Background: Cardiac involvement can lead to significant morbidity in children with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). However, the presentation and outcomes of cardiac involvement may differ among these 2 conditions. We aimed to compare the frequency and extent of cardiac involvement among children admitted with acute COVID-19 vs those with MIS-C. Methods: We conducted a cross sectional study of patients admitted to our hospital from March 2020 to August 2021 with symptomatic acute COVID-19 or MIS-C. Cardiac involvement was defined by presence of 1 or more of the following: elevated troponin, elevated brain natriuretic peptide, reduced left ventricular ejection fraction on echocardiogram, coronary dilation on echocardiogram, or abnormal electrocardiogram reading. Results: Among 346 acute COVID-19 patients with median age of 8.9 years and 304 MIS-C patients with median age of 9.1 years, cardiac involvement was present in 33 acute COVID-19 patients (9.5%) and 253 MIS-C patients (83.2%). The most common cardiac abnormality was abnormal electrocardiogram in acute COVID-19 patients (7.5%) and elevated troponin in MIS-C patients (67.8%). Among acute COVID-19 patients, obesity was significantly associated with cardiac involvement. Among MIS-C patients, non-Hispanic Black race/ethnicity was significantly associated with cardiac involvement. Conclusions: Cardiac involvement is much more common in children with MIS-C than in those with acute COVID-19. These results reinforce our standardized practice of performing full cardiac evaluations and follow-up in all patients with MIS-C but only in acute COVID-19 patients with signs or symptoms of cardiac involvement.

BACKGROUND: Dermatologists have the opportunity to provide medically necessary procedures, including laser hair removal, to transgender patients for gender affirmation. Further research is required to better assess the unique dermatologic needs of this population. OBJECTIVE: To examine the prevalence of dermatologic procedures among transgender people in the context of gender-affirming treatment. METHODS: This cross-sectional study examined survey responses from 696 transgender persons enrolled in the Study of Transition, Outcomes, and Gender cohort. Prevalence of self-reported dermatologic procedures was examined and compared across participant subgroups. RESULTS: Electrolysis was the most commonly reported procedure (32.9%). Transfeminine patients were more likely to use dermatologic procedures compared with transmasculine patients. Only 19 participants (2.8%) reported the use of dermal filler injections. CONCLUSION: Differences in utilization of dermatologic procedures were noted in transgender populations. Motivations, barriers, and optimal timing for gender-affirming dermatologic procedures among transgender persons should be examined in future studies.

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer cell line as a model system. More than 1700 site-specific glycoforms, represented by unique intact glycopeptides (IGPs), were identified. The treatment of 2DG had a broad effect on the N-glycoproteome, especially the high-mannose types. The glycosite occupancy of the high-mannose N-glycans decreased the most compared with the sialic acid and fucose-containing N-glycans. Many of the proteins with down-regulated high-mannose were implicated in functional networks related to response to topologically incorrect protein, integrin-mediated signaling, lysosomal transport, protein hydroxylation, vacuole, and protein N-glycosylation. The treatment of 2DG also functionally disrupted the global cellular proteome, evidenced by significant up-regulation of the proteins implicated in protein folding, endoplasmic reticulum, mitochondrial function, cellular respiration, oxidative phosphorylation, and translational termination. Taken together, these findings reveal the complex changes in protein glycosylation and expression underlying the various effects of 2DG on cancer cells, and may provide insightful clues to inform therapeutic development targeting protein glycosylation.

Moderate-to-severe acne imposes significant psychosocial and quality-of-life burdens and may be triggered by endogenous androgens or exogenous hormone therapy (HT).1–3 While moderate-to-severe acne warranting isotretinoin treatment has been observed in case series,4 the epidemiology and severity of acne in transgender populations remains to be characterized.

