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Immunotherapy and Gene Therapy for Oncoviruses Infections: A Review
No full textImmunotherapy has been shown to be highly effective in some types of cancer caused
by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to correct for
inappropriate gene products that cause/may cause diseases. Both these types of therapy have been
used as alternative ways to avoid cancers caused by oncoviruses. In this review, we summarize
recent studies on immunotherapy and gene therapy including the topics of oncolytic immunotherapy,
immune checkpoint inhibitors, gene replacement, antisense oligonucleotides, RNA interference,
clustered regularly interspaced short palindromic repeats Clustered Regularly Interspaced Short
Palindromic Repeats (CRISPR)-based gene editing, transcription activator-like effector nucleases
(TALENs) and custom treatment for Epstein–Barr virus, human T-lymphotropic virus 1, hepatitis
B virus, human papillomavirus, hepatitis C virus, herpesvirus associated with Kaposi’s sarcoma,
Merkel cell polyomavirus, and cytomegalovirus
The variants question: What is the problem?
No full textThe severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole‐genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS‐CoV‐2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called “variants of concerns” (VOCs), and/or “variants of interests” (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS‐CoV‐2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS‐CoV‐2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS‐CoV‐2 threat to better undersunderstand the virus genetic diversity and its potential impact on vaccination strategy
COVID-19 hospital admissions: Brazil's first and second waves compared
No full textSince January 2020 Elsevier has created a COVID-19 resource centre with
free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.Brazil is one of the countries most
affected by the COVID-19 pandemic,
with more than 16 million confirmed
cases and 454 429 confirmed
deaths by May 26, 2021 (according
to the Johns Hopkins Coronavirus
Resource Center). The beginning of
2021 was marked by a second wave
of COVID-19, which had different
features to the first wave,
with
simultaneous, explosive surges of
COVID-19 cases across different
regions of the country that added
enormous pressure to a health system
already under strain after a year of
the pandemic. This second wave was
contemporary with the discovery,
expansion, and dominance of variants
of interest (VoI) and variants of
concern (VoC) in Brazil
Informativo Nr. 162
No full textBoletim informativo desenvolvido pelo Nethis/Fiocruz Brasília com os principais eventos e notícias. Edição publicada no dia 24/12/2021
As portas abertas da história: a contribuição de Rita de Cássia para a história da saúde e das doenças no Brasil
No full textO presente trabalho configura-se como uma construção narrativa sobre a trajetória de vida e profissional da professora titular e pesquisadora Rita de Cássia Marques. Por meio da metodologia de história oral pública, entrevistamos Rita visando a construção de uma narrativa sobre a sua história de vida, levando em consideração o fazer do historiador no contexto da pandemia de Covid-19 e a constituição do próprio campo da História da Saúde e das Doenças no Brasil, campo em que atuou de forma pioneira no Brasil. Por meio da função social que a memória de Rita exerce sobre a construção do campo da História da Saúde e das Doenças e como essa experiência nos ajuda a pensar o tempo presente assolado pela pandemia e o fazer historiográfico por meio da temática do envelhecimento. Rita nos proporciona uma viagem no tempo, que atravessa os caminhos geracional, de gênero, raça, e personagens históricos de temporalidades distintas
CCL2 and IFN-γ serum levels as biomarkers for subclinical infection in household contacts of leprosy patients
No full textLeprosy, also known as Hansen\'s disease, is a long-term infection by the bacteria Mycobacterium leprae, and actually still persists as a serious public health problem. The clinical parameters are used for diagnosis, however, some studies have indicated the selection of a set of biomarkers of subclinical infection, both serological and cellular, that allow the early diagnosis. Some cytokines and chemokines have been differentially expressed in index cases (paucibacillary and multibacillary patients) and household contacts (HHC), and may present a potential biomarker of M. leprae subclinical infection. Thus, the aim of this study was to analyze the variations in the profile of cytokines and chemokines, longitudinally, between index cases and their household contacts with a view to identifying possible biomarkers with differential expression, which may guide the early subclinical infection in household contacts. A longitudinal study was carried out between 2014 and 2015. The serum levels of the cytokines and chemokines were measured in all patient samples by CBA (Cytometric Bead Array). We observed a reduction of IL-4 