RESUMEN
The potential consequences of the COVID-19 outbreak are multifarious and remain largely unknown. Deaths as a direct result of the condition are already in the millions, and the number of indirect deaths is likely to be even higher. Pre-existing historical inequalities are compounded by the virus, driving increased rates of infection and deaths amongst people who use drugs and alcohol, those belonging to racial-ethnic minority groups, poorer communities, LBGTQ+ populations, healthcare workers, and other members of the care economy; all of whom are already at increased risk of adverse mental health effects. In this paper we suggest that a central role of mental health practitioners is advocacy: both for people who use psychiatric services and for those who, due to the effects of the pandemic, are at an increased risk of needing to do so.
Asunto(s)
COVID-19 , Psiquiatría , Brotes de Enfermedades , Etnicidad , Humanos , Salud Mental , Grupos Minoritarios , SARS-CoV-2RESUMEN
CONTEXT: Cardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery but is associated with acute, transient, renal dysfunction that has a negative impact on long-term survival. OBJECTIVE: To unravel the molecular pathogenesis of renal injury following CPB. DESIGN: To obtain insight into the pathogenesis of renal dysfunction following CPB, we performed a microarray analysis of renal gene expression in the rat. SETTING: University Medical Centre Groningen. INTERVENTION: Rats underwent CPB or a sham procedure for 60âmin and were sacrificed at 60âmin, 1 and 5 days after the procedure. MAIN OUTCOME MEASURES: Renal gene expression profile as determined by microarray analysis. RESULTS: Expression of 420 genes was significantly altered in CPB compared to the sham procedure, and in 407 genes, this was evident in the acute phase (60âmin) following CPB. Gene ontology analysis revealed 28 of these genes were involved in inflammatory responses, with high expression of genes downstream of mitogen-activated protein-kinase (MAP-kinase) signalling pathways. Potent inducers identified are from the interleukin-6 cytokine family that consists of interleukin-6 and oncostatin M (OSM), which signal through the gp130-cytokine receptor complex. The plasma concentration of interleukin-6 was hugely increased by CPB as measured by ELISA. Expression of genes downstream of these signalling pathways that lead to production of chemokines, adhesion molecules and molecules involved in coagulative pathways, was upregulated. CONCLUSION: CPB induces an acute and local inflammatory response in the kidney, which might contribute to renal injury. The signalling pathways involved identified by gene expression analysis may represent pharmacological targets to limit renal injury following CPB.
Asunto(s)
Puente Cardiopulmonar/efectos adversos , Inflamación/patología , Riñón/metabolismo , Transcriptoma , Animales , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Riñón/lesiones , Riñón/fisiopatología , Sistema de Señalización de MAP Quinasas , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Wistar , Transducción de Señal , Factores de TiempoRESUMEN
Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.
Asunto(s)
Bacterias/genética , Genoma Bacteriano/genética , Redes y Vías Metabólicas/genética , Archaea/genética , Archaea/metabolismo , Inteligencia Artificial , Histidina/metabolismo , Metano/metabolismo , Familia de Multigenes , Enfermedades Periodontales/microbiología , Fenotipo , Reproducibilidad de los ResultadosRESUMEN
Antigenic characterization of Anaplasma marginale isolates, by identifying conserved and variable epitopes of major surface proteins (MSP), is an important tool for vaccine development against this rickettsia. The B cell epitopes of A. marginale isolates from three microregions of the State of Pernambuco and one from the State of Mato Grosso do Sul, Brazil, were characterized by indirect fluorescent antibody technique (IFAT) and Western blot (WB) with 15 monoclonal antibodies (MAbs). The epitope recognized by MAb ANA22B1 (MSP-1a) was conserved by IFAT and WB (73-81 kDa). MSP-2 epitopes recognized by MAbs ANAO58A2 and ANAO70A2 were conserved by IFAT, while ANAO50A2 and ANA66A2 epitopes were polymorphic; in the WB, the MAbs ANAO50A2 and ANAO70A2 identified bands of 45 kDa only in the Pernambuco-Mata isolate. None of the isolates reacted with MAb ANAR75C2 (MSP-3). The MSP-4 epitope recognized by MAb ANAR76A1 was conserved by IFAT, as well as the MSP-5 epitope recognized by MAb ANAF16C1 by IFAT and WB (16 kDa). The MAbs ANAR17A6, ANAR83B3, ANAR94C1, ANAO24D5 and ANAR19A6 identified conserved epitopes by IFAT. MSP-1, MSP-2 and MSP-4, which previously showed partial protection in experimental trials, are also potential immunogens to be employed in Brazil, due to the B cell epitope conservation.
