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The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease.To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B, and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients.The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases.Inflammasome genetic background contributes to individual response to SARS-CoV-2.

Objective and design: The heterogeneity of response to SARS-COV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stand out as a good novel candidate as severity factor for Covid-19 disease. Methods: To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B and IL18 single nucleotide variants (SNVs) in a cohort of 945 Covid-19 patients. Results: The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to Covid-19 severity, which could contribute to the excessive cytokine release reported in severe cases.

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Introducao Os transplantes hepaticos possuem um risco de sangramento intra-operatorio bastante variavel. Em alguns cenarios devido a coagulopatia associada a hepatopatia cronica e ao porte cirurgico complexo (antecedente de trombose de veia porta, hipertensao portal com colaterais, cirurgia abdominal previa entre outros), sangramentos de grande volume sao frequentes e podem requerer o uso de transfusoes sanguineas. O uso de recuperacao intra-operatoria tem o potencial de reduzir a necessidade de transfusao alogenica. Objetivos Analisar o impacto nas solicitacoes de transfusoes alogenicas nos pacientes submetidos a transplante hepatico de doador cadaver com o uso de recuperacao intra-operatoria. Material e metodos Estudo retrospectivo, com levantamento de dados baseados nos registros internos do Departamento de Hemoterapia. Foram analisados os transplantes hepaticos de doador cadaver realizados no periodo de janeiro de 2017 a julho de 2021 no Hospital Municipal Vila Santa Catarina (HMVSC