Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as "Nasu-Hakola disease," is a globally distributed recessively inherited disease leading to death during the 5th decade of life and is characterized by early-onset progressive dementia and bone cysts. Elsewhere, we have identified PLOSL mutations in TYROBP (DAP12), which codes for a membrane receptor component in natural-killer and myeloid cells, and also have identified genetic heterogeneity in PLOSL, with some patients carrying no mutations in TYROBP. Here we complete the molecular pathology of PLOSL by identifying TREM2 as the second PLOSL gene. TREM2 forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. Patients with PLOSL have no defects in cell-mediated immunity, suggesting a remarkable capacity of the human immune system to compensate for the inactive TYROBP-mediated activation pathway. Our data imply that the TYROBP-mediated signaling pathway plays a significant role in human brain and bone tissue and provide an interesting example of how mutations in two different subunits of a multisubunit receptor complex result in an identical human disease phenotype.

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Multimedia in assessing clinical decision-making skills (CDMS) has been poorly studied, particularly in comparison to traditional text-based assessments. The literature suggests multimedia is more difficult for trainees. We hypothesize that pediatric residents score lower in diagnostic skill when clinical vignettes use multimedia rather than text for patient findings. A standardized method was developed to write text-based questions from 60 high-resolution, quality multimedia; a series of expert panels selected 40 questions with both a multimedia and text-based counterpart, and two online tests were developed. Each test featured 40 identical questions with reciprocal and alternating modality (multimedia vs. text). Pediatric residents and rising 4th year medical students (MS-IV) at a single residency were randomized to complete either test stratified by postgraduate training year (PGY). A mixed between-within subjects ANOVA analyzed differences in score due to modality and PGY. Secondary analyses ascertained modality effect in dermatology and respiratory questions using Mann-Whitney U tests, and correlations on test performance to In-service Training Exam (ITE) scores using Spearman rank. Eighty-eight residents and rising interns completed the study. Overall multimedia scores were lower than text-based scores (p = 0.047, η = 0.04), with highest disparity in rising interns (MS-IV); however, PGY had a greater effect on scores (p = 0.001, η = 0.16). Respiratory questions were not significantly lower with multimedia (n = 9, median 0.71 vs. 0.86, p = 0.09) nor dermatology questions (n = 13, p = 0.41). ITEs correlated significantly with text-based scores (ρ = 0.23-0.25, p = 0.04-0.06) but not with multimedia scores. In physician trainees with less clinical experience, multimedia-based case vignettes are associated with significantly lower scores. These results help shed light on the role of multimedia versus text-based information in CDMS, particularly in less experienced clinicians.

Chylothorax is a rare but dangerous cause of respiratory failure in the pediatric population. It most commonly presents after cardiac surgery or, alternatively, due to retrograde pressure on the thoracic duct from narrowing or obstruction in the innominate vein due to thrombus or neoplasm. We observed an unusual presentation of chylothorax in an otherwise healthy 3-month-old infant with congenital superior vena cava stenosis leading to acute respiratory collapse. After initially not responding to medical therapy, the patient was successfully treated with an intravascular stent.

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