Roadmap for stroke: Challenging the role of the neuronal extracellular matrix

Stroke is a major challenge in modern medicine and understanding the role of the neuronal extracellular matrix (NECM) in its pathophysiology is fundamental for promoting brain repair. Currently, stroke research is focused on the neurovascular unit (NVU). Impairment of the NVU leads to neuronal loss through post-ischemic and reperfusion injuries, as well as coagulatory and inflammatory processes. The ictal core is produced in a few minutes by the high metabolic demand of the central nervous system. Uncontrolled or prolonged inflammatory response is characterized by leukocyte infiltration of the injured site that is limited by astroglial reaction. The metabolic failure reshapes the NECM through matrix metalloproteinases (MMPs) and novel deposition of structural proteins continues within months of the acute event. These maladaptive reparative processes are responsible for the neurological clinical phenotype. In this review, we aim to provide a systems biology approach to stroke pathophysiology, relating the injury to the NVU with the pervasive metabolic failure, inflammatory response and modifications of the NECM. The available data will be used to build a protein–protein interaction (PPI) map starting with 38 proteins involved in stroke pathophysiology, taking into account the timeline of damage and the co-expression scores of their RNA patterns The application of the proposed network could lead to a more accurate design of translational experiments aiming at improving both the therapy and the rehabilitation processes

Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its SurgicalImplication

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients' prognosis and correct surgical/radiotherapy planning

Altered Spinal Homeostasis and Maladaptive Plasticity in GFAP Null Mice Following Peripheral Nerve Injury

The maladaptive response of the central nervous system (CNS) following nerve injury is primarily linked to the activation of glial cells (reactive gliosis) that produce an inflammatory reaction and a wide cellular morpho-structural and functional/metabolic remodeling. Glial acidic fibrillary protein (GFAP), a major protein constituent of astrocyte intermediate filaments (IFs), is the hallmark of the reactive astrocytes, has pleiotropic functions and is significantly upregulated in the spinal cord after nerve injury. Here, we investigated the specific role of GFAP in glial reaction and maladaptive spinal cord plasticity following sciatic nerve spared nerve injury (SNI) in GFAP KO and wild-type (WT) animals. We evaluated the neuropathic behavior (thermal hyperalgesia, allodynia) and the expression of glial (vimentin, Iba1) and glutamate/GABA system markers (GLAST, GLT1, EAAC1, vGLUT, vGAT, GAD) in lumbar spinal cord sections of KO/WT animals. SNI induced neuropathic behavior in both GFAP KO and WT mice, paralleled by intense microglial reaction (Iba1 expression more pronounced in KO mice), reactive astrocytosis (vimentin increase) and expression remodeling of glial/neuronal glutamate/GABA transporters. In conclusion, it is conceivable that the lack of GFAP could be detrimental to the CNS as it lacks a critical sensor for neuroinflammation and morpho-functional-metabolic rewiring after nerve injury. Understanding the maladaptive morpho-functional changes of glial cells could represent the first step for a new glial-based targeted approach for mechanisms of disease in the CNS

Atividade antibacteriana e antifúngica de extratos etanólicos de Aster lanceolatus Willd., Asteraceae.

Conhecida popularmente como áster-arbustiva, margarida-de-são-miguel e monte-cassino, Aster lanceolatus é uma planta ornamental de corte. Sabendo-se que não existem estudos que atestem a atividade biológica desta espécie, procurou-se neste trabalho atividades antibacteriana e antifúngica. Para tanto se utilizaram extratos brutos etanólicos de duas porções distintas, das flores e dos caules com folhas. Para a atividade antibacteriana, oito bactérias patogênicas foram submetidas a ensaio de difusão em gel e concentração inibitória mínima. Demonstrou-se atividade do extrato bruto etanólico de flores contra Streptococcus pyogenes, em difusão em gel e atividade de extrato bruto etanólico de caules e folhas contra Salmonella typhimurium e Streptococcus pyogenes em concentração inibitória mínima. Para a atividade antifúngica, utilizaram-se três fungos patogênicos em ensaios de crescimento micelial em placas e bioautografia direta. No ensaio de crescimento micelial em placas verificou-se a inibição de Fusarium oxysporum e na bioautografia direta, inibição do Cylindrocladium spathulatum. Os resultados delinearam uma nova fonte de pesquisa, as plantas ornamentais. Estas podem ser fonte de constituintes químicos capazes de servirem como protótipos para novos agentes terapêuticos e para tratamento sanitário de plantas medicinais

Monitoring of blood serum amyloid (SAA) to predict outcome of first-line pembrolizumab (P) in patients (pts) with advanced non-small cell lung cancer (ANSCLC).

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Ozone tertiary treatment for pharmaceuticals and personal care products removal from municipal wastewater

An ozone pilot plant was installed at a conventional WWTP to evaluate the removal rate of emerging contaminants, drugs, and fragrances, as tertiary treatment. The filtered secondary effluent flow rate ranged between 1.3÷1.9 m3/h with a retention time of 10÷30 minutes and the plant operated with an ozone dose of 2- 4 mgO3/l. The results evidenced a high removal rate of 80-100% for most of the organic targeted compounds: Amisulpride, Azithromycin, Carbamazepine, Diclofenac, Clarithromycin and Ofloxacin. Lower removal rates from 20% to 80%, were observed for some substances e.g. Gabapentin Lactam, Galaxolidone, Irbesartan, Lamotrigine, and Tonalide. Advanced Oxidation Process (AOP) treatment with O3/H2O2, (0.5–1.0–2 molH2O2/molO3) allowed improved results for almost all these latter. In addition, ozone determined up to 42% removal of the absorbance at 254 nm and 20% of COD, wastewater disinfection, a decrease of the GC-MS chromatographic area, and no acute toxicity effect nor estrogenic and mutagen effects have been detected

The search of higher multipole radiation in gravitational waves from compact binary coalescences by a minimally-modelled pipeline

The coherent WaveBurst (cWB) pipeline implements a minimally-modelled search to find a coherent response in the network of gravitational wave detectors of the LIGO-Virgo Col-laboration in the time-frequency domain. In this manuscript, we provide a timely introduction to an extension of the cWB analysis to detect spectral features beyond the main quadrupolar emission of gravitational waves during the inspiral phase of compact binary coalescences; more detailed discussion will be provided in a forthcoming paper [1]. The search is performed by defining specific regions in the time-frequency map to extract the energy of harmonics of main quadrupole mode in the inspiral phase. This method has already been used in the GW190814 discovery paper (Astrophys. J. Lett. 896 L44). Here we show the procedure to detect the (3, 3) multipole in GW190814 within the cWB framework

Prospective Study of Loss of Health-Related Quality Adjusted Life Years in Children and their Families due to Uncomplicated and Hospitalised Varicella

Introduction and aims: Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. Methods: Children with varicella in the community and admitted to hospitals in Portugal were included over 18 months from January 2019. Children's and carers' HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. Results: Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0 days (95 % CI 1.9-2.2, n = 101) (mean 5.4 QALYs/1000 children (95 % CI 5.3-6.1) and 1.3 days/primary carer (95 % CI 1.2-1.6, n = 103) (mean 3.6 QALYs /1000 carers (95 % CI 3.4-4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8 days (95 % CI 9.4-10.6, n = 114) (mean 26.8 QALYs /1000 children (95 % CI 25.8-29.0) and 8.5 days/primary carer (95 % CI 7.4-9.6, n = 114) (mean 23.4 QALYs/1000 carers (95 % CI 20.3-26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95 % CI 43.9-97.6)]. Estimates for children's QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. Conclusions: The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.info:eu-repo/semantics/publishedVersio