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1.
J Med Virol ; 96(5): e29621, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38654686

RESUMO

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.


Assuntos
Surtos de Doenças , Humanos , Brasil/epidemiologia , Masculino , Feminino , Adulto , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Animais , Zoonoses/epidemiologia , Zoonoses/virologia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Criança , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Anticorpos Antivirais/sangue , Idoso , Imunoglobulina G/sangue
2.
Viruses ; 15(7)2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37515231

RESUMO

COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account sex, vaccination, hospitalization, and age. Fatigue and myalgia were the most common symptoms, and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant to the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.


Assuntos
COVID-19 , Imunoglobulina A , Adulto , Idoso , Humanos , SARS-CoV-2 , Brasil/epidemiologia , Hospitalização , Anticorpos Antivirais , Imunoglobulina M
3.
Inorg Chem ; 62(27): 10635-10644, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37358196

RESUMO

Rare-earth manganese pyrochlores (R2Mn2O7) are frustrated magnetic materials, which previously have only been accessed using expensive high-pressure and high-temperature synthesis. In the present work, we demonstrate a convenient synthetic approach to synthesize R2Mn2O7 pyrochlores at ambient pressure. A series of pyrochlores (R = Y, Ho-Lu) were prepared by a simple and cost-effective molten salt method using NaCl and KCl as the flux. Moreover, phase-selectivity was demonstrated for yttrium manganese oxides (YMnO3 and Y2Mn2O7) by a simple variation of synthesis temperature and precursors-to-chlorides ratio. The synthetic procedure does not require high pressures or temperatures nor oxygen flow. All synthesized pyrochlores demonstrated ferromagnetic behavior at low temperature, and the magnetic properties were in good agreement with those of high-pressure-synthesized materials. The versatility of the method was confirmed by the preparation of a mixed-rare earth Y0.4Er0.4Tm0.4Yb0.4Lu0.4Mn2O7 solid solution─a compositionally complex high-entropy oxide.

5.
Microbiol Spectr ; 10(6): e0201222, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36448777

RESUMO

The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 103 PFU/mL (Alpha), 2.5 × 102 PFU/mL (Delta), 2.5 × 103 PFU/mL (Gamma), and 1.0 × 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 104 copies/mL, 9.0 × 105 copies/mL, 1.7 × 106 copies/mL, and 1.8 × 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods. IMPORTANCE Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Brasil , COVID-19/diagnóstico , Pandemias , Reino Unido , Coloide de Ouro
6.
Inorg Chem ; 61(39): 15547-15557, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36112414

RESUMO

The luminescence properties of two divalent europium complexes of the type Eu[N(SPPh2)2]2(THF)2 (1) and Eu[N(SePPh2)2]2(THF)2 (2) were investigated. The first complex, Eu[N(SPPh2)2]2(THF)2 (1), was found to be isomorphous with the reported structure of complex 2 and exhibited room temperature luminescence with thermochromic emission upon cooling. We found the complex Eu[N(SePPh2)2]2(THF)2 (2) was also thermochromic but the emission intensity was sensitive to temperature. Both room temperature and low temperature (100 K) single crystal X-ray structural investigation of 1 and 2 indicate geometric distortions of the metal coordination, which may be important for understanding the thermochromic behavior of these complexes. The trivalent europium complex Eu[N(SPPh2)2]3 (3) with the same ligand as 1 was also structurally characterized as a function of temperature and exhibited temperature-dependent luminescence intensity, with no observable emission at room temperature but intense luminescence at 77 K. Variable temperature Raman spectroscopy was used to determine the onset temperature of luminescence of Eu[N(SPPh2)2]3 (3), where the 615 nm (5D0 → 7F2 transition) peak was quenched above 130 K. The UV-visible diffuse reflectance of 3 provides evidence of an LMCT band, supporting a mechanism of thermally activated LMCT quenching of Eu(III) emitting states. A series of ten isomorphous, trivalent lanthanide complexes of type Ln[N(SPPh2)2]3 (Ln = Eu (3) Pr (4), Nd (5), Sm (6), Gd (7), Tb (8)) and Ln[N(SePPh2)2]3 (Ln = Pr (9), Nd (10, structure was previously reported), Sm (11), and Gd (12) for Q = Se) were also synthesized and structurally characterized. These complexes for Ln = Pr, Nd, Sm, and Tb exhibited room temperature luminescence. This study provides examples of temperature-dependent luminescence of both Eu2+ and Eu3+, and the use of soft-atom donor ligands to sensitize lanthanide luminescence in a range of trivalent lanthanides, spanning near IR and visible emitters.