Asunto(s)
Anaplasma/inmunología , Variación Antigénica/inmunología , Antígenos Bacterianos/inmunología , Epítopos de Linfocito B/inmunología , Anaplasma/genética , Anaplasmosis/inmunología , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Variación Antigénica/genética , Antígenos Bacterianos/genética , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Western Blotting , Brasil , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Electroforesis en Gel de Poliacrilamida , Epítopos de Linfocito B/genética , Técnica del Anticuerpo Fluorescente IndirectaRESUMEN
O presente trabalho teve por objetivo estudar comparativamente as alteraçöes clínicas e hematológicas desencadeadas por isolados de Babesia bigemina das regiöes Sudeste, Nordeste e Norte do Brasil em bezerros Nelore infectados experimentalmente. Foram utilizados 18 bezerros com idade entre sete e nove meses, isentos de anticorpos contra Babesia sp. e criados livres de carrapatos. Três animais foram previamente inoculados com 2,0x10(9) eritrócitos parasitados (EP) para cada isolado. Os outros 15 bezerros foram subdivididos em três grupos de cinco animais, que foram subinoculados com 1,0x10(10) EP dos respectivos isolados. Foram avaliadas as alteraçöes clínicas e hematológicas por meio da determinação da parasitemia, do hemograma, do fibrinogênio plasmático, da contagem de reticulócitos, da análise descritiva da medula óssea e da fragilidade osmótica eritrocitária, no decorrer de 30 dias, perfazendo um total de sete momentos de observaçäo. O acompanhamento da resposta imunológica pelo teste de imunofluorescência indireta foi realizado diariamente até o 10º dia pós-inoculaçäo (DPI) e posteriormente no 15º, 20º, 25º e 30º DPI. Clinicamente, observou-se uma manifestaçäo muito branda da doença. Os achados laboratoriais revelaram baixos níveis de parasitemia; decréscimo nos valores do eritrograma; ausência de reticulócitos; diminuiçäo inicial na contagem total dos leucócitos, neutrófilos e linfócitos com posterior elevaçäo do número destas células; hipercelularidade da série eritrocítica e decréscimo da relaçäo mielóide:eritróide mais acentuada entre o 8º e 12º DPI e um aumento da fragilidade osmótica eritrocitária nos grupos inoculados com os isolados sudeste e nordeste. Nenhum dos três isolados de B. bigemina desencadeou a forma clínica característica da enfermidade, apesar de induzirem uma resposta imune humoral
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Animales , Bovinos , Babesia , BovinosRESUMEN
Antigenic characterization of Anaplasma marginale isolates, by identifying conserved and variable epitopes of major surface proteins (MSP), is an important tool for vaccine development against this rickettsia. The B cell epitopes of A. marginale isolates from three microregions of the State of Pernambuco and one from the State of Mato Grosso do Sul, Brazil, were characterized by indirect fluorescent antibody technique (IFAT) and Western blot (WB) with 15 monoclonal antibodies (MAbs). The epitope recognized by MAb ANA22B1 (MSP-1a) was conserved by IFAT and WB (73-81 kDa). MSP-2 epitopes recognized by MAbs ANAO58A2 and ANAO70A2 were conserved by IFAT, while ANAO50A2 and ANA66A2 epitopes were polymorphic; in the WB, the MAbs ANAO50A2 and ANAO70A2 identified bands of 45 kDa only in the Pernambuco-Mata isolate. None of the isolates reacted with MAb ANAR75C2 (MSP-3). The MSP-4 epitope recognized by MAb ANAR76A1 was conserved by IFAT, as well as the MSP-5 epitope recognized by MAb ANAF16C1 by IFAT and WB (16 kDa). The MAbs ANAR17A6, ANAR83B3, ANAR94C1, ANAO24D5 and ANAR19A6 identified conserved epitopes by IFAT. MSP-1, MSP-2 and MSP-4, which previously showed partial protection in experimental trials, are also potential immunogens to be employed in Brazil, due to the B cell epitope conservation
