Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe ...acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.
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•Spike protein infusion into mouse brain induces late cognitive dysfunction•Spike protein induces late hippocampal microgliosis and synapse loss•Blockage of TLR4 renders mice resistant to Spike-induced cognitive dysfunction•TLR4-2604G>A GG genotype was related to poor cognitive outcome in COVID-19 patients
Cognitive impairment is frequent in post-COVID-19 syndrome patients, but its underlying mechanisms are unclear. Fontes-Dantas et al. show that Spike brain infusion in mice induces late neuroinflammation and synapse loss, leading to long-term cognitive impairment mediated by TLR4 signaling. In patients, genotype GG TLR4-2604G>A was associated with poor cognitive outcome.
Limb‐girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical ...and molecular data of patients with autosomal recessive LGMD2/LGMD‐R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD‐R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD‐R1‐calpain3‐related, LGMD2B/LGMD‐R2‐dysferlin‐related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD‐R, most frequent subtypes were LGMD2A/LGMD‐R1‐calpain3‐related and LGMD2B/LGMD‐R2‐dysferlin‐related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood‐onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD‐R7‐telethonin‐related, an ultra‐rare subtype worldwide. Females with LGMD2B/LGMD‐R2‐dysferlin‐related had less severe progression to handicap than males and LGMD2A/LGMD‐R1‐calpain3‐related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD‐R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.
Linn bark is used to treat dysentery by various populations in Southeast Asian countries, and its leaves have also been used in traditional medicine to treat hepatitis in India and the Philippines. ...Here, the antifungal actions of crude hydro-alcoholic extract (TcHE) and fractions from
leaves were assessed via the agar diffusion and microdilution tests on
reference strains and clinical isolates from patients with acquired immunodeficiency syndrome (AIDS). Additionally, the potential cytotoxic effects of TcHE were assessed on cultured human peripheral blood mononuclear cells (PBMC).
fractions and sub-fractions were analyzed by gas chromatography coupled to mass spectrometry with electron impact (GC/MS/EI), high-performance liquid chromatography coupled to mass spectrometry "electrospray" ionization in positive mode (HPLC/MS/MS/ESI
) and hydrogen nuclear magnetic resonance (
HNMR). TcHE and its fractions were able to inhibit the growth of all tested
strains with the
-butanol (FBuOH) fraction presenting the best antifungal activity. Testing of different FBuOH sub-fractions (SF) showed that SF10 was the most active against
spp. Fractioning of SF10 demonstrated that 5 out of its 15 sub-fractions were active against
spp., with SF10.5 presenting the highest activity. Chemical analysis of SF10 detected hydrolysable tannins (punicalin, punicalagin), gallic acid and flavonoid C-glycosides. Overall, the results showed that
L. leaf extract, fractions and sub-fractions were antifungal against
spp. and may be useful to treat diseases caused by this fungus.
Hepatitis C virus(HCV) infection is highly prevalent among chronic kidney disease(CKD) subjects under hemodialysis and in kidney transplantation(KT) recipients, being an important cause of morbidity ...and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on managementand treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon(PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus.
•Post-septic mice are more susceptible to synapse and cognitive damage induced by AβO.•Sepsis induces long-lasting innate imune memory in the brain.•AβO induces microglial phagocytosis of hippocampal ...synaptic terminals in pos-septic mice.
Sepsis survivors show long-term impairments, including alterations in memory and executive function. Evidence suggests that systemic inflammation contributes to the progression of Alzheimeŕs disease (AD), but the mechanisms involved in this process are still unclear. Boosted (trained) and diminished (tolerant) innate immune memory has been described in peripheral immune cells after sepsis. However, the occurrence of long-term innate immune memory in the post-septic brain is fully unexplored. Here, we demonstrate that sepsis causes long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to Aβ oligomers (AβO), central neurotoxins found in AD. Hippocampal microglia from sepsis-surviving mice shift to an amoeboid/phagocytic morphological profile when exposed to low amounts of AβO, and this event was accompanied by the upregulation of several pro-inflammatory proteins (IL-1β, IL-6, INF-γ and P2X7 receptor) in the mouse hippocampus, suggesting that a trained innate immune memory occurs in the brain after sepsis. Brain exposure to low amounts of AβO increased microglial phagocytic ability against hippocampal synapses. Pharmacological blockage of brain phagocytic cells or microglial depletion, using minocycline and colony stimulating factor 1 receptor inhibitor (PLX3397), respectively, prevents cognitive dysfunction induced by AβO in sepsis-surviving mice. Altogether, our findings suggest that sepsis induces a long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to AβO-induced neurotoxicity and cognitive impairment.
