The Expression and Roles of Nde1 and Ndel1 in the Adult Mammalian Central Nervous System

Open Access funded by Wellcome Trust Under a Creative Commons license Acknowledgments We thank Prof Angelo Sementilli, Department of Pathology, Universidade Metropolitana de Santos, SP, Brazil, for the human sample collection. This study is funded by Scottish Universities Life Sciences Alliance (HR07019 to S. Shen and C.D. McCaig), Medical Research Scotland (384 FRG to B. Lang, United Kingdom), Tenovus Scotland (G12/25 to B. Lang), Sino-UK Higher Education Research Partnership for PhD Studies (C.D. McCaig and Y.Q. Ding) and Wellcome Trust (WT081633MA-NCE to P.J.A. McCaffery, United Kingdom).Peer reviewedPublisher PD

Transmisión del oleaje en arrecifes artificiales

Los arrecifes artificiales se han empleado como obras de protección playera con éxito en varias partes del mundo. Para aplicarlos es necesario establecer las condiciones de oleaje a que serán sometidos, teniendo como objeto del estudio la obtención de los coeficientes de transmisión como indicador de su eficiencia. El estudio se realizó en el canal angosto con generador hidráulico de oleaje irregular y equipo de medición de oleaje controlados por computadoras, equipo con que cuenta el Laboratorio de Ingeniería Hidráulica de la Escuela Superior de Ingeniería y Arquitectura-Unidad Zacatenco del Instituto Politécnico Nacional de México. Se implementó un modelo físico reducido en el que se construyeron dos secciones de arrecife, y se calcularon los coeficientes de transmisión del oleaje, que se contrastaron con formulaciones presentadas en el estado del arte

Reducción de la socavación local en estribos cortos y verticales de puentes

Se describe un proyecto de investigación, cuyo objetivo fue reducir la profundidad de socavación al pie de estribos cortos y verticales de puentes, mediante un modelo físico reducido se analizó la profundidad de socavación que genera un flujo de agua, en sistema formado por un estribo de puente corto y vertical y el fondo de arena de un canal del laboratorio de ingeniería hidráulica de la ESIA unidad Zacatenco; al estribo se le cambiaba su geometría en los ensayos (con alerones laterales a 45, 30 y 20º), para determinar experimentalmente su influencia en la erosión local que generó, bajo ciertas condiciones de flujo; y así en base a ensayo–error, reducir la erosión local. Se logró reducir la profundidad de socavación generada por el estribo original en un 98 %

Almost sure stability of discrete-time Markov Jump Linear Systems

This paper deals with transient analysis and almost sure stability for discrete-time Markov Jump Linear System (MJLS). The expectation of sojourn time and activation number of any mode, and switching number between any two modes of discrete-time MJLS are presented firstly. Then a result on transient behavior analysis of discrete-time MJLS is given. Finally a new deterministically testable condition for the exponential almost sure stability of discrete-time MJLS is proposed

An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly

Asthma in the elderly (>65 yr old) is common and associated with higher morbidity and mortality than asthma in younger patients. The poor outcomes in this group are due, in part, to underdiagnosis and undertreatment. There are a variety of factors related to aging itself that affect the presentation of asthma in the elderly and influence diagnosis and management. Structural changes in the aging lung superimposed on structural changes due to asthma itself can worsen the disease and physiologic function. Changes in the aging immune system influence the cellular composition and function in asthmatic airways. These processes and differences from younger individuals with asthma are not well understood. Phenotypes of asthma in the elderly have not been clearly delineated, but it is likely that age of onset and overlap with chronic obstructive pulmonary disease impact disease characteristics. Physiologic tests and biomarkers used to diagnose and follow asthma in the elderly are generally similar to testing in younger individuals; however, whether they should be modified in aging has not been established. Confounding influences, such as comorbidities (increasing the risk of polypharmacy), impaired cognition and motor skills, psychosocial effects of aging, and age-related adverse effects of medications, impact both diagnosis and treatment of asthma in the elderly. Future efforts to understand asthma in the elderly must include geriatric-specific methodology to diagnose, characterize, monitor, and treat their disease

Effects of low-intensity electrical stimulation and adipose derived stem cells transplantation on the time-domain analysis-based electromyographic signals in dogs with SCI

The application of low-intensity electrical stimulation (LIES) to neural tissue increases neurochemical factors responsible for regeneration as nerve growth factor. Stem cell (SC) therapy for patients with Spinal cord injury (SCI) promote some increase functional improvement.ObjectiveInvestigate the electromyographic response in paraplegic dogs undergoing LIES and SC transplantation.Methods27 dogs paraplegics with SCI were divided into three groups with different types of therapy. GADSC: two SC transplants (n = 9); GLIES: LIES (n = 8); GCOMB: two SC transplants and LIES (n = 10). Adipose derived mesenchymal stem cells (ADSCs) were transplanted by lumbar puncture in the amount of 1.2 × 106 cells/50 μL. Acupuncture needles positioned in the interspinous space were used for stimulation. The electrical stimulation was applied with a mean voltage ∼30 mV and four consecutive modulated frequencies (5 Hz, 10 Hz, 15 Hz and 20 Hz) within 5 min each. The patients motor performance was evaluated before (Pre) the procedure and after 30 (Post30) and 60 (Post60) days, from electromyography root mean square (EMGRMS) registered with subcutaneous electrodes in the vastus lateralis muscle, while the animals were in quadrupedal position.ResultsAll three groups showed a significant intra-group increase of EMGRMS (Pre vs. Post30 or Pre vs. Post60). However, there were no statistically significant differences between Post30 and Post60. The inter-group test (GADSC X GLIES X GCOMB) did not present significance when compared the instants Pre (p = 0.34), Post30 (p = 0.78) and Post60 (p = 0.64).ConclusionSome dogs recovered motor activity, expressed by the EMGRMS, in all groups, in pre vs. post (30 or 60 days) comparisons.This is the peer-reviewed version of the article: Krueger, E., Magri, L.M.S., Botelho, A.S., Bach, F.S., Rebellato, C.L.K., Fracaro, L., Fragoso, F.Y.I., Villanova, J.A., Brofman, P.R.S., Popović-Maneski, L., 2019. Effects of low-intensity electrical stimulation and adipose derived stem cells transplantation on the time-domain analysis-based electromyographic signals in dogs with SCI. Neuroscience Letters 696, 38–45. [https://doi.org/10.1016/j.neulet.2018.12.004]Published version: [https://hdl.handle.net/21.15107/rcub_dais_4595

A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol

© 2020, The Author(s). Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. Methods: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. Discussion: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. Trial registration: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020)

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al