Introduction: Transgender and gender diverse people often face discrimination and may experience disproportionate emotional distress that leads to suicide attempts. Therefore, it is essential to estimate the frequency and potential determinants of suicide attempts among transgender and gender diverse individuals. Methods: Longitudinal data on 6,327 transgender and gender diverse individuals enrolled in 3 integrated healthcare systems were analyzed to assess suicide attempt rates. Incidence was compared between transmasculine and transfeminine people by age and race/ethnicity and according to mental health status at baseline. Cox proportional hazards models examined rates and predictors of suicide attempts during follow-up. Data were collected in 2016, and analyses were conducted in 2019. Results: During follow-up, 4.8% of transmasculine and 3.0% of transfeminine patients had at least 1 suicide attempt. Suicide attempt rates were more than 7 times higher among patients aged <18 years than among those aged >45 years, more than 3 times higher among patients with previous history of suicide ideation or suicide attempts than among those with no such history, and 2–5 times higher among those with 1–2 mental health diagnoses and more than 2 mental health diagnoses at baseline than among those with none. Conclusions: Among transgender and gender diverse individuals, younger people, people with previous suicidal ideation or attempts, and people with multiple mental health diagnoses are at a higher risk for suicide attempts. Future research should examine the impact of gender-affirming healthcare use on the risk of suicide attempts and identify targets for suicide prevention interventions among transgender and gender diverse people in clinical settings.

Background: Visual conformity with affirmed gender (VCAG) or “passing” is thought to be an important, but poorly understood, determinant of well-being in transgender people. VCAG is a subjective measure that is different from having an inner sense of being congruent with one's gender identity. Aim: We examined the frequency and determinants of VCAG and explored its association with mental health outcomes in a cohort of transgender adults. Methods: The “Study of Transition, Outcomes & Gender (STRONG)” is a cohort of transgender individuals recruited from 3 Kaiser Permanente health plans located in Georgia, Northern California and Southern California. A subset of cohort members completed a survey between 2015 and 2017. VCAG was assessed as the difference between 2 scales: scale 1 reflecting the person's sense of how they are perceived by others, and scale 2 reflecting the person's desire to be perceived. Participants were considered to have achieved VCAG when their scale 1 scores were equal to or exceeded their scale 2 scores. The frequency of VCAG and their independent associations with anxiety and depression symptoms were explored using data from 620 survey respondents including 309 transwomen and 311 transmen. Based on self-described gender identity, none of the participants identified as nonbinary or gender fluid. Outcomes: VCAG, depression, and anxiety. Results: VCAG was achieved in 28% of transwomen and 62% of transmen and was more common in persons who reported greater sense of acceptance and pride in their gender identity as measured on the Transgender Congruence Scale. Another factor associated with greater likelihood of VCAG was receipt of gender-affirming surgery, but the association was only evident among transmen. Participants who achieved VCAG had a lower likelihood of depression and anxiety with prevalence ratios (95% confidence intervals) of 0.79 (0.65, 0.96) and 0.67 (0.46, 0.98), respectively. Clinical Implications: VCAG may serve as an important outcome measure after gender-affirming therapy. Strengths and Limitations: Strengths of this study include a well-defined sampling frame and use of a novel patient-centered outcome of interest. Cross-sectional design and uncertain generalizability of results are the limitations. Conclusion: These results, once confirmed by prospective studies, may help better characterize the determinants of well-being in the transgender community, facilitating the design of interventions to improve the well-being and quality of life of this vulnerable population. To M, Zhang Q, Bradlyn A, et al. Visual Conformity With Affirmed Gender or “Passing”: Its Distribution and Association With Depression and Anxiety in a Cohort of Transgender People. J Sex Med 2020;17:2084–2092.

Protein N-glycosylation plays a vital role in diverse cellular processes, and dysregulated N-glycosylation is implicated in a variety of human diseases including neurodegenerative disorders and cancer. With recent advances in high-resolution mass spectrometry-based glycoproteomics technologies enabling large-scale N-glycoproteome profiling of disease and control samples, analysis of the large datasets has become a challenge. Here, we provide a protocol for the systems-level analysis of in vivo N-glycosylation sites on N-glycosylated proteins and their changes in human disease, such as Alzheimer's disease. The protocol includes quantitation and differential analysis of N-glycopeptide abundance, in addition to integrative N-glycoproteome and proteome data analyses, to determine disease-associated changes in N-glycosylation site occupancy and identify differentially N-glycosylated proteins in human disease versus control samples. This protocol can be modified and applied to study proteome-wide N-glycosylation alterations in response to different cellular stresses or pathophysiological states in other organisms or model systems.