Fault detection in computer networks is a difficult task, since most faults, attacks or abnormalities may not be observed in advance and modeled prior to the event. In addition, network attacks tend ...to disguise broken rules by minimizing their resemblance to previous trials, which makes it even more difficult to use past observed data to obtain detection models. High dimensionality in relation to the number of network elements and observable variables is also a major concern. Instead of modeling the fault itself, the work presented in this paper describes a detection model that is based on detecting drifts from normality. This problem is treated in the present paper by weekly updating the estimation of density functions that represent normality or as close as possible to this rate. Abnormalities are detected by thresholding drifts from the estimated densities. Root cause analysis can also be accomplished by tracing back combined variables output from principal component analysis projections. The method is scalable for large networks and was tested on real data from a large company with the developed online monitoring platform.
► Adding value to marine macro-algae Laminaria digitata. ► Separation and recovery of trivalent chromium ions. ► FTIR analysis revealed a complex nature of the biomass. ► Carboxyl and sulfonic groups ...where responsible for chromium binding.
In this study, Laminaria seaweed was used in its protonated form as an effective biosorbent for chromium(III) removal from aqueous solutions. The effect of different operating conditions (pH, initial metal concentration and temperature) on the efficiency of the biosorption process was assessed. Biosorption was strongly dependent on the solution pH and less dependent on the temperature. The Cr(III) adsorption capacity of the seaweed increased with the pH. The maximum uptake capacity for Cr(III) was 42mgg−1 at pH 4, considering a maximum initial chromium concentration of 250mgg−1, at 25°C. Langmuir and Freundlich models were able to fit well the experimental equilibrium data. The Langmuir equilibrium model parameters at pH=4 and T=25°C are qmax=41±1mgg−1 and KL=0.31±0.04Lmg−1. The adsorptive behavior of biosorbent particles was modeled using a batch reactor mass transfer kinetic model, which successfully predicts Cr(III) concentration profiles, with an average homogeneous diffusivity, Dh, of 0.13×10−8±0.08cm2s−1. The biosorbent was characterized in terms of apparent density, real density, porosity, particle size and pore size distribution. The chemical characterization of the biosorbent was based on the determination of the main chemical constituents present in the structure of the biomass, and in the identification of active sites on the surface, by the Fourier Transform Infrared Spectroscopy (FTIR) technique. FTIR analysis of Laminaria digitata revealed the complex nature of the biomass, with different binding groups, such as carboxyl and sulfonic, which are responsible for the binding of the metals.
This work aims at developing a video-based surveillance system for safety purposes in nuclear plants. The objective is to assess the radiation dose received by nuclear plant personnel, while they ...execute daily tasks, by means of computer vision methods. The system is conceived to provide some redundancy to the radioprotection means currently in use, being independent and complementary to them. After evaluating some methods from the literature for automatic target detection and tracking, a novel system is developed to correctly detect, track and identify people, so that the radiation dose received by each person is reliably computed. The video data are supplied by cameras installed in the nuclear plant room. Radiation dose rate mapping is combined with the tracking results to account for the received doses. We provide experimental results from a research reactor room, which show that the proposed system achieves radiation dose estimates that are in general similar to the ones of the ground truth. The database developed in this work for performance evaluation has been made publicly available for the research community.
•A video-based surveillance system was developed to estimate the radiation doses received by nuclear plant personnel while they execute their tasks.•The system is based on markerless computer vision methods for detecting and tracking people in videos.•The system combines the tracked people's positions with radiation dose rate mapping within the nuclear plant to account for the doses received.•Good results were achieved, compared to the corresponding doses computed based on ground truth positions.•The system can improve safety for nuclear plant personnel, since it can supply results faster than TLD based ones, and more precisely than the ones based on ionization chambers (pen dosimeters), the latter approaches currently in use.
O manejo de dispositivos cardíacos eletrônicos implantáveis de pacientes que evoluem a óbito tem sido motivo de controvérsia. Em nosso meio, não há recomendações uniformes, estando baseadas ...exclusivamente em protocolos institucionais e em costumes regionais. Quando o cadáver é submetido para cremação, além de outros cuidados, recomenda-se a retirada do dispositivo devido ao risco de explosão e dano do equipamento crematório. Principalmente no contexto da pandemia causada pelo SARS-Cov-2, a orientação e organização de unidades hospitalares e serviços funerários é imprescindível para minimizar o fluxo de pessoas em contato com fluidos corporais de indivíduos falecidos por COVID-19. Nesse sentido, a Sociedade Brasileira de Arritmias Cardíacas elaborou este documento com orientações práticas, tendo como base publicações internacionais e recomendação emitida pelo Conselho Federal de Medicina do Brasil.
The management of cardiac implantable electronic devices after death has become a source of controversy. There are no uniform recommendations for such management in Brazil; practices rely exclusively ...on institutional protocols and regional custom. When the cadaver is sent for cremation, it is recommended to remove the device due to the risk of explosion and damage to crematorium equipment, in addition to other precautions. Especially in the context of the SARS-CoV-2 pandemic, proper guidance and organization of hospital mortuary facilities and funeral services is essential to minimize the flow of people in contact with bodily fluids from individuals who have died with COVID-19. In this context, the Brazilian Society of Cardiac Arrhythmias has prepared this document with practical guidelines, based on international publications and a recommendation issued by the Brazilian Federal Medical Council.
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