Selective Disruption of the Blood–Brain Barrier by Zika Virus

The blood–brain barrier (BBB) selectively regulates the cellular exchange of macromolecules between the circulation and the central nervous system (CNS). Here, we hypothesize that Zika virus (ZIKV) infects the brain via a disrupted BBB and altered expression of tight junction (TJ) proteins, which are structural components of the BBB. To assess this hypothesis, in vitro and in vivo studies were performed using three different strains of ZIKV: Honduras (ZIKV-H), Puerto Rico (ZIKV-PR), and Uganda (ZIKV-U). Primary human brain microvascular endothelial cells (BMECs) were productively infected by all studied ZIKV strains at MOI 0.01, and were analyzed by plaque assay, immunofluorescence for NS1 protein, and qRT-PCR at 2 and 6 days post-infection (dpi). Compared to mock-infected controls, expression level of ZO-1 was significantly upregulated in ZIKV-H-infected BMECs, while occludin and claudin-5 levels were significantly downregulated in BMECs infected by all three studied viral strains. Interestingly, BMEC permeability was not disturbed by ZIKV infection, even in the presence of a very high viral load (MOI 10). All studied ZIKV strains productively infected wild-type C57BL/J mice after intravenous infection with 107 PFU. Viral load was detected in the plasma, spleen, and brain from 1 to 8 dpi. Peak brain infection was observed at 2 dpi; therefore, TJ protein expression was assessed at this time point. Claudin-5 was significantly downregulated in ZIKV-U-infected animals and the BBB integrity was significantly disturbed in ZIKV-H-infected animals. Our results suggest that ZIKV penetrates the brain parenchyma early after infection with concurrent alterations of TJ protein expression and disruption of the BBB permeability in a strain-dependent manner

A equipe da Unidade de Terapia Intensiva frente ao cuidado paliativo: discurso do sujeito coletivo

OBJETIVO Conhecer a percepção dos profissionais de saúde de uma Unidade de Terapia Intensiva acerca do cuidado paliativo. MÉTODO Pesquisa descritiva, qualitativa do tipo Convergente Assistencial realizada em uma Unidade de Terapia Intensiva da região sul do Brasil. Utilizou-se de entrevista semiestruturada que investigou o entendimento e a compreensão sobre cuidado paliativo nesta unidade. Os dados foram organizados e analisados pela técnica do discurso do sujeito coletivo com auxílio do software Qualiquantisoft®. RESULTADOS Participaram do estudo 37 profissionais (12 enfermeiros, 11 técnicos de enfermagem, cinco fisioterapeutas e nove médicos). As ideias centrais extraídas dos relatos: cuidado na fase terminal da vida sem medidas fúteis; cuidados de conforto; falta uniformizar a assistência e falta capacitação para a equipe. CONCLUSÃO Os profissionais percebem o cuidado paliativo apropriado na fase terminal da vida, sem necessidade de medidas fúteis de tratamento e promotoras de conforto. No entanto, estão conscientes da falta de uniformização e da sua capacitação nesta matéria, o que os leva a conceber o paliativismo como cuidado de terminalidade, pelo que se recomendam medidas para romper com este estigma.OBJETIVO Conocer la percepción de los profesionales sanitarios de una Unidad de Cuidados Intensivos acerca del cuidado paliativo. MÉTODO Investigación descriptiva, cualitativa del tipo Convergente Asistencial realizada en una Unidad de Cuidados Intensivos de la región sur de Brasil. Se empleó entrevista semiestructurada que investigó el entendimiento y la comprensión acerca del cuidado paliativo en esa unidad. Los datos fueron organizados y analizados por la técnica del discurso del sujeto colectivo con auxilio del software Qualiquantisoft®. RESULTADOS Participaron en el estudio 37 profesionales (12 enfermeros, 11 técnicos de enfermería, cinco fisioterapeutas y nueve médicos). Las ideas centrales extraídas de los relatos: cuidado en la fase terminal de la vida sin medidas fútiles; cuidados de confort; ausencia de uniformización de la asistencia y de capacitación para el equipo. CONCLUSIÓN Los profesionales perciben el cuidado paliativo apropiado en la fase terminal de la vida, sin necesidad de medidas fútiles de tratamiento y promotoras de confort. Sin embargo, están enterados de la falta de uniformización y de su capacitación en esa materia, lo que lleva a concebir el paliativismo como cuidado de terminalidad, por lo que se recomiendan medidas para romper dicho estigma.OBJECTIVE To learn the perception of health professionals in an intensive care unit towards palliative care. METHOD This was a descriptive and qualitative study based on the converging care approach conducted at an intensive care unit in the South of Brazil. Semi-structured interviews were used to investigate the understanding of the professionals about palliative care in this unit. The data were organized and analyzed using the discourse of the collective subject method with the help of Qualiquantisoft® software. RESULTS Participants included 37 professionals (12 nurses, 11nursing technicians, 5 physical therapists and 9 doctors). The key ideas extracted from the interviews were: care in the end stage of life that avoids futile measures; comfort care; lack of standardized care and lack of team training. CONCLUSION The professionals perceived palliative care as appropriate in the last stages of life, with no need for futile treatment or as comfort measures. However, they are aware of the lack of standardization and lack of capacity building in this area, which leads them to conceive palliative care as terminal care, and measures are recommended to break with this stigma

Fatores preditores de óbito em Unidade de Terapia Intensiva: contribuição para a abordagem paliativista

Objetivo Factores predictivos de defunción en la Unidad de Cuidados Intensivos y relacionar a pacientes elegibles para cuidados paliativos preferentes. Método Cohorte prospectivo que evaluó a pacientes hospitalizados por más de 24 horas, subdivididos en G1 (pacientes que fallecieron) y G2 (pacientes con alta hospitalaria). Para la identificación de los factores predictivos para el resultado defunción, se hizo al médico intensivista la “pregunta sorpresa” y fueron recogidos datos clínico-demográficos de los pacientes. Los datos fueron analizados por estadística descriptiva/inferencial (significante pObjetivo Identificar preditores de óbito na Unidade de Terapia Intensiva e relacionar pacientes elegíveis para cuidados paliativos preferenciais. Método Coorte prospectivo que avaliou pacientes internados por mais de 24 horas, subdivididos em G1 (pacientes que morreram) e G2 (pacientes com alta hospitalar). Para a identificação dos fatores preditores para o desfecho óbito, foi feita ao médico intensivista a “pergunta-surpresa” e foram coletados dados clínico-demográficos dos pacientes. Os dados foram analisados por estatística descritiva/inferencial (significante pObjective To identify predictors of death in the Intensive Care Unit and relate eligible patients to preferential palliative care. Method A prospective cohort study that evaluated patients hospitalized for more than 24 hours, subdivided into G1 (patients who died) and G2 (patients who were discharged from hospital). For identifying the predictors for death outcome, the intensivist physician was asked the “surprise question” and clinical-demographic data were collected from the patients. Data were analyzed by descriptive/inferential statistics (

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe