Valenzuelasmidt3823

INTRODUCTION Alzheimer's disease (AD) is still the fifth leading cause of death and most common dementia worldwide. To date, there is no efficient strategy that can slow down the progression of AD owing to delayed diagnosis and limited therapies. MiR-143-3p is up-regulated in serum of AD patients, yet the exact role it plays in AD pathology is still poorly understood. The aim of this study was to investigate the effect of miR-143-3p on neuronal survival. MATERIAL AND METHODS We induced neuronal differentiation in SH-SY5Y cells using all-trans-retinoic acid (RA), and Aβ1-42 was used to establish the in vitro AD cell model. AZD9291 The expression of tubulin β III and neuregulin-1 (NRG1) was evaluated by immunofluorescence. TUNEL assay was performed to assess cell apoptosis. Cell viability was evaluated using the Cell Counting Kit-8 assay. The binding interaction between miR-143-3p and NRG1 was verified using the luciferase reporter assay. RESULTS Typical neuronal-like axons were observed in RA-induced SH-SY5Y cells, followed by increased tubulin β III. A dramatically increased apoptotic rate and reduced cell viability were observed in the AD cell model. Then we silenced the miR-143-3p expression, and Aβ1-42 induced cell apoptosis was alleviated after miR-143-3p inhibition, accompanied by decreased cleaved caspase-3 and cleaved caspase-9 levels. Additionally, NRG1 was confirmed to be a downstream target of miR-143-3p, increased cell viability and suppressed cell apoptosis after miR-143-3p inhibition was abolished by NRG1 knockdown. CONCLUSIONS Our findings reveal that miR-143-3p inhibition promotes neuronal survival in an in vitro cell model via targeting NRG1, and the miR-143-3p/NRG1 axis is a potential therapeutic target and promising biomarker for AD treatment.Alzheimer's disease neuropathologic change (ADNC) in the form of β-amyloid (Aβ) deposits occurs not only in Alzheimer's disease (AD) and Down's syndrome (DS) but also as a 'co-pathology' in several disorders including dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). To determine whether cortical laminar degeneration, as measured by Aβ deposition, is similar in different disorders, changes in density of the diffuse, primitive, and classic morphological subtypes of Aβ deposit were studied across all cortical layers in the frontal and temporal cortex in AD, DS, DLB, CBD, and CTE using quantitative analysis and polynomial curve fitting. In AD, CTE, and DLB, the diffuse Aβ deposits were distributed most frequently in the upper cortical layers, distribution being more variable in DS and CBD. In all disorders, the primitive Aβ deposits were distributed primarily in the upper layers, but in DLB, a bimodal distribution with peaks of density in upper and lower layers was evident in some gyri. The distribution of the classic deposits varied both within and among disorders. The many similarities in laminar distribution among disorders suggest common patterns of cortical degeneration. Where differences occur, they may reflect variations in the 'prion-like' propagation of Aβ along anatomical pathways in the different disorders.Aortic dissection is a complex pathology that carries significant morbidity and mortality if not treated in a timely fashion. While the open repair remains the gold standard treatment for patients with acute type A dissection, ascending aortic replacement is associated with high incidence of arch and descending thoracic aorta residual false lumen patency and aneurysmal degeneration. Multiple approaches have been used over the decades to address aneurysmal degeneration in the arch and thoracoabdominal aorta. This article summarizes anatomical requirements for total endovascular repair of aortic arch and TAAAs using fenestrated and branched endografts.BACKGROUND We aim to reflect on our experience utilising the Frozen Elephant Trunk (FET) and straight vascular prostheses. METHODS 300 patients from 2005 to 2018 were identified from our prospectively collected data stratifying the patients who underwent aortic surgery including the arch and distal aortic stream. We examined the pre-operative and operative characteristics of these patients along with in-hospital outcomes and follow-up survival. Continuous and categorical variables were analysed using two-sided unpaired t-test and Fischer's exact test, respectively. Kaplan Meier analysis was used to evaluate survival. RESULTS 300 patients (mean age 59) underwent one stage surgery utilizing our FET for acute aortic dissection (AAD - 55%), chronic aortic dissection (CAD - 23%) and thoracic aortic aneurysm (TAA - 22%). 30-day mortality was 12%, highest amongst the AAD group (12.8%). Neurological deficit stratified into permanent stoke and paraplegia was 7% and 2% respectively.Freedom from aortic related death at 10 years was 91%. Survival probability at 5 years for AAD, CAD & TAA was 91%, 98% & 92% respectively. Freedom from re-intervention in AAD proximal repair vs. FET was 68% vs 87% at 5 years and 48% vs 74% at 10 years respectively. Patients were separated according to distal anastomosis level in Zone 2 (Z2, 237) and Zone 3 (Z3, 105). Conceptual Zone 2 versus Zone 3 aortic arch replacement survival analysis at 5 years was Z2 - 75% vs Z3 - 60% (p=0.034); and at 8 years was Z2 - 74% vsZ3 - 52% (p=0.018) (figure 3, A). CONCLUSIONS Frozen elephant trunk using EVITA Hybrid Open Plus stent graft and other devices in the family of device technology attain optimal outcomes to treat complex thoracic aortic lesions in elective and non-elective settings.Acute Type A aortic dissection remains one of the most challenging conditions in aortic surgery. Despite the advancements in the field the mortality rate still remains high. Though there is a general consensus that the ascending aorta should be replaced, the distal extension of the surgery still remains a controversy. Few surgeons argue for a conservative approach to reduce operative and postoperative morbidity while others considering the problems associated with "downstream problems" support an aggressive approach including a frozen elephant trunk. The cohort in the Indian subcontinent and APAC is far different from the western world. Many factors determine the decision for surgery apart from the pathology of the disease. Economy, availability of the suitable prosthesis, the experience of the surgeon, ease of access to the medical facility all contribute to the decision making to treat acute type A dissection.