and IL-17 expression of HHC group in the second evaluation (T1), as also a reduction of IL-17 in MB. We observed increased expression of IL-2 in PB patients as well. HHC, PB and MB showed a similar reduction profile of the chemokines CXCL8, CXCL9 and CXCL10 from T0 to T1. Interestingly, only serological levels of CCL2 are increased after a follow-up of HHC group, and this group, but not PB and MB patients, showed a significant association and a negative correlation between CCL2 and IFN-gamma. The present study showed for the first time a similarity in the immunological scenario between HHC, PB and MB patients. In addition, this work highlights CCL2 chemokine in association with IFN-gamma as possible biomarkers of subclinical infection of HHC, as also a parameter of early infection monitoring
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors
No full textAbstract: Since exacerbated inflammation and microvascular leakage are hallmarks of dengue virus
(DENV) infection, here we interrogated whether systemic activation of the contact/kallikrein-kinin
system (KKS) might hamper endothelial function. In vitro assays showed that dextran sulfate, a
potent contact activator, failed to generate appreciable levels of activated plasma kallikrein (PKa)
in the large majority of samples from a dengue cohort (n = 70), irrespective of severity of clinical
symptoms. Impaired formation of PKa in dengue-plasmas correlated with the presence of cleaved
Factor XII and high molecular weight kininogen (HK), suggesting that the prothrombogenic contact
system is frequently triggered during the course of infection. Using two pathogenic arboviruses,
DENV or Zika virus (ZIKV), we then asked whether exogenous BK could influence the outcome
of infection of human brain microvascular endothelial cells (HBMECs). Unlike the unresponsive
phenotype of Zika-infected HBMECs, we found that BK, acting via B2R, vigorously stimulated
DENV-2 replication by reverting nitric oxide-driven apoptosis of endothelial cells. Using the mouse
model of cerebral dengue infection, we next demonstrated that B2R targeting by icatibant decreased
viral load in brain tissues. In summary, our study suggests that contact/KKS activation followed
by BK-induced enhancement of DENV replication in the endothelium may underlie microvascular
pathology in dengue
DiagnoTop: A computational pipeline for discriminating bacterial pathogens without database search
No full textPathogen identification is crucial to confirm bacterial infections and guide antimicrobial therapy. Although
MALDI-TOF mass spectrometry (MS) serves as foundation for tools that enable rapid microbial identification, some bacteria remain challenging to identify. We recently showed that top-down proteomics (TDP) could be used to discriminate closely related enterobacterial pathogens (Escherichia coli, Shigella, and Salmonella)
that are indistinguishable with tools rooted in the MALDI-TOF MS approach. Current TDP diagnostic relies on the identification of specific proteoforms for each species through a database search. However, microbial proteomes are often poorly annotated, which complicates the large-scale identification of proteoforms and leads to many unidentified high-quality mass spectra. Here, we describe a new computational pipeline called DiagnoTop that lists discriminative spectral clusters found in TDP data sets that can be used for microbial diagnostics without database search. Applied to our enterobacterial TDP data sets, DiagnoTop could easily shortlist highquality discriminative spectral clusters, leading to increased diagnostic power. This pipeline opens new perspectives in clinical microbiology and biomarker discovery using TDP
Predictors of sarcopenia in young hospitalized patients living with HIV
No full textThe prevalence of sarcopenia in hospitalized people living with HIV is underdiagnosed, as assessment instruments are not always available. This study aimed to identify factors related to sarcopenia, correlating their anthropometric and clinical markers in hospitalized people living with HIV. This was an observational cross-sectional clinical study, carried out from September 2018 through October 2019. Handgrip strength, muscle mass index, calf circumference and gait speed test were evaluated in recruited patients within three days of hospital admission. The sample consisted in 44 patients, mostly men (66%), black (68%), young adults (41.65±12.18 years) and immunodeficient (CD4 cell count 165 cells/mm3 [34.25-295.5]). Sarcopenia was present in 25% of the sample. Calf circumference showed a significant correlation with CD4 cell count and viral load (p31cm and gait speed test>0.8m/s reduced the chance of sarcopenia by 60% (OR=0.396 [-1.67 to -0.18]; p31cm and gait speed test>0.8m/s are associated with a reduced chance of sarcopenia in hospitalized HIV patients
Intracerebral hemorrhage associated with vaccine-induced thrombotic thrombocytopenia following ChAdOx1 nCOVID-19 vaccine in a pregnant woman
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