Asunto(s)
Animales , Bovinos , Anaplasma , Variación Antigénica , Antígenos Bacterianos , Epítopos de Linfocito B , Anaplasmosis , Anticuerpos Monoclonales , Variación Antigénica , Antígenos Bacterianos , Antígenos de Superficie , Western Blotting , Enfermedades de los Bovinos , Electroforesis en Gel de Poliacrilamida , Epítopos de Linfocito B , Técnica del Anticuerpo Fluorescente IndirectaRESUMEN
A molecular epidemiological study was performed with Babesia bigemina isolates from five geographical regions of Brazil. The genetic analysis was done with random amplification of polymorphic DNA (RAPD), repetitive extragenic palindromic elements-polymerase chain reaction (REP-PCR) and enterobacterial repetitive intergenic consensus sequences-polymerase chain reaction (ERIC-PCR) that showed genetic polymorphism between these isolates and generated fingerprinting. In RAPD, ILO872 and ILO876 primers were able to detect at least one fingerprinting for each B. bigemina isolate. The amplification of B. bigemina DNA fragments by REP-PCR and ERIC-PCR gave evidence for the presence in this haemoprotozoan of the sequences described previously in microorganisms of the bacterial kingdom. For the first time it was demonstrated that both techniques can be used for genetic analysis of a protozoan parasite, although the ERIC-PCR was more discriminatory than REP-PCR. The dendogram with similarity coefficient among isolates showed two clusters and one subcluster. The Northeastern and Mid-Western isolates showed the greatest genetic diversity, while the Southeastern and Southern isolates were the closest. The antigenic analysis was done through indirect fluorescent antibody technique and Western blotting using a panel of monoclonal antibodies directed against epitopes on the merozoite membrane surface, rhoptries and membrane of infected erythrocytes. As expected, the merozoite variable surface antigens, major surface antigen (MSA)-1 and MSA-2 showed antigenic diversity. However, B cell epitopes on rhoptries and infected erythrocytes were conserved among all isolates studied. In this study it was possible to identify variable and conserved antigens, which had already been described as potential immunogens. Considering that an attenuated Babesia clone used as immunogen selected populations capable of evading the immunity induced by this vaccine, it is necessary to evaluate more deeply the cross-protection conferred by genetically more distant Brazilian B. bigemina isolates and make an evaluation of the polymorphism degree of variable antigens such as MSA-1 and MSA-2
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Animales , Femenino , Bovinos , Genética , Polimorfismo GenéticoRESUMEN
Avaliaram-se as alteraçöes clínico-laboratoriais de seis bezerros Nelore, de ambos os sexos, inoculados experimentalmente com 10 elevado a 7 organismos viáveis de Trypanosoma vivax, isolados de bovinos da regiäo de Poconé, Estado de Mato Grosso. Os animais foram observados diariamente, durante 30 dias, quanto aos parâmetros de temperatura retal, volume globular (VG), parasitemia, produçäo de anticorpos, coloraçäo de mucosas, comportamento e apetite. Determinaram-se os níveis séricos de aspartato aminotransferase (AST), fosfatase alcalina (FA), gama glutamiltransferase (GGT), creatina kinase (CK), colesterol, uréia, creatinina, cálcio, fósforo, e o perfil eletroforético das proteínas séricas aos 