7.
Front Cell Infect Microbiol ; 12: 898125, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909953

RESUMO

In Brazil, the production of KPC-type carbapenemases in Enterobacteriales is endemic, leading to widespread use of polymyxins. In the present study, 502 Klebsiella pneumoniae isolates were evaluated for resistance to polymyxins, their genetic determinants and clonality, in addition to the presence of carbapenem resistance genes and evaluation of antimicrobial resistance. Resistance to colistin (polymyxin E) was evaluated through initial selection on EMB agar containing 4% colistin sulfate, followed by Minimal Inhibitory Concentration (MIC) determination by broth microdilution. The susceptibility to 17 antimicrobials was assessed by disk diffusion. The presence of blaKPC, blaNDM and blaOXA-48-like carbapenemases was investigated by phenotypic methods and conventional PCR. Molecular typing was performed by PFGE and MLST. Allelic variants of the mcr gene were screened by PCR and chromosomal mutations in the pmrA, pmrB, phoP, phoQ and mgrB genes were investigated by sequencing. Our work showed a colistin resistance frequency of 29.5% (n = 148/502) in K. pneumoniae isolates. Colistin MICs from 4 to >128 µg/mL were identified (MIC50 = 64 µg/mL; MIC90 >128 µg/mL). All isolates were considered MDR, with the lowest resistance rates observed for amikacin (34.4%), and 19.6% of the isolates were resistant to all tested antimicrobials. The blaKPC gene was identified in 77% of the isolates, in consonance with the high rate of resistance to polymyxins related to its use as a therapeutic alternative. Through XbaI-PFGE, 51 pulsotypes were identified. MLST showed 21 STs, with ST437, ST258 and ST11 (CC11) being the most prevalent, and two new STs were determined: ST4868 and ST4869. The mcr-1 gene was identified in 3 K. pneumoniae isolates. Missense mutations in chromosomal genes were identified, as well as insertion sequences in mgrB. Furthermore, the identification of chromosomal mutations in K. pneumoniae isolates belonging from CC11 ensures its success as a high-risk epidemic clone in Brazil and worldwide.


Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana , Infecções por Klebsiella , Klebsiella pneumoniae , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil , Colistina/farmacologia , Colistina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Polimixinas/efeitos adversos , Polimixinas/farmacologia , Polimixinas/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/uso terapêutico
8.
Biochem Eng J ; 186: 108537, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35874089

RESUMO

Serological tests detect antibodies generated by infection or vaccination, and are indispensable tools along different phases of a pandemic, from early monitoring of pathogen spread up to seroepidemiological studies supporting immunization policies. This work discusses the development of an accurate and affordable COVID-19 antibody test, from production of a recombinant protein antigen up to test validation and economic analysis. We first developed a cost-effective, scalable technology to produce SARS-COV-2 spike protein and then used this antigen to develop an enzyme-linked immunosorbent assay (ELISA). A receiver operator characteristic (ROC) analysis allowed optimizing the cut-off and confirmed the high accuracy of the test: 98.6% specificity and 95% sensitivity for 11+ days after symptoms onset. We further showed that dried blood spots collected by finger pricking on simple test strips could replace conventional plasma/serum samples. A cost estimate was performed and revealed a final retail price in the range of one US dollar, reflecting the low cost of the ELISA test platform and the elimination of the need for venous blood sampling and refrigerated sample handling in clinical laboratories. The presented workflow can be completed in 4 months from first antigen expression to final test validation. It can be applied to other pathogens and in future pandemics, facilitating reliable and affordable seroepidemiological surveillance also in remote areas and in low-income countries.

