Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target.

To identify the risk factors and attributable mortality associated with superinfections in febrile neutropenic patients with hematologic malignancies, we prospectively evaluated 333 episodes of fever and neutropenia by means of univariate and multivariate analyses. Superinfection was defined as any infection either occurring during antibiotic therapy or developing within 1 week after discontinuation of antibiotic therapy. Of 333 episodes, 46 (13.8%) were defined as superinfection; these episodes occurred in 46 patients. The risk factors for superinfection in the multivariate analysis were longer duration of profound neutropenia (P < .0001), lack of use of quinolones as prophylaxis (P < .0001), presence of a central venous catheter (P = .02), and persistence of fever after 3 days of antibiotic therapy (P = .02). The crude mortality rate among patients with superinfection was 48%, and the attributable mortality rate was 24% (95% confidence interval, 3%-45%). Identifying risk factors for superinfections in neutropenic patients might allow clinical practices to reduce the negative impact of this complication.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplastic proliferation with variable clinical behavior caused by the accumulation of CD1a/CD207 histiocytes, associated with a variable number of eosinophils, lymphocytes, plasma cells and multinucleated giant cells, most commonly observed in male children. LCH is uncommon in the head and neck region, occurring as ulcerated and reddened plaques or nodules that cause destruction of adjacent soft tissues and bone. The exact etiology of LCH is still unknown and controversial, with possible etiologic role of viruses, including Epstein-Barr virus (EBV). The aim of this study was to describe the clinicopathologic and immunohistochemical features of patients with LCH of the head and neck region. Clinical data from 19 patients with LCH were obtained from the archives of the Federal University of Rio de Janeiro and the Clinical Head and Neck Center of Guatemala. All cases were submitted to morphological, immunohistochemical analysis with CD1a, CD207, CD3, CD20, CD68, S-100 and Ki-67 and in situ hybridization for EBV. Ten cases were female and 9 male, with mean age of 11.5 years. Fourteen cases were located in the oral cavity, three cases in lymph nodes, and two cases in the scalp. In regard to the oral lesions, 13 cases were intra-osseous with six cases in anterior mandible, five cases in posterior mandible, and two cases in posterior maxilla while one case was located exclusively in the gingiva. The inflammatory pattern showed variation in the number of plasma cells, eosinophils and lymphocytes, while tumor cells were positive for CD1a, S-100 and CD68 in all cases, and positive for CD207 in 18 cases. In situ hybridization for EBV were negative in all cases.

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In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p < 0.001), longer duration of profound (< 100/mm3) neutropenia (p < 0.001), the use of corticosteroids (p < 0.001), gram-positive bacteremia (p = 0.002) and younger age (p = 0.03). In multivariate analysis only recovery of the neutropenia (p < 0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p = 0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.