4,8,12,16,23 e 30 dias pós-inoculaçäo (DPI). Durante os 6 meses seguintes, os animais foram observados semanalmente, avaliando-se a temperatura retal, o VG e a parasitemia. T.vivax foi evidenciado a partir do terceiro e quarto DPI em todos os bezerros e persistiu até 30§ DPI em cinco dos seis animais em estudo. Ocorreu um decréscimo significativo (p<0,05) do valor médio do VG (25 por cento) aos dez DPI. Os animais näo apresentaram qualquer alteraçäo no quadro clínico, bem como na avaliaçäo da bioquímica sérica durante o período experimental. A soroconversäo ocorreu aos 6 e 8 DPI, permanecendo todos os animais soropositivos nos 30 dias experimentais. Bovinos nelores jovens, infectados experimentalmente com T.vivax, foram capazes de estabelecer um equilíbrio na relaçäo hospedeiro-parasita
Asunto(s)
Masculino , Animales , Femenino , Hematología , Trypanosoma vivax , BovinosRESUMEN
A rapid conglutination test (RCT) with performance comparable to the indirect fluorescent antibody technique (IFAT) was developed to detect antibodies against Babesia bigemina (B. bigemina-RCT). The B. bigemina-RCT is a sensitive, specific, economical, and rapidly performed serological test suitable for field application or minimally equipped laboratories. This test had a sensitivity of 90.9 percent, and specificity of 97.6 percent, compared to IFAT, which showed for the same parameters respectively, 98.3 percent and 99.7 percent. The early detection of anti- B. bigemina immunoglobulins by RCT in experimental infections was nearly parallel to that of IFAT. Cross reactions were observed with sera from calves experimentally infected with Babesia bovis (1.8 percent) and with Anaplasma marginale (1.2 percent). RCT antigen prepared with non parasitized erythrocytes (negative antigen) showed 1.5 percent, 3.5 percent and 2.2 percent of positive reactions with sera from animals experimentally infected with B. bigemina, B. bovis and A. marginale. However, none of the sera from animals of endemic areas for babesia infection resulted in positive reactions with the negative antigen. Considering these results and shelf life over six months, the B. bigemina-RCT could be used for epidemiological surveys and evaluation of control measures against this species of Babesia.
Um teste rápido de conglutinação (TCR) com desempenho comparável a imunofluorencência indireta (IFI) foi desenvolvido para detectar anticorpos contra Babesia bigemina. O TCR-B.bigemina é um teste sorológico sensível, econômico e executável rapidamente; apropriado para condições de campo ou laboratórios com estrutura mínima. Este teste tem uma sensibilidade de 90,9% e especificidade de 97,6%, enquanto que a IFI apresentou para os mesmos parâmetros, respectivamente, 98,3% e 99,7%. Nas infecções experimentais a detecção de imunoglobulinas anti-B. bigemina pelo TCR foi aproximadamente a mesma da IFI. As reações cruzadas verificadas nos soros de bezerros experimentalmente infectados com Babesia bovis e Anaplasma marginale foram 1,8% e 1,2%, respectivamente. O antígeno preparado com eritrócitos não parasitados (antígeno negativo) apresentou 1,5%, 3,5% e 2,2% de reações positivas com os soros de animais infectados com B. bigemina, B. bovis e A. marginale. Entretanto, nenhum dos soros dos animais de áreas endêmicas para infecção de babésia resultaram em reações positivas com o antígeno negativo. Considerando estes resultados e o período de viabilidade do antígeno de TCR, acima de seis meses, possibilita o TCR-B. bigemina ser utilizado em levantamentos epidemiológicos e na avaliação das medidas de controle contra esta espécie de Babesia.