9.
J Exp Med ; 219(9)2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35796685

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence of variants of concern that evade neutralization by antibodies elicited by prior infection or vaccination. Here we report on human neutralizing antibody and memory responses to the Gamma variant in a cohort of hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with Gamma SARS-CoV-2 spike protein, but neutralizing activity against Wuhan-Hu-1-1, Beta, Delta, or Omicron was significantly lower. Monoclonal antibodies from memory B cells also neutralized Gamma and Beta pseudoviruses more effectively than Wuhan-Hu-1. 69% and 34% of Gamma-neutralizing antibodies failed to neutralize Delta or Wuhan-Hu-1. Although Class 1 and 2 antibodies dominate the response to Wuhan-Hu-1 or Beta, 54% of antibodies elicited by Gamma infection recognized Class 3 epitopes. The results have implications for variant-specific vaccines and infections, suggesting that exposure to variants generally provides more limited protection to other variants.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Humanos , Glicoproteínas de Membrana/metabolismo , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral
10.
Front Immunol ; 13: 884760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844561

RESUMO

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation [spike protein with Alum + Poly(I:C)] in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.


Assuntos
COVID-19 , Vacinas Virais , Adjuvantes Imunológicos , Compostos de Alúmen , Animais , Linfócitos T CD8-Positivos , Vacinas contra COVID-19 , Humanos , Imunoglobulina G , Camundongos , Poli I-C , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
11.
J Pediatr Endocrinol Metab ; 35(8): 973-988, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-35850934

RESUMO

OBJECTIVES: To evaluate the effect of vitamin D supplementation on glycemic control in children and adolescents with T1DM. CONTENT: A systematic search was conducted of the Medline/PubMed, Web of Science, Embase, BVS/Lilacs, Cochrane Library, Scopus, Cinahl, Food Science, and FSTA databases. Two reviewers independently extracted article data and assessed quality. SUMMARY: A total of 1,613 eligible articles were retrieved, ten of which met the selection criteria: eight clinical trials, one retrospective cohort study, and one cross-sectional study. Regarding the cutoff points used to classify vitamin D status, most of the studies set deficiency at 25-hydroxyvitamin D <20 ng/mL, sufficiency at ≥30 ng/mL, and insufficiency as the interval between these values. Regarding intervention strategies, most used cholecalciferol for supplementation, but there was great variation in the dose and supplementation time. When evaluating the effect of vitamin D supplementation on HbA1c, a significant improvement in glycemic control was observed in 50% of the studies. However, only one of these studies was classified as being of positive methodological quality, with three having their quality classified as neutral and one as negative. OUTLOOK: There is yet no consistent evidence on the effect of vitamin D supplementation on glycemic control as an adjuvant in the treatment of children and adolescents with T1DM.


Assuntos
Diabetes Mellitus Tipo 1 , Deficiência de Vitamina D , Adolescente , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Suplementos Nutricionais , Controle Glicêmico , Humanos , Estudos Retrospectivos , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico
12.
EBioMedicine ; 75: 103774, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34959134

RESUMO

BACKGROUND: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 are important diagnostic tools. We assessed clinical performance and ease-of-use of seven Ag-RDTs in a prospective, manufacturer-independent, multi-centre cross-sectional diagnostic accuracy study to inform global decision makers. METHODS: Unvaccinated participants suspected of a first SARS-CoV-2 infection were recruited at six sites (Germany, Brazil). Ag-RDTs were evaluated sequentially, with collection of paired swabs for routine reverse transcription polymerase chain reaction (RT-PCR) testing and Ag-RDT testing. Performance was compared to RT-PCR overall and in sub-group analyses (viral load, symptoms, symptoms duration). To understandusability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. FINDINGS: 7471 participants were included in the analysis. Sensitivities across Ag-RDTs ranged from 70·4%-90·1%, specificities were above 97·2% for all Ag-RDTs but one (93·1%).Ag-RDTs, Mologic, Bionote, Standard Q, showed diagnostic accuracy in line with WHO targets (> 80% sensitivity, > 97% specificity). All tests showed high sensitivity in the first three days after symptom onset (≥87·1%) and in individuals with viral loads≥ 6 log10SARS-CoV2 RNA copies/mL (≥ 88·7%). Usability varied, with Rapigen, Bionote and Standard Q reaching very good scores; 90, 88 and 84/100, respectively. INTERPRETATION: Variability in test performance is partially explained by variable viral loads in population evaluated over the course of the pandemic. All Ag-RDTs reach high sensitivity early in the disease and in individuals with high viral loads, supporting their role in identifying transmission relevant infections. For easy-to-use tests, performance shown will likely be maintained in routine implementation. FUNDING: Ministry of Science, Research and Arts, State of Baden-Wuerttemberg, Germany, internal funds from Heidelberg University Hospital, University Hospital Charité - Universitätsmedizin Berlin, UK Department of International Development, WHO, Unitaid.


