Publications by authors named "Filipe A da Silva"

Background: The coronavirus-related disease (COVID-19) is mainly characterized by a respiratory involvement. The renin-angiotensin system (RAS) has a relevant role in the pathogenesis of COVID-19, as the virus enters host's cells via the angiotensin-converting enzyme 2 (ACE2).

Methods: This investigator-initiated, seamless phase 1-2 randomized clinical trial was conceived to test the safety and efficacy of continuous short-term (up to 7 days) intravenous administration of Angiotensin-(1-7) in COVID-19 patients admitted to two intensive care units (ICU).

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.

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Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR.

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Uncontrolled vasodilation is known to account for hypotension in the advanced stages of sepsis and other systemic inflammatory conditions, but the mechanisms of hypotension in earlier stages of such conditions are not clear. By monitoring hemodynamics with the highest temporal resolution in unanesthetized rats, in combination with ex-vivo assessment of vascular function, we found that early development of hypotension following injection of bacterial lipopolysaccharide is brought about by a fall in vascular resistance when arterioles are still fully responsive to vasoactive agents. This approach further uncovered that the early development of hypotension stabilized blood flow.

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Alamandine is a heptapeptide from the renin-angiotensin system (RAS) with similar structure/function to angiotensin-(1-7) [ang-(1-7)], but they act via different receptors. It remains elusive whether alamandine is an antiproliferative agent like ang-(1-7). The goal of this study was to evaluate the potential antiproliferative activity of alamandine and the underlying cellular signaling.

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Background And Purpose: Bradykinin (BK-(1-9)) is an endogenous nonapeptide involved in multiple physiological and pathological processes. Peptide fragments of bradykinin are believed to be biologically inactive. We have now tested the two major peptide fragments of bradykinin in human and animals.

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Article Synopsis
  • Recent SARS-CoV-2 variants have raised concerns about increased transmission within communities, prompting an investigation into their impact on hospital settings.
  • A study analyzed viral sequences and epidemiological data from patients in nine UK hospitals to assess the likelihood of healthcare-associated infections being caused by the Alpha variant versus community-acquired infections.
  • The results indicated no significant difference in the transmission of the Alpha variant compared to other lineages, suggesting existing infection control measures in UK hospitals are effective at containing the spread of emergent variants.
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  • Patients on haemodialysis are at a higher risk for severe illness from SARS-CoV-2, prompting a study in six Scottish dialysis units to understand infection transmission better.
  • Researchers used genomic sequencing data combined with geographical and temporal information to determine the sources of infection for patients in these units.
  • Out of 671 patients, 60 were infected, resulting in 16 deaths, and the study identified multiple transmission routes: within the unit, from the community, and from the hospital.
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We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L, which is located in the 5' UTR.

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  • * Researchers are studying a vampire bat betaherpesvirus (DrBHV) as a potential vaccine vector for rabies, finding that it infects 80-100% of bats at various sites in Peru, indicating strong potential for vaccine distribution.
  • * The study shows that DrBHV is specific to certain bat species, minimizing risks to other animals, and suggests that it could successfully compete with wild-type rabies viruses, making it a strong candidate for a new rabies vaccine strategy.
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The emergence and spread of tick-borne arboviruses pose an increased challenge to human and animal health. In Europe this is demonstrated by the increasingly wide distribution of tick-borne encephalitis virus (TBEV, Flavivirus, Flaviviridae), which has recently been found in the United Kingdom (UK). However, much less is known about other tick-borne flaviviruses (TBFV), such as the closely related louping ill virus (LIV), an animal pathogen which is endemic to the UK and Ireland, but which has been detected in other parts of Europe including Scandinavia and Russia.

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Article Synopsis
  • Virus emergence mechanisms are often unclear, making outbreaks unpredictable, as seen with the Bluetongue virus serotype 8 (BTV-8) outbreaks in Europe, which began in 2006 and re-emerged in 2015 despite prior control efforts.
  • Phylogenetic analysis of 164 BTV-8 genomes revealed minimal evolutionary change between the two outbreaks, suggesting that the virus did not replicate for several years during this period.
  • The researchers propose that the second outbreak may have been triggered by livestock exposure to frozen virus-contaminated materials from the earlier outbreak, underlining the need for improved disease surveillance in livestock and demonstrating the value of genomic studies in understanding infectious diseases.
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The Parati River contributes to the Babitonga Bay water complex, but the contents of the bay also influence the river during periods of inverted currents. In this study, the water quality along four stretches of the Parati River and Babitonga Bay was evaluated using chemical (physico-chemical and chromatographic analysis), microbiological (fluorescein diacetate hydrolysis) and ecotoxicological (Lumistox) methods to assess the reciprocal influence of the waters of this river-bay system. In addition, the most appropriate type of analysis for the monitoring of the estuarine region of the Parati River was identified.

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Objectives: Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool.

Methods: Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays.

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As antimicrobial signalling molecules, type III or lambda interferons (IFNλs) are critical for defence against infection by diverse pathogens, including bacteria, fungi and viruses. Counter-intuitively, expression of one member of the family, IFNλ4, is associated with decreased clearance of hepatitis C virus (HCV) in the human population; by contrast, a natural frameshift mutation that abrogates IFNλ4 production improves HCV clearance. To further understand how genetic variation between and within species affects IFNλ4 function, we screened a panel of all known extant coding variants of human IFNλ4 for their antiviral potential and identify three that substantially affect activity: P70S, L79F and K154E.

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Background: Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy.

Methods: To understand these clinical differences, we compared gene transcription profiles in liver biopsies from patients infected with either gt1 or gt3, and uninfected controls.

Results: Gt1-infected biopsies displayed elevated levels of transcripts regulated by type I and type III interferons (IFN), including genes that predict response to IFN-α therapy.

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