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Abstract. During a 12-month period 80 children >3 months of age seen at an emergency room with acute fevers Is greater than or equal to 39.7 C (103.5 F) and no localizing signs of infection were studied using blood and buffy coat cultures to isolate bacteria and viruses. Bacteremia was identified in three children (3.8%): two with Streptococcus pneumoniae and one with Neisseria meningitidis. Two children with viremia were identified: both isolates were ECHO virus, types 11 and 21, respectively. Fifty-eight of the study children (72%) were seen again in 24 to 48 hours and 27/58 (46%) were afebrile and completely well. No differences in sex, age, or initial WBC count existed among these children who returned afebrile and well and those with either localized disease or those persistently febrile. Pediatrics 68:157-160, 1981; fever, bacteremia, viremia, outcome. [ABSTRACT FROM AUTHOR]

We have restudied a fibroblast cell line from a female with marked manifestations of X linked hypohidrotic ectodermal dysplasia (HED) and a balanced X;9 translocation. Chromosome analysis showed a karyotype of 46,X,t(X;9)(q13.1;p24) with an Xq breakpoint distal to the one previously reported. The significance of the cell line, previously unrecognised, for the mapping and eventual cloning of the HED locus is discussed. [ABSTRACT FROM PUBLISHER]

Abstract Background Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. Methods We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. Results Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. Conclusions This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.

Objective: This report explores the experiences of preclinical medical students who led group dialectical behavior therapy (DBT) for a student-run LGBTQ + mental health clinic., Methods: In the clinic, experienced clinicians trained and supervised preclinical medical students to facilitate DBT groups. The authors conducted a qualitative study to understand the impact of the DBT groups on the student facilitators via semi-structured interviews, which were evaluated using thematic analysis., Results: The clinic hosted nine iterations of group DBT facilitated by preclinical medical students, involving 18 student leaders and 30 patients. Twelve student facilitators were interviewed. Participants had a diverse array of specialty interests and were primarily motivated by the opportunity for early clinical experience. They reported improved clinical skills, increased appreciation of psychotherapy as a treatment modality, and increased interest in incorporating psychotherapy in their future practice. Furthermore, participants reported using DBT skills to cultivate wellbeing during clerkship year and in their personal lives., Conclusions: Offering preclinical medical students the opportunity to lead group DBT therapy is a novel educational model providing early training in psychotherapy techniques. This opportunity for early direct patient experience in a supervised group setting attracted medical students with a diverse range of specialty interests. This model provided medical students specific DBT skills to implement in future patient care interactions and to maintain their personal wellbeing throughout medical training. The broad appeal and lasting effects of this program may prove beneficial at other institutions., (© 2024. The Author(s), under exclusive licence to Academic Psychiatry, LLC.)

Introduction: LGBTQ+ individuals experience disproportionately high rates of mental health disorders. Subpopulations of this community experience unique risk factors and barriers to accessing care., Method: This study analyzes chart review data of patients (n=49) of an LGBTQ+-specific, student-run, free mental health clinic in NYC between March 2019 and July 2021., Result: Most common diagnoses were mood disorders (55%) and anxiety disorders (53%). 88% of patients reported experiencing lifetime traumatic events; 20% of patients met criteria for PTSD., Conclusion: Further research is needed to characterize vulnerable subpopulations to create equitable, accessible, and competent mental health care resources for the LGBTQ+ community., Competing Interests: Conflicts of Interest: The authors declare that they have no conflicts of interest and certify responsibility for the manuscript.

