Herpes Simplex Virus Type 1 Infection of the Central Nervous System: Insights Into Proposed Interrelationships With Neurodegenerative Disorders

Herpes simplex virus type 1 (HSV-1) is highly prevalent in humans and can reach the brain without evident clinical symptoms. Once in the central nervous system (CNS), the virus can either reside in a quiescent latent state in this tissue, or eventually actively lead to severe acute necrotizing encephalitis, which is characterized by exacerbated neuroinflammation and prolonged neuroimmune activation producing a life-threatening disease. Although HSV-1 encephalitis can be treated with antivirals that limit virus replication, neurological sequelae are common and the virus will nevertheless remain for life in the neural tissue. Importantly, there is accumulating evidence that suggests that HSV-1 infection of the brain both, in symptomatic and asymptomatic individuals could lead to neuronal damage and eventually, neurodegenerative disorders. Here, we review and discuss acute and chronic infection of particular brain regions by HSV-1 and how this may affect neuron and cognitive functions in the host. We review potential cellular and molecular mechanisms leading to neurodegeneration, such as protein aggregation, dysregulation of autophagy, oxidative cell damage and apoptosis, among others. Furthermore, we discuss the impact of HSV-1 infection on brain inflammation and its potential relationship with neurodegenerative diseases

Life Cycle Inventory for artisanal production of Macauba liquor in the territory of Serro / Minas Gerais

A Macaúba (Acrocomia aculeata) é uma palmeira perene, com ampla produtividade. Presente em diferentes ecossistemas brasileiros, é encontrada na Região do Serro, Minas Gerais, como uma árvore nativa. Diante das diversas possibilidades de aproveitamento do fruto, o objetivo deste artigo é analisar os impactos ambientais advindos da produção do licor de macaúba, no território do Serro-MG, por meio da metodologia de Avaliação do Ciclo de Vida. O inventário realizado identificou um ciclo de vida que inclui 12 processos, desde o crescimento da fruta, até o consumo do licor. Por se tratar de uma bebida, cujo final do ciclo de vida gera resíduos passíveis de reuso e reciclagem, o principal impacto identificado refere-se às emissões de CO2 , advindas dos transportes necessários nos processos. Ainda assim, deve ser considerado o sequestro de carbono, realizado pelas próprias palmeiras de macaúba, durante seu crescimento.Macauba (Acrocomia aculeata) is a perennial palm tree, which has ample productivity. Present in different Brazilian ecosystems, it is found in the Serro Region, Minas Gerais, Brazil, as a native tree. Given the various possibilities of using the fruit, the objective of this paper is to analyse the environmental impacts arising from the production of macauba liquor, in the Serro-MG territory, through the Life Cycle Assessment methodology. The inventory carried out identified a life cycle that includes 12 processes, from the growth of the fruit to the consumption of the liquor. As it is a drink, the end of the life cycle of which generates waste that can be reused and recycled, the main impact identified refers to CO2 emissions, resulting from the necessary transport in the processes. Even so, carbon sequestration, carried out by the macauba palms themselves, during their growth must be considered

Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro

Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) produce lifelong infections and are highly prevalent in the human population. Both viruses elicit numerous clinical manifestations and produce mild-to-severe diseases that affect the skin, eyes, and brain, among others. Despite the existence of numerous antivirals against HSV, such as acyclovir and acyclovir-related analogs, virus variants that are resistant to these compounds can be isolated from immunosuppressed individuals. For such isolates, second-line drugs can be used, yet they frequently produce adverse side effects. Furthermore, topical antivirals for treating cutaneous HSV infections usually display poor to moderate efficacy. Hence, better or novel anti-HSV antivirals are needed and details on their mechanisms of action would be insightful for improving their efficacy and identifying specific molecular targets. Here, we review and dissect the lytic replication cycles of herpes simplex viruses, discussing key steps involved in cell infection and the processes that yield new virions. Additionally, we review and discuss rapid, easy-to-perform and simple experimental approaches for studying key steps involved in HSV replication to facilitate the identification of the mechanisms of action of anti-HSV compounds

Contribution of viral and bacterial infections to senescence and immunosenescence

Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated β-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host’s susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review

Desenvolvimento de processos de pré-tratamento da biomassa para a separação eficiente das correntes de lenhina e de açúcares

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMO: O fracionamento da biomassa é um dos principais pontos críticos no desenvolvimento das biorrefinarias. Neste trabalho, são apresentadas três estratégias inovadoras com vista à separação seletiva das frações de celulose, hemicelulose e lenhina, utilizando compostos orgânicos, geralmente em solução aquosa: i) utilização de líquidos iónicos (ILs) em particular [emim][OAc] e [emim][HSO4]); ii) processos organosolv baseados na utilização de misturas etanol:água (50:50); e iii) um processo não aquoso baseado em imidazole. Os processos com ILs permitiram um fracionamento diferencial e, em geral, uma redução da cristalinidade da celulose. Os processos organosolv permitiram modular a distribuição de produtos derivados da hemicelulose e da lenhina entre as fases sólida e líquida. A utilização de imidazole, permitiu a separação das duas frações de polissacáridos e contribuiu para despolimerização da lenhina.ABSTRACT: The biomass fractionation is one of the main critical points in the technological development of biorefineries. In this work, three innovative fractionation strategies aiming the selective separation of the cellulose, hemicellulose and lignin fractions, using organic compounds, generally in aqueous solution, are presented and discussed: i) use of ionic liquids (ILs), in particular [emim][OAc ] and [emim][HSO4]); ii) organosolv process based on ethanol:water mixture (50:50); and iii) a non-aqueous process based on imidazole. The processes with ILs allowed a differential fractionation and, in general a decrease of cellulose crystallinity. The organosolv process enabled the modulation of the distribution of hemicellulose and lignin-derived products between the solid phase and the liquid phase. The use of imidazole, allowed the separation of the two polysaccharide fractions and contributed to lignin depolymerization, producing phenolic compounds whose molecular weight is a function of severity.info:eu-repo/semantics/publishedVersio