Assuntos
Antígenos Virais/imunologia , Teste Sorológico para COVID-19 , COVID-19 , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2/imunologia , Adulto , COVID-19/diagnóstico , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
13.
BMC Geriatr ; 21(1): 633, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736422

RESUMO

BACKGROUND: Postoperative delirium (POD) is a common complication of older people undergoing hip fracture surgery, which negatively affects clinical- and healthcare-related outcomes. Unfortunately, POD pathophysiology is still largely unknown, despite previous studies showing that neuroinflammation, neuroendocrine dysfunction, increased reactive oxidative stress (ROS), and endothelial dysfunctions may be involved. There is also evidence that many of the pathophysiological mechanisms which are involved in delirium are involved in sarcopenia too. This article describes the protocol of a pilot study to evaluate the feasibility of a larger one that will explore the pathophysiological mechanisms correlating POD with sarcopenia. We will analyse whether various biomarkers reflecting neuroinflammation, ROS, neuroendocrine disorders, and microvasculature lesions will be simultaneously expressed in in the blood, cerebrospinal fluid (CSF), and muscles of patients developing POD. METHODS: Two centres will be involved in this study, each recruiting a convenient sample of ten older patients with hip fracture. All of them will undergo a baseline Comprehensive Geriatric Assessment, which will be used to construct a Rockwood-based Frailty Index (FI). Blood samples will be collected for each patient on the day of surgery and 1 day before. Additionally, CSF and muscle fragments will be taken and given to a biologist for subsequent analyses. The presence of POD will be assessed in each patient every morning until hospital discharge using the 4AT. Delirium subtypes and severity will be assessed using the Delirium Motor Subtype Scale-4 and the Delirium-O-Meter, respectively. We will also evaluate the patient's functional status at discharge, using the Cumulated Ambulation Score. DISCUSSION: This study will be the first to correlate biomarkers of blood, CSF, and muscle in older patients with hip fracture.


Assuntos
Delírio , Fraturas do Quadril , Idoso , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Avaliação Geriátrica , Fraturas do Quadril/cirurgia , Humanos , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
14.
Virus Evol ; 7(2): veab078, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34642605

RESUMO

Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing A→U and decreasing G→A signatures. G→A mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host's innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.

15.
An Acad Bras Cienc ; 93(suppl 4): e20210204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614091

RESUMO

Phytomelanin is a mechanically hard, blackish, and inert substance rarely found in plants. In Asteraceae, this substance was historically associated with the Heliantheae alliance, but recent studies have observed it in unrelated groups as Heterocoma and Wunderlichia. During a taxonomic investigation, we found phytomelanin in cypselae of Lychnophora salicifolia an unusual feature in Vernonieae previously found only in Heterocoma. Furthermore, phytomelanin fills the intercellular spaces of the sclerenchymatic outer mesocarp in L. salicifolia. Our results doubt the (syn)apomorphy status in Heterocoma, suggest the phytomelanin may have not the same evolutionary significance in Lychnophorinae as in other tribes and proposes new perspectives for evolutionary studies in Asteraceae.


Assuntos
Asteraceae
16.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-461434

RESUMO

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid (Poly(I:C)) adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after one or two boosts. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation (spike protein with Alum + Poly(I:C)) in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.

