Scale of Auditory Behaviors e testes auditivos comportamentais para avaliação do processamento auditivo em crianças falantes do português europeu

PURPOSE: The objective of this research was to assess the auditory abilities of Portuguese children and compare such abilities to the score of the Scale of Auditory Behaviors (SAB). METHODS: Fifty-one children were evaluated with audiometry, speech audiometry, acoustic immittance measures, and eight behavioral tests involving dichotic listening, monotic listening, temporal processing, and sound localization. Their parents filled in the SAB questionnaire adapted to European A. SAB scores and auditory tests scores were submitted to Pearson's correlation coefficient. RESULTS: There is significant correlation between the score on SAB questionnaire and the auditory processing tests. The greatest coefficient was observed in temporal processing test (p=0.000). CONCLUSION: There was correlation between the score of SAB and the performance in auditory processing tests, suggesting that the SAB may be used for auditory processing screening.OBJETIVO: Investigar as habilidades auditivas de crianças portuguesas e verificar se há correlação entre aquelas e o escore do Scale of Auditory Behaviors (SAB). MÉTODOS: Todas as crianças foram submetidas a audiometria tonal, logoaudiometria, medidas de imitância acústica e oito testes comportamentais do processamento auditivo, envolvendo tarefas de escuta dicótica, escuta monótica, processamento temporal e localização sonora. Os pais das 51 crianças portuguesas avaliadas preencheram o questionário SAB adaptado ao português europeu. Foram calculados os valores do coeficiente de correlação de Pearson entre os escores obtidos no questionário e os dos testes do processamento auditivo. RESULTADOS: Observou-se correlação significativa entre o escore do questionário e o dos testes comportamentais, tendo a maior sido observada nos testes relacionados ao processamento temporal (p=0,000). CONCLUSÃO: Houve correlação entre o escore da SAB e os resultados obtidos nos testes auditivos comportamentais em crianças portuguesas, sugerindo que este questionário pode ser utilizado em triagem do processamento auditivo.CIEC – Research Centre on Child Studies, UM (FCT R&D 317

Atypical propylthiouracil-induced ANCA-positive vasculitis: report of a case with unusual clinical and histopathologic findings

The side effects of propylthiouracil, including cytopenia and vasculitis, are well established.  We present an interesting case in which cytopenia and cutaneous vasculopathy occurred concomitantly in a critically ill patient.  The patient was initially treated for suspected infection until dermatologic and rheumatologic workup revealed ANCA-positivity and vasculopathy on histopathology, most consistent with an atypical presentation of ANCA-positive vasculitis.  Upon initiation of immunosuppressive therapy, the patient’s condition rapidly improved emphasizing the importance of early recognition of this condition

REV-ERBα mediates complement expression and diurnal regulation of microglial synaptic phagocytosis

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, includin

Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration

Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. However, the mechanistic links between ether phospholipids, blood pressure, and neurodegeneration are not fully understood. Here, we show that endothelium-derived ether phospholipids affect blood pressure, behavior, and neurodegeneration in mice. In young adult mice, inducible endothelial-specific disruption of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, unexpectedly decreased circulating plasmalogens. PexRAP endothelial knockout (PEKO) mice responded normally to hindlimb ischemia but had lower blood pressure and increased plasma renin activity. In PEKO as compared with control mice, tyrosine hydroxylase was decreased in the locus coeruleus, which maintains blood pressure and arousal. PEKO mice moved less, slept more, and had impaired attention to and recall of environmental events as well as mild spatial memory deficits. In PEKO hippocampus, gliosis was increased, and a plasmalogen associated with memory was decreased. Despite lower blood pressure, PEKO mice had generally normal homotopic functional connectivity by optical neuroimaging of the cerebral cortex. Decreased glycogen synthase kinase-3 phosphorylation, a marker of neurodegeneration, was detected in PEKO cerebral cortex. In a co-culture system, PexRAP knockdown in brain endothelial cells decreased glycogen synthase kinase-3 phosphorylation in co-cultured astrocytes that was rescued by incubation with the ether lipid alkylglycerol. Taken together, our findings suggest that endothelium-derived ether lipids mediate several biological processes and may also confer neuroprotection in mice

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration

Pitfalls in the diagnosis of acoustic neuroma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71894/1/j.1365-2273.1984.tb01490.x.pd

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2- dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods: Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤ 300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results: 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions: The endogenous detection of these electro.©2014 Cipollina et al

Endogenous Signaling by Omega-3 Docosahexaenoic Acid-derived Mediators Sustains Homeostatic Synaptic and Circuitry Integrity

The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This phenomenon began to be clarified by the discovery of neuroprotectin D1 (NPD1), the first-uncovered bioactive docosanoid formed from free DHA through 15-lipoxygenase-1 (15-LOX-1). NPD1 synthesis includes, as agonists, oxidative stress and neurotrophins. The evolving concept is that DHA-derived docosanoids set in motion endogenous signaling to sustain homeostatic synaptic and circuit integrity. NPD1 is anti-inflammatory, displays inflammatory resolving activities, and induces cell survival, which is in contrast to the pro-inflammatory actions of the many of omega-6 fatty acid family members. We highlight here studies relevant to the ability of DHA to sustain neuronal function and protect synapses and circuits in the context of DHA signalolipidomics. DHA signalolipidomics comprises the integration of the cellular/tissue mechanism of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains containing DHA phospholipids, and the precise cellular and molecular events revealed by the uncovering of signaling pathways regulated by docosanoids endowed with prohomeostatic and cell survival bioactivity. Therefore, this approach offers emerging targets for prevention, pharmaceutical intervention, and clinical translation involving DHA-mediated signaling

Mapping the multicausality of Alzheimer's disease through group model building.

Alzheimer's disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellular to psychosocial scales in sporadic AD. We report on the first systemic causal loop diagram (CLD) for AD, which is the result of an interdisciplinary group model building (GMB) process. The GMB was based on the input of experts from multiple domains and all proposed mechanisms were supported by scientific literature. The CLD elucidates interaction and feedback mechanisms that contribute to cognitive decline from midlife onward as described by the experts. As an immediate outcome, we observed several non-trivial reinforcing feedback loops involving factors at multiple spatial scales, which are rarely considered within the same theoretical framework. We also observed high centrality for modifiable risk factors such as social relationships and physical activity, which suggests they may be promising leverage points for interventions. This illustrates how a CLD from an interdisciplinary GMB process may lead to novel insights into complex disorders. Furthermore, the CLD is the first step in the development of a computational model for simulating the effects of risk factors on AD