Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics

Thermal behavior, spectroscopic studies and free radical scavenging potential of some mefenamate trivalent lanthanides (Sm, Eu, Gd, Tb and Dy)

Lanthanide Mefenamate compounds were prepared in solid state. TG-DSC coupled to FTIR, elemental analysis, complexometry with EDTA, X-ray powder diffractometry, evaluation of scavenging free radical activity with DPPH (2,2-diphenyl-1-picryl-hydrazine), and a complete spectroscopic study in the ultraviolet, visible, near-, and middle-infrared regions were realized to obtain some physicochemical properties of the synthesized compounds. The thermal stability, minimum formula, thermal behavior and intermediate compounds were indicated by thermoanalytical results. Furthermore, vibrational spectroscopy data suggests that the complexes are binuclear and two modes of coordination are presented. The DR spectra could be reveal the presence of a large ligand-to-metal charge transfer band in the europium mefenamate. This compound also indicated the higher antioxidant activity with DPPH (77.03% at 200 μg L−1).6517382CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçãoSem informaçã

Thermal Behavior, Spectroscopic Studies And Free Radical Scavenging Potential Of Some Mefenamate Trivalent Lanthanides (sm, Eu, Gd, Tb And Dy)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Lanthanide Mefenamate compounds were prepared in solid state. TG-DSC coupled to FTIR, elemental analysis, complexometry with EDTA, X-ray powder diffractometry, evaluation of scavenging free radical activity with DPPH (2,2-diphenyl-1-picryl-hydrazine), and a complete spectroscopic study in the ultraviolet, visible, near-, and middle-infrared regions were realized to obtain some physicochemical properties of the synthesized compounds. The thermal stability, minimum formula, thermal behavior and intermediate compounds were indicated by thermoanalytical results. Furthermore, vibrational spectroscopy data suggests that the complexes are binuclear and two modes of coordination are presented. The DR spectra could be reveal the presence of a large ligand-to-metal charge transfer band in the europium mefenamate. This compound also indicated the higher antioxidant activity with DPPH (77.03% at 200 μg L−1). © 2017 Elsevier B.V.6517382CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP, Fundação de Amparo à Pesquisa do Estado de São PauloCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life

Introduction: Epilepsy, which is present in 0.5–1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. Methods: Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients’ medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. Results: We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1–144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. Conclusions: VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life. Resumen: Introducción: La epilepsia es uno de los trastornos neurológicos más frecuentes de la infancia, presentándose en un 0,5–1%. Aproximadamente un 20–30% de los pacientes son farmacorresistentes. El objetivo de este trabajo es describir en 30 pacientes el impacto sobre las crisis y la calidad de vida del estimulador del nervio vago (ENV). Métodos: Se trata de un estudio descriptivo, retrospectivo, mediante revisión de las historias clínicas de todos los pacientes a quienes se les colocó el ENV entre el 2008 y 2013 en nuestro centro. La calidad de vida fue valorada mediante la escala de calidad de vida en el niño con epilepsia (CAVE), obtenida por medio de una entrevista telefónica. Resultados: Se incluyeron 19 niños (64%) y 11 niñas (36%) con una mediana de comienzo de las crisis de 21 meses (1–144 meses). La edad promedio de colocación del ENV fue de 11,89 años. El tiempo de seguimiento fue de 6–36 meses. A los 6 meses la reducción de las crisis en promedio fue del 38%, a los 12 meses del 43%, a los 24 meses del 42% y a los 36 meses del 54%. De todos los pacientes evaluados al menos un 50% se catalogaron como respondedores. Según la CAVE un 54% de las familias encontró el efecto del ENV como bueno o muy bueno y un 39% como regular. Conclusiones: El ENV es un tratamiento paliativo, generalmente bien tolerado, parcialmente efectivo para el control de la epilepsia refractaria en pediatría y con repercusiones positivas sobre la calidad de vida. Keywords: Drug-resistant epilepsy, Epilepsy treatment, Vagal nerve stimulator, Quality of life in children with epilepsy scale, Palabras clave: Epilepsia refractaria, Tratamiento de epilepsia refractaria, Estimulador nervio vago, Escala de calidad de vida en el niño con epilepsi