18.
Ann Bot ; 127(2): 167-174, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32893847

RESUMO

BACKGROUND: A structure called the pleurogram makes up a large part of the seed coat of some species in subfamilies Caesalpinioideae and Mimosoideae of Fabaceae, but little is known about its function. It has been hypothesized that this structure acts as a hygroscopic valve during the maturation drying of seeds. However, a new hypothesis has recently emerged that proposes a distinct function for the pleurogram. SCOPE: Here, we provide an overview of the structure and function of the pleurogram, which is diverse and complex. This large structure can be dislodged, thereby creating a pathway for water entry into water-impermeable seeds. However, the pleurogram is non-functional as a pathway of water into the seed of some species. Thus, the evolutionary history of species with a pleurogram may be related to a loss/gain in its function. A complete model for the function of the pleurogram is proposed. CONCLUSIONS: The pleurogram may act on several stages of the seed, from maturation to germination. As a hygroscopic valve, it regulates dehydration of the seed during maturation. As a pathway for water entry into the seed, the pleurogram acts as a water gap in seeds with physical dormancy, thereby regulating dormancy break/germination. The occurrence of a pleurogram in several genera of legumes and Cucurbitaceae is confirmed. Single or multiple pleurograms can serve as (the) point(s) of water entry into seeds that do not otherwise have a hilar water gap.


Assuntos
Fabaceae , Germinação , Evolução Biológica , Dormência de Plantas , Sementes , Água
19.
J. Bras. Patol. Med. Lab. (Online) ; 57: e2252021, 2021. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1350879

RESUMO

RESUMEN Introducción La hemoterapia es una especialidad médica estructurada con diversas acciones orientadas a la calidad del componente sanguíneo producido y la seguridad tanto para el donante como para el paciente, además de integrarse directamente en el proceso asistencial. Los primeros indicadores de hemoterapia se crearon para orientar la dirección del Programa de Calidad de la Sangre de Brasil, pero, en el escenario de la hemoterapia, debemos considerar no solo la calidad de la sangre sino también la seguridad del paciente y el donante y las acciones de hemovigilancia. Objetivo Basado en el análisis de los datos disponibles en los distintos informes y registros publicados por la Agencia Nacional de Vigilancia Sanitaria de Brasil (Anvisa), el Ministerio de Salud de Brasil (MS) y la Coordinación General de Sangre y componentes Hemoderivados (CGSH) en los últimos cinco años, nos propusimos identificar algunas debilidades y riesgos en el proceso de transfusión y proponer el uso de una herramienta llamada matriz de indicadores, para priorizar indicadores con un enfoque en seguridad de las transfusiones. Metodología La selección de indicadores se basó en la construcción de una matriz de priorización, utilizando los ejes estratégicos definidos por la OMS, cuyo objetivo es controlar todo el ciclo de la sangre, incluido el proceso de transfusión. Resultados La selección de indicadores tiene como objetivo mejorar los procesos involucrados a lo largo del ciclo de la sangre, y el uso de la herramienta apunta a facilitar la elección de estos indicadores según el escenario de cada institución, desde un servicio de hemoterapia hasta una agencia de transfusión. Conclusión Estos indicadores pueden mejorar las prácticas y procesos de la transfusión sanguínea, así como optimizar la capacidad de gestión de cada servicio, independientemente de su complejidad. Además, sirven para mejorar continuamente la calidad, seguridad y eficiencia de los centros de hemoterapia.

20.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20231217

RESUMO

Prolonged infection of SARS-CoV-2 represents a challenge to the development of effective public health policies to control the COVID-19 pandemic. The reason why some people have persistent infection and how the virus survives for so long are still not fully understood. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during persistent infection. Thirty-three patients who remained RT-PCR positive in the nasopharynx for at least 16 days were included in this study. Complete SARS-CoV-2 sequences were obtained for each patient at two time points. Phylogenetic, populational, and computational analysis of viral sequences confirmed persistent infection with evidence for a transmission cluster in health care professionals that shared the same workplace. A high number of missense variants targeting crucial structural and non-structural proteins such as Spike and Helicase was found. Interestingly, longitudinal acquisition of substitutions in Spike protein mapped many SARS-CoV-2 predicted T cell epitopes. Furthermore, the mutational profiles observed were suggestive of RNA editing enzyme activities, indicating innate immune mechanisms of the host cell. Viral quasispecies analysis corroborates persistent infection mainly by increasing richness and nucleotide diversity over time. Altogether, our findings highlight a dynamic and complex landscape of host and pathogen interaction during persistent infection suggesting that the hosts innate immunity shapes the increase of intra-host diversity with possible implications for therapeutic strategies and public health decisions during the COVID-19 pandemic.

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