Purpose: To assess the prevalence and motivations for obtaining tattoos among transgender persons. Methods: A survey of 696 transgender persons recruited from the Study of Transition, Outcomes, and Gender (STRONG) cohort evaluated the prevalence of tattoos and motivations for acquiring tattoos. Results: Transmasculine persons were more likely than transfeminine persons to have tattoos (66.5% versus 24.0%, P<0.05). Most commonly reported motivators were personal preference, aesthetics, and/or symbolism (61.8%). Scar coverage and replacement of anatomic features accounted for 10.2% of responses. Conclusion: Future studies should look into the relationship between tattoos and health status in the transgender population.

Protein N-glycosylation plays critical roles in controlling brain function, but little is known about human brain N-glycoproteome and its alterations in Alzheimer's disease (AD). Here, we report the first, large-scale, site-specific N-glycoproteome profiling study of human AD and control brains using mass spectrometry-based quantitative N-glycoproteomics. The study provided a system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites and identified disease signatures of altered N-glycopeptides, N-glycoproteins, and N-glycosylation site occupancy in AD. Glycoproteomics-driven network analysis showed 13 modules of co-regulated N-glycopeptides/ glycoproteins, 6 of which are associated with AD phenotypes. Our analyses revealed multiple dysregulated N-glycosylation-affected processes and pathways in AD brain, including extracellular matrix dysfunction, neuroinflammation, synaptic dysfunction, cell adhesion alteration, lysosomal dysfunction, endocytic trafficking dysregulation, endoplasmic reticulum dysfunction, and cell signaling dysregulation. Our findings highlight the involvement of N-glycosylation aberrations in AD pathogenesis and provide new molecular and system-level insights for understanding and treating AD.

BACKGROUND: Inadequate access to safe drinking water remains a global health problem, particularly in rural areas. Boiling is the most commonly used form of point-of-use household water treatment (HWT) globally, although the use of bottled water in low-and middle-income countries (LMICs) is increasing rapidly. OBJECTIVES: We assessed the regional and seasonal prevalence of HWT practices (including bottled water use) in low-income rural areas in two Chinese provinces, evaluated the microbiological safety of drinking water and associated health outcomes, and estimated the air pollution burden associated with the use of solid fuels for boiling. METHODS: We conducted cross-sectional surveys and collected drinking water samples from 1,033 rural households in Guangxi and Henan provinces. Temperature sensors affixed to pots and electric kettles were used to corroborate self-reported boiling frequencies and durations, which were used to model household air pollution (HAP) in terms of estimated particulate matter ≤2:5 lm in aerodynamic diameter (PM2:5) concentrations. RESULTS: Based on summer data collection in both provinces, after controlling for covariates, boiling with electric kettles was associated with the largest log reduction in thermotolerant coliforms (TTCs) (−0:66 log10 TTC most probable number/100 mL), followed by boiling with pots (−0:58), and bottled water use (−0:39); all were statistically significant (p <0:001). Boiling with electric kettles was associated with a reduced risk of TTC contamination [risk ratio ðRRÞ =0:25, p <0:001] and reported diarrhea (RR = 0:80, p =0:672). TTCs were detected in 51% (n = 136) of bottled water samples. For households boiling with biomass, modeled PM2:5 concentrations averaged 79 lg/m3 (standard deviation = 21). DISCUSSION: Our findings suggest that where boiling is already common and electricity access is widespread, the promotion of electricity-based boiling may represent a pragmatic stop-gap means of expanding safe water access until centralized, or decentralized, treated drinking water is available; displacing biomass use for water boiling could also reduce HAP concentrations and exposures. Our results also highlight the risks of increasing bottled water use in rural areas, and its potential to displace other sources of safe drinking water, which could in turn hamper efforts in China and other LMICs toward universal and affordable safe water access. https://doi.org/10.1289/EHP7124.