Objective: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals report higher rates of exposure to traumatic events and posttraumatic stress disorder (PTSD) compared with heterosexual and cisgender individuals. No treatment outcomes research has focused on PTSD in the LGBTQ population. Trauma-focused psychodynamic psychotherapy (TFPP) is a brief, manualized, attachment- and affect-focused psychotherapy for PTSD. TFPP explicitly incorporates broad identity-related and societal factors into its conceptualization of trauma and its consequences, which may be especially helpful for LGBTQ patients with minority stress who seek affirmative care., Methods: Fourteen LGBTQ patients with PTSD, assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), received 24 sessions of twice-weekly (12 weeks) TFPP via teletherapy provided by supervised early-career therapists inexperienced in the modality. Sessions were videotaped to monitor therapists' treatment adherence. Patients were assessed at baseline, week 5, termination (week 12), and 3 months posttreatment for PTSD symptoms (assessed with the CAPS-5) and secondary outcomes., Results: TFPP was well tolerated by patients, with 12 (86%) completing the intervention. CAPS-5-measured PTSD symptoms, including dissociation, significantly improved during treatment (mean decrease=-21.8, d=-1.98), and treatment gains were maintained at follow-up. Most patients experienced PTSD clinical response (N=10, 71%) or diagnostic remission (N=7, 50%). Patients generally experienced significant, concomitant improvements in complex PTSD symptoms, general anxiety, depression, and psychosocial functioning. Adherence to the intervention among therapists was high, with 93% of rated sessions meeting adherence standards., Conclusions: TFPP shows promise in the treatment of PTSD among sexual and gender minority patients seeking LGBTQ-affirmative PTSD care., Competing Interests: Dr. Milrod is a coauthor of Trauma-Focused Psychodynamic Psychotherapy: A Step-by-Step Treatment Manual and receives royalties from Oxford University Press. The other authors report no financial relationships with commercial interests.

The Weill Cornell Medicine Wellness Qlinic (Wellness Qlinic) is a student-run mental health clinic serving the lesbian, gay, bisexual, transgender, and queer (LGBTQ +) community in New York City. Student-run clinics have successfully provided primary care to underserved communities experiencing barriers to accessing health care. Psychiatric evaluation and medication management have also been implemented in several student-run clinics, but providing sustainable psychotherapy services has been a challenge. In this paper, we present a student-run mental health program incorporating interdisciplinary trainees to provide robust short-term psychiatric treatment, including individual psychotherapy, medication management, and group therapy. Results of a chart-review study to evaluate patient engagement and treatment outcomes are presented. The Wellness Qlinic's treatment model resulted in 90% patient retention and positive clinical outcomes for patients while addressing an education and training gap in LGBTQ + mental health for multidisciplinary mental health care providers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aimed to evaluate patient and provider experiences with telemental health (TMH) at an academic outpatient psychiatry department in New York City during the first wave of the COVID-19 pandemic., Methods: Patients and providers completed online surveys evaluating their experience with TMH during the first wave of the COVID-19 pandemic. Surveys were distributed to 1,178 patients and 287 providers from July 2020 through October 2020., Results: 42.5% of providers and 21% of patients responded to the survey. The majority of patient and provider respondents rated the quality of phone and video visits as "equally good" or "somewhat worse" than in-person visits, while the majority of respondents were "somewhat satisfied" or "very satisfied" with video visits. Patients and providers preferred a hybrid model for future care. Common barriers to TMH included privacy, technical difficulties, and wi-fi access., Conclusions: Patients and providers appeared willing to exchange some degree of quality for satisfaction with TMH. This study did not demonstrate with statistical significance any specific patient populations that would benefit more or less from TMH, suggesting that TMH may be a successful model for diverse patient populations. Our results suggest that providers, payors, and regulators should facilitate hybrid care delivery models that incorporate TMH beyond the pandemic., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: Infantile Caffey disease is a rare disorder characterized by acute inflammation with subperiosteal new bone formation, associated with fever, pain, and swelling of the overlying soft tissue. Symptoms arise within the first weeks after birth and spontaneously resolve before the age of two years. Many, but not all, affected individuals carry the heterozygous pathogenic COL1A1 variant (c.3040C>T, p.(Arg1014Cys))., Methods: We sequenced COL1A1 in 28 families with a suspicion of Caffey disease and performed ultrastructural, immunocytochemical, and biochemical collagen studies on patient skin biopsies., Results: We identified the p.(Arg1014Cys) variant in 23 families and discovered a novel heterozygous pathogenic COL1A1 variant (c.2752C>T, p.(Arg918Cys)) in five. Both arginine to cysteine substitutions are located in the triple helical domain of the proα1(I) procollagen chain. Dermal fibroblasts (one patient with p.(Arg1014Cys) and one with p.(Arg918Cys)) produced molecules with disulfide-linked proα1(I) chains, which were secreted only with p.(Arg1014Cys). No intracellular accumulation of type I procollagen was detected. The dermis revealed mild ultrastructural abnormalities in collagen fibril diameter and packing., Conclusion: The discovery of this novel pathogenic variant expands the limited spectrum of arginine to cysteine substitutions in type I procollagen. Furthermore, it confirms allelic heterogeneity in Caffey disease and impacts its molecular confirmation., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p < .0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p < .0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population., (© 2019 The Authors. Human Mutation Published by Wiley Periodicals, Inc.)

