FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a disorder of brain development. Most cases lack a clear etiology or genetic basis, and the difficulty of re-enacting human brain development has precluded understanding of ASD pathophysiology. Here we use three-dimensional neural cultures (organoids) derived from induced pluripotent stem cells (iPSCs) to investigate neurodevelopmental alterations in individuals with severe idiopathic ASD. While no known underlying genomic mutation could be identified, transcriptome and gene network analyses revealed upregulation of genes involved in cell proliferation, neuronal differentiation, and synaptic assembly. ASD-derived organoids exhibit an accelerated cell cycle and overproduction of GABAergic inhibitory neurons. Using RNA interference, we show that overexpression of the transcription factor FOXG1 is responsible for the overproduction of GABAergic neurons. Altered expression of gene network modules and FOXG1 are positively correlated with symptom severity. Our data suggest that a shift toward GABAergic neuron fate caused by FOXG1 is a developmental precursor of ASD.

Segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS): Case series and review of literature.

BACKGROUND: Next-generation sequencing has greatly increased our understanding of vascular birthmarks. Many port-wine birthmarks are due to somatic mutations in GNAQ/GNA11 exon 183, but other genomic causes have been identified. Most congenital hemangiomas are due to somatic mutations in GNAQ/GNA11 at exon 209. Although genomically distinct, clinical overlap of congenital hemangiomas and port-wine birthmarks has occasionally been described. OBJECTIVE: We report a case series of a unique segmentally distributed vascular anomaly with overlapping characteristics of port-wine birthmarks and congenital hemangiomas with other distinctive features including ulceration, atrophy, and scarring. METHODS: This was a multicenter study with retrospective identification of patients via a detailed review of medical records. We also reviewed previously published cases. RESULTS: The clinical, histological, radiological, and genomic characteristics of 19 new and 13 previously reported cases characterized by segmental distribution, sharply demarcated borders, with variable thickening are presented. All cases had central atrophy with or without episodic ulceration. Those with genomic studies (13 out of 32) had somatic activating missense mutations in GNA11 or GNAQ codon 209. CONCLUSIONS: We describe the features and propose a descriptive name segmental congenital vascular anomaly with atrophy, ulceration, and scarring (SeCVAUS) for this condition.

Cutaneous body image: A window into the adolescent experience of dermatologic disease.

BACKGROUND/OBJECTIVES: Cutaneous body image (CBI) is a self-reported measure of an individual's satisfaction with their hair, skin, and nails using a psychometric survey described and validated in adult dermatology patient populations. As the CBI's clinical utility for pediatric dermatology patients has not yet been examined, we assessed the relationship between CBI scores, demographic, and clinical parameters among adolescents. METHODS: Retrospective cohort of 293 patients ages 13-18 seen at the UCSF pediatric dermatology clinic from June 2017 to February 2019. An 11-question CBI survey was administered as part of routine clinical care, querying patient satisfaction with their skin, hair, and nails on a 10-point Likert-type scale, and experience with embarrassment, bullying, and mental health care. RESULTS: Satisfaction with overall skin, skin of face, and hair significantly varied by patient age (P < .05), decreasing among subjects ages 13-16, and comparatively higher among patients ages 17-18. Mean total CBI scores did not significantly vary by sex, ethnicity, diagnosis, or new versus established patients. Mean total CBI scores were significantly higher among patients who did not report embarrassment (27.5) than among those who did (20.5) (P < .01), and among patients who had not experienced bullying (25.7) than among those who had (22.0) (P < .01). CONCLUSIONS: Objective CBI scores among adolescents correlate with reported negative experiences of skin disease (embarrassment and bullying) and with age. The CBI provides insight into the psychosocial impact of skin disease among adolescents, validates the patient's subjective perspective of their disease, and informs patient-centered discussions and management in the pediatric dermatology clinic setting.

Severe vemurafenib-induced photosensitivity in a 6-year-old boy.

Vemurafenib, a selective BRAF kinase inhibitor, has been found to induce several cutaneous adverse effects, ranging from a keratosis pilaris-like reaction to squamous cell carcinoma. While photosensitivity has been well described as one of these manifestations, we report a case of a 6-year-old boy on vemurafenib who developed a severe blistering sunburn after only two 30-minute episodes of sun exposure. A brief review of other common cutaneous adverse effects of vemurafenib is also provided.

Combination hyperbaric oxygen therapy and ustekinumab for severe hidradenitis suppurativa.

Hidradenitis suppurativa is a painful chronic inflammatory skin condition characterized by inflammatory nodules that can lead to sinus tracts and scarring. Numerous treatments have been reported, though none have reliable efficacy. Antiinflammatory agents, such as tumor necrosis factor-alpha inhibitors and interleukin inhibitors, have been used as medical therapy for refractory cases. We describe here a case of severe hidradenitis suppurativa in a pediatric patient successfully treated with a combination of high-dose ustekinumab and hyperbaric oxygen therapy.

Differences in Infant Care Practices and Smoking among Hispanic Mothers Living in the United States.

