed a thyroid gland in the anatomically normal location. 123I uptake was elevated, 18% at 6 hours and 51% at 24 hours (normal values: 3-16% at 6 hours and 8-25% at 24 hours). Perchlorate was unavailable for a perchlorate washout study. We speculate that this patient may have an intrinsic problem with thyroid hormone synthesis. It is unclear whether this is related or coincidental to the Finnish nephrotic syndrome. We recommend following thyroid functions closely if thyroxin is discontinued following bilateral nephrectomies in Finnish type congenital nephrotic syndrome.