Acoustics reflex abnormalities in auditory processing disorder

Introduction: The acoustic reflex threshold is defined as the lowest sound intensity capable of starting the middle ear protection mechanism due to intense sounds (Metz, 1952; Jerger, 1970), being necessary the structural and functional integrity of the periferic and central auditory system. These structures are also responsable for the central processing of auditory information. Aim: We intend to verify whether acoustic reflex abnormalities can also appear in auditory processing (AP) disorders, resulting in symptoms related to speech and language disorders. Study design: Prospective randomized. Material and method: Data were analyzed from one hundred AP assessments, using Pereira (1997) method. Patients, male and female, with ages ranging from 07 to 18 years, had normal hearing thresholds and normal tympanograms patterns. The difference between the acoustic reflex and hearing thresholds defined the acoustic reflex level (ARL), considered normal between 70-90dB and altered when above of this range or when absent in one or more frequencies (Carvallo, 1996; 1997; Metz, 1952). Results: Disorders of AP were found in 97% of the patients. In this group, 62% showed ARL abnormalities, being statistically significant. Furthermore, patients with AP disorders showed ARL alterations, more frequently on severe degree disorders, on patients with combined auditory gnosis impairments and on patients with more than one auditory ability altered. Conclusion: Patients with acoustic reflex alterations and normal audiometry should perform the AP assessment, as these symptoms could unmask pathologies of the central nervous system.Introdução: O limiar do reflexo acústico corresponde à menor intensidade de um som capaz de desencadear o mecanismo de proteção da orelha média frente a sons intensos (Metz, 1952; Jerger, 1970), sendo necessária a integridade estrutural e funcional do sistema auditivo periférico e central em nível de tronco encefálico. Algumas dessas estruturas são também responsáveis pelo processamento central da informação auditiva. Objetivo: Procuramos verificar se alterações do reflexo acústico também estariam presentes na Desordem do Processamento Auditivo Central (DPA), levando a queixas relacionadas aos distúrbios da comunicação. Forma de estudo: Prospectivo randomizado. Material e método: Foram analisados cem protocolos de avaliações do Processamento Auditivo Central (PAC), realizadas segundo Pereira (1997), de indivíduos dos sexos masculino e feminino, de 7 a 18 anos, com limiares de audibilidade normais e timpanograma tipo A. A diferença entre os limiares do reflexo acústico e os de audibilidade forneceu os níveis de reflexos acústicos (NRA), considerados normais entre 70-90dB e alterados quando acima deste intervalo ou quando ocorreu ausência em uma ou mais freqüências (Carvallo, 1996; 1997; Metz, 1952). Resultados: Das crianças avaliadas 97% apresentaram algum tipo de DPA. Destas, 62% tiveram NRA alterados, numa relação estatisticamente significante. Além disso, pacientes com DPA mostraram NRA alterados, mais freqüentemente, nas desordens de grau severo, naquelas com prejuízos gnósicos auditivos combinados e naquelas com mais de uma habilidade auditiva alterada. Conclusão: Assim, indivíduos com alterações no reflexo acústico e sem alterações audiométricas devem submeter-se a provas de PAC, já que esses sintomas podem ser manifestações patológicas do sistema nervoso central.UNIFESP-EPM OtorrinolaringologiaUNIFESP-EPMUNIFESP, EPM, OtorrinolaringologiaUNIFESP, EPMSciEL

Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner.

Oncogene-induced replication stress is a crucial driver of genomic instability and one of the key events contributing to the onset and evolution of cancer. Despite its critical role in cancer, the mechanisms that generate oncogene-induced replication stress remain not fully understood. Here, we report that an oncogenic c-Myc-dependent increase in cohesins on DNA contributes to the induction of replication stress. Accumulation of cohesins on chromatin is not sufficient to cause replication stress, but also requires cohesins to accumulate at specific sites in a CTCF-dependent manner. We propose that the increased accumulation of cohesins at CTCF site interferes with the progression of replication forks, contributing to oncogene-induced replication stress. This is different from, and independent of, previously suggested mechanisms of oncogene-induced replication stress. This, together with the reported protective role of cohesins in preventing replication stress-induced DNA damage, supports a double-edge involvement of cohesins in causing and tolerating oncogene-induced replication stress

Active growth signaling promotes senescence and cancer cell sensitivity to CDK7 inhibition

Tumor growth is driven by continued cellular growth and proliferation. Cyclin-dependent kinase 7’s (CDK7) role in activating mitotic CDKs and global gene expression makes it therefore an attractive target for cancer therapies. However, what makes cancer cells particularly sensitive to CDK7 inhibition (CDK7i) remains unclear. Here, we address this question. We show that CDK7i, by samuraciclib, induces a permanent cell-cycle exit, known as senescence, without promoting DNA damage signaling or cell death. A chemogenetic genome-wide CRISPR knockout screen identified that active mTOR (mammalian target of rapamycin) signaling promotes samuraciclib-induced senescence. mTOR inhibition decreases samuraciclib sensitivity, and increased mTOR-dependent growth signaling correlates with sensitivity in cancer cell lines. Reverting a growth-promoting mutation in PIK3CA to wild type decreases sensitivity to CDK7i. Our work establishes that enhanced growth alone promotes CDK7i sensitivity, providing an explanation for why some cancers are more sensitive to CDK inhibition than normally growing cells

Changes in Glucose and Glutamine Lymphocyte Metabolisms Induced by Type I Interferon α

In lymphocytes (LY), the well-documented antiproliferative effects of IFN-α are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-α, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFNα also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFNα are associated with a reduction in glucose and glutamine metabolisms

Caracterização clínica e histopatológica da adenite sebácea em diferentes fases

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