Direct access endoscopy in a Brazilian public healthcare facility: comparable results with specialist referred endoscopy.

BACKGROUND: Direct access endoscopy (DAE) is the procedure performed without the pre-evaluation of the patient by a specialist. It is widely available in many medical services around the world, but there is lack of data about this strategy in the setting of the public health system in Brazil. Therefore, the aim of this study is to compare the main endoscopic findings of upper gastrointestinal endoscopy requested through DAE and by specialists. METHODS: Longitudinal, retrospective single center study in patients who underwent upper digestive endoscopy in a public healthcare facility at the southern region of the state of Mato Grosso, Brazil, from August 2011 to December 2018. Age, gender, modality of endoscopy request (DAE or endoscopy requested by specialists), and endoscopic findings were analyzed. RESULTS: A total of 2810 patients were included. Most of them were female 65.23% (1833), mean age was 47.36 years, and 50.71% of the exams (1425) were DAE. Only 4.62% of the exams had normal reports. The most frequent endoscopic findings were gastritis (91.99%), bulboduodenitis (43.59%) and reflux esophagitis (14.76%). Patients who underwent endoscopy requested by specialists were older (50.25 ± 16.57 vs. 44.55 ± 16.31 years, p < .0001) and more frequently men (36.61 vs. 32.98%, p = .0437) in comparison to DAE. However, endoscopic findings were similar in both groups. CONCLUSION: This study shows that direct access upper endoscopy had comparable results to specialist requested endoscopy in a public healthcare facility in the southern region of the state of Mato Grosso, Brazil.

The Co-chaperone BAG2 Mediates Cold-Induced Accumulation of Phosphorylated Tau in SH-SY5Y Cells.

Inclusions of phosphorylated tau (p-tau) are a hallmark of many neurodegenerative disorders classified as "tauopathy," of which Alzheimer's disease is the most prevalent form. Dysregulation of tau phosphorylation disrupts neuron structure and function, and hyperphosphorylated tau aggregates to form neurotoxic inclusions. The abundance of ubiquitin in tau inclusions suggests a defect in ubiquitin-mediated tau protein degradation by the proteasome. Under the temperature of 37 °C, the co-chaperone BAG2 protein targets phosphorylated tau for degradation via by a more-efficient, ubiquitin-independent pathway. In both in vivo and in vitro studies, cold exposure induces the accumulation of phosphorylated tau protein. The SH-SY5Y cell line differentiates into neuron-like cells on treatment with retinoic acid and is an established model for research on the effects of cold on tau phosphorylation. The aim of the present study was to investigate whether BAG2 mediates the cold-induced accumulation of phosphorylated tau protein. Our findings show that cold exposure causes a decrease in BAG2 expression in undifferentiated cells. Conversely, BAG2 expression is increased in differentiated cells exposed to cold. Further, undifferentiated cells exposed to cold had an increased proportion of p-tau to total tau, suggesting an accumulation of p-tau that is consistent with decreased levels of BAG2. Overexpression of BAG2 in cold-exposed undifferentiated cells restored levels of p-tau to those of 37 °C undifferentiated control. Interestingly, although BAG2 expression increased in differentiated cells, this increase was not accompanied by a decrease in the proportion of p-tau to total tau. Further, overexpression of BAG2 in cold exposed differentiated cells showed no significant difference in p-tau levels compared to 37 °C controls. Taken together, these data show that expression of BAG2 is differently regulated in a differentiation-dependent context. Our results suggest that repression of BAG2 expression or BAG2 activity by cold-sensitive pathways, as modeled in undifferentiated and differentiated cells, respectively, may be a causal factor in the accumulation of cytotoxic hyperphosphorylated tau protein via restriction of BAG2-mediated clearance of cellular p-tau.

Pro-necrotic Activity of Cationic Mastoparan Peptides in Human Glioblastoma Multiforme Cells Via Membranolytic Action.

Glioblastoma multiforme is the most common and lethal malignant brain tumor. Because of its complexity and heterogeneity, this tumor has become resistant to conventional therapies and the available treatment produces multiple side effects. Here, using multiple experimental approaches, we demonstrate that three mastoparan peptides-Polybia-MP1, Mastoparan X, and HR1-from solitary wasp venom exhibit potent anticancer activity toward human glioblastoma multiforme cells. Importantly, the antiglioblastoma action of mastoparan peptides occurs by membranolytic activity, leading to necrosis. Our data also suggest a direct relation between mastoparan membranolytic potency and the presence of negatively charged phospholipids like phosphatidylserine. Collectively, these data may warrant additional studies for mastoparan peptides as new agents for the treatment of glioblastoma multiforme brain tumor.

Thiamine deficiency during pregnancy leads to cerebellar neuronal death in rat offspring: role of voltage-dependent K+ channels.

Oxidative stress, selective neuronal loss, and diminished activity of thiamine-dependent enzymes play a role in many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. To further understand the major implications of thiamine deficiency (TD) in neuronal death, we induced TD during pregnancy and evaluated the effects on the offspring. The body and brain weights of pups from thiamine-deficient dams were significantly smaller than normal. Loss of neuronal viability was examined by trypan blue exclusion assay, and demonstrated increased cytotoxicity in primary cultures of TD neurons. Additionally, cerebellar cultures were exposed to thiamine-free cell culture medium to better explore the effects of thiamine withdrawal. Alterations in potassium current has previously been associated with the development of cell death. In this study, we examined the TD effects on delayed rectifier and A-type K+ channels, two well-known voltage-activated K+ channels involved in the regulation of action potential firing in cerebellar granule neurons. Current recordings were performed in cultured rat cerebellar granule neurons at day 7, using the whole-cell voltage-clamp technique. Our data demonstrate that thiamine deficiency provoked a significant decrease in the voltage-dependent K+ membrane conductance. Finally, TD markedly depressed the transient A-type K+ currents.