OBJECTIVE: To assess the association between maternal birth country and adherence to the American Academy of Pediatrics safe sleep recommendations in a national sample of Hispanic mothers, given that data assessing the heterogeneity of infant care practices among Hispanics are lacking. STUDY DESIGN: We used a stratified, 2-stage, clustered design to obtain a nationally representative sample of mothers from 32 US intrapartum hospitals. A total of 907 completed follow-up surveys (administered 2-6 months postpartum) were received from mothers who self-identified as Hispanic/Latina, forming our sample, which we divided into 4 subpopulations by birth country (US, Mexico, Central/South America, and Caribbean). Prevalence estimates and aORs were determined for infant sleep position, location, breastfeeding, and maternal smoking. RESULTS: When compared with US-born mothers, we found that mothers born in the Caribbean (aOR 4.56) and Central/South America (aOR 2.68) were significantly more likely to room share without bed sharing. Caribbean-born mothers were significantly less likely to place infants to sleep supine (aOR 0.41). Mothers born in Mexico (aOR 1.67) and Central/South America (aOR 2.57) were significantly more likely to exclusively breastfeed; Caribbean-born mothers (aOR 0.13) were significantly less likely to do so. Foreign-born mothers were significantly less likely to smoke before and during pregnancy. CONCLUSIONS: Among US Hispanics, adherence to American Academy of Pediatrics safe sleep recommendations varies widely by maternal birth country. These data illustrate the importance of examining behavioral heterogeneity among ethnic groups and have potential relevance for developing targeted interventions for safe infant sleep.

Childhood vitiligo impacts emotional health of parents: a prospective, cross-sectional study of quality of life for primary caregivers.

BACKGROUND/OBJECTIVES: Individuals with vitiligo have an increased risk of depression, anxiety, social isolation and detrimental effects on body image/self-esteem. However, assessments of quality of life (QoL) impact have not focused on caregivers of children with vitiligo. To address this, we determined the QoL impact in parents of children with vitiligo to assess the relationship between QoL parameters and disease duration, location, and severity. METHODS: We performed a cross-sectional study involving 123 parents of children diagnosed with vitiligo for at least 3 months, and who presented to the pediatric dermatology clinic of a major United States children's hospital. Parents completed a demographics survey, Quality of Life in a Child's Chronic Disease Questionnaire (QLCCDQ) and Family Dermatology Life Quality Index (FDLQI) to assess QoL measures. The lower the QLCCDQ score and higher the FLDQI score, the more quality of life is impaired. RESULTS: Subject age ranged from 20 to 57, and 13.9% received mental health intervention. QLCCDQ emotional domain scores were most impaired, and severity and location of disease impacted these scores. FDLQI scores decreased as children age, indicating overall parent wellbeing increased as children age. CONCLUSIONS: Childhood vitiligo has great emotional impact on the quality of life of caregivers. Recognizing this will enable dermatologist who primarily care for these patients to incorporate care giver specific interventions during clinical visits. Emotional domain scores for parents of children with vitiligo were the most impaired as much or more than of those seen in parents of children with chronic stable medical disease such as type 1 diabetes and asthma.

Facilitators and Barriers to Implementation of Safe Infant Sleep Recommendations in the Hospital Setting.

OBJECTIVE: To identify facilitators and barriers to the implementation of safe sleep recommendations from the American Academy of Pediatrics from the perspective of hospital staff as part of a needs assessment that was used to design a successful quality improvement intervention to change clinical practice. DESIGN: Qualitative design. SETTING: Multiple sites of three hospitals in the northeastern and southern United States. PARTICIPANTS: We used purposeful sampling to identify 46 participants who cared for infants on inpatient hospital units (nurses and other staff members). METHODS: A qualitative researcher used grounded theory to moderate the focus groups. We constructed the initial interview guide and then changed it as needed to capture more information about new ideas as they arose. Researchers from diverse backgrounds participated in the analysis and used the constant comparative method to select important concepts and to develop codes and subsequent themes. We continued to collect data until saturation was reached. RESULTS: We identified themes and subthemes, and the taxonomy fit into the Grol and Wensing framework for change in clinical practice. The six primary themes included The Innovation Itself, The Individual Health Care Professional, The Patient, The Social Context, The Organizational Context, and The Economic and Political Context. CONCLUSION: Participants described facilitators and barriers to the implementation of the American Academy of Pediatrics recommendations for safe infant sleep. Identification of these themes informed our quality improvement intervention to promote safe infant sleep. Findings can be used by others when faced with the need for similar change.

Variation in Safe Sleep and Breastfeeding Practices Among Non-Hispanic Black Mothers in the United States According to Birth Country.

OBJECTIVE: To examine variation in safe sleep and breastfeeding practices among US non-Hispanic black (NHB) mothers according to birth country. METHODS: We analyzed NHB mothers who were surveyed regarding safe sleep and breastfeeding practices when their infants were 2 to 6 months of age in 2011 to 2014, as part of a larger national study. We examined prevalences of safe sleep and breastfeeding practices according to birth country and examined odds of adherence to American Academy of Pediatrics recommended safe sleep and breastfeeding practices in foreign-born NHB mothers, compared with US-born NHB mothers. Our multivariate models included adjustment for maternal age, education, income, and US geographic region, and infant age at the time of the survey. RESULTS: Among 828 NHB mothers, 690 (83%) were US-born, 42 (5%) were African-born, 47 (6%) were Haitian-born, 24 (3%) were Jamaican-born, and 25 (3%) were born elsewhere. In the analysis of 803 US, African-, Haitian-, and Jamaican-born mothers, we found that Jamaican-born mothers had a lower rate of supine sleep compared with US-born mothers (40% vs 66%; adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.63). African-born mothers had lower rates of bedsharing compared with US-born mothers (11% vs 25% adjusted odds ratio, 0.22; 95% confidence interval, 0.11-0.46). Foreign-born mothers had higher rates of any and exclusive breastfeeding, compared with US-born mothers (85% and 40% vs 23% and 13%, respectively). CONCLUSIONS: Safe sleep and breastfeeding practices vary among US NHB mothers according to birth country. These data illustrate the importance of recognizing heterogeneity of safe sleep and breastfeeding practices within racial/ethnic groups.