Background: Safety plans are recommended as tools to mitigate suicide risk; however, their effectiveness remains unclear., Aim: To evaluate the impact of safety plans on patient care at an outpatient mental health clinic., Method: In this retrospective chart review, patients' treatment engagement, health-care utilization, and risk behaviors were measured. Patients served as their own historical controls, and we compared outcomes in the 6 months before and 6 months after creation of safety plans., Results: In all, 48 patient charts were identified. Hospitalizations were significantly reduced and use of crisis calls significantly increased after implementation of safety plans. There were five suicide attempts before safety plan completion and one after, representing a trend toward statistical significance. Outpatient encounters increased by 18%, missed appointments increased by 34%, psychiatric emergency room visits decreased by 47%, and a 69% reduction in inpatient hospital days was observed, all trending toward statistical significance. No differences were seen in episodes of violence or self-injurious behavior., Limitations: The study sample was small and there was a lack of randomization., Conclusion: Results suggest that safety plans can lead to improvements in utilization of care and patient engagement. Further research is needed to better understand the clinical impact of safety plans on high-risk patients.

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000-3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons-Leu844, Cys845, Ala846, Leu847, and Gly848-located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844-848 exists and will be valuable in the management and genetic counseling of a significant number of individuals., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function.

Aicardi-Goutières syndrome (AGS) is classically characterized by early-onset encephalopathy. However, in some cases, the presenting symptom of concern may actually be cutaneous rather than neurological, leading to the misdiagnosis of the condition. We report the case of three teenage siblings who presented with a lifetime history of chilblain lesions, only one of whom had notable neurologic deficits. Additional findings included acrocyanosis, Raynaud's phenomenon, low-pitch hoarse voice, headache, and arthritis. They were found to have two pathogenic sequence variants in the SAMHD1 gene: a c.602T>A substitution resulting in p.Ile201Asn protein change, previously reported as a pathogenic mutation, as well as a deletion c.719delT which has not been previously reported but results in a predicted pathogenic frame shift mutation. It is important to consider the diagnosis of AGS in patients and families with chilblain lesions in the presence of unexplained neurologic and rheumatic symptoms. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily A-like 1 (SMARCAL1) gene. Changes in gene expression underlie the arteriosclerosis and T-cell immunodeficiency of SIOD; therefore, we hypothesized that SMARCAL1 deficiency causes the focal segmental glomerulosclerosis (FSGS) of SIOD by altering renal gene expression. We tested this hypothesis by gene expression analysis of an SIOD patient kidney and verified these findings through immunofluorescent analysis in additional SIOD patients and a genetic interaction analysis in Drosophila., Results: We found increased expression of components and targets of the Wnt and Notch signaling pathways in the SIOD patient kidney, increased levels of unphosphorylated β-catenin and Notch1 intracellular domain in the glomeruli of most SIOD patient kidneys, and genetic interaction between the Drosophila SMARCAL1 homologue Marcal1 and genes of the Wnt and Notch signaling pathways., Conclusions: We conclude that increased Wnt and Notch activity result from SMARCAL1 deficiency and, as established causes of FSGS, contribute to the renal disease of most SIOD patients. This further clarifies the pathogenesis of SIOD and will hopefully direct potential therapeutic approaches for SIOD patients.

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients., (© 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.)

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections., (© 2013 Wiley Periodicals, Inc.)