Evaluación de las conductas de salud en jóvenes universitarios

Objetivo Construir y analizar las propiedades psicométricas de un cuestionario que evalúa las conductas de salud que hacen parte del estilo de vida de los universitarios. Métodos Se realizó un estudio de validación con dos fases. La primera con 1485 estudiantes (63,2 % mujeres), de cuatro universidades de Colombia, cuya edad media fue de 20,7 años (DT= 2,5). La segunda con 1811 estudiantes (55,8 % mujeres) de seis universidades del país, con una edad media de 19,7 (DT= 2,0). Se hicieron análisis para la validez de contenido, análisis de discriminación de ítems, análisis factoriales y de consistencia interna. Resultados La versión final del “Cuestionario de estilos de vida de jóvenes universitarios” [CEVJU-R] quedó constituida por 40 ítems que evalúan conductas en ocho dimensiones del estilo de vida: Actividad física, Tiempo de ocio, Alimentación, Consumo de alcohol, cigarrillo y drogas ilegales, Sueño, Habilidades interpersonales, Afrontamiento y Estado emocional percibido. Adicionalmente, incluyó 28 ítems que evalúan, en siete de las ocho dimensiones, las motivaciones para llevar a cabo o no las prácticas y para cambiarlas, así como los recursos que facilitan o dificultan su realización. El nivel de fiabilidad de las dimensiones fue de aceptable a moderado (entre 0,6 y 0,7). Conclusiones El CEVJU-R presenta propiedades psicométricas adecuadas y constituye un avance en la medición de los estilos de vida de los universitarios. Podría utilizarse para la identificación de las necesidades de los jóvenes y para la definición de las acciones de promoción y prevención dentro de las universidades

Factors related to the development of high antibody titres against SARS-CoV-2 in convalescent plasma donors from the ConPlas-19 trial

Background and objectives: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels. Materials and methods: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA. Results: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06). Conclusion: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.European Regional Development Fund (FEDER); Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, Grant/Award Number: COV20/00072; SCReN (Spanish Clinical Research Network), Instituto de Salud Carlos III, Grant/Award Number: PT17/0017/0009S

Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope

Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive diagnostic workup and even more for new, effective antifungal drugs to improve patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp. and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScopeVR registry. For 208 Scedosporium spp. infections solid organ transplantation (n¼58, 27.9%) and for 56 L. prolificans infection underlying malignancy (n¼28, 50.0%) were the most prevalent risk factors. L. prolificans infections frequently presented as fungemia (n¼26, 46.4% versus n¼12, 5.8% for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better overall outcome in both groups compared to treatment with amphotericin B formulations. This review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificansWe thank Sabine Wrackmeyer for her private donation to support the projec

Whole-genome sequencing resolves a polyclonal outbreak by extended-spectrum beta-lactam and carbapenem-resistant Klebsiella pneumoniae in a Portuguese tertiary-care hospital.

Klebsiella pneumoniae has emerged as an important nosocomial pathogen, with whole-genome sequencing (WGS) significantly improving our ability to characterize associated outbreaks. Our study sought to perform a genome-wide analysis of multiclonal K. pneumoniae isolates (n=39; 23 patients) producing extended spectrum beta-lactamases and/or carbapenemases sourced between 2011 and 2016 in a Portuguese tertiary-care hospital. All isolates showed resistance to third-generation cephalosporins and six isolates (five patients) were also carbapenem resistant. Genome-wide-based phylogenetic analysis revealed a topology representing ongoing dissemination of three main sequence-type (ST) clades (ST15, ST147 and ST307) and transmission across different wards, compatible with missing links that can take the form of undetected colonized patients. Two carbapenemase-coding genes were detected: blaKPC-3, located on a Tn4401d transposon, and blaGES-5 on a novel class 3 integron. Additionally, four genes coding for ESBLs (blaBEL-1, blaCTX-M-8, blaCTX-M-15 and blaCTX-M-32) were also detected. ESBL horizontal dissemination across five clades is highlighted by the similar genetic environments of blaCTX-M-15 gene upstream of ISEcp1 on a Tn3-like transposon. Overall, this study provides a high-resolution genome-wide perspective on the epidemiology of ESBL and carbapenemase-producing K. pneumoniae in a healthcare setting while contributing for the adoption of appropriate intervention and prevention strategies

Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial

BACKGROUND: The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. METHODS: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac® separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. RESULTS: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-g and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-g secretion. CONCLUSIONS: Immunization with CoronaVac® in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. FUNDING: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. CLINICAL TRIAL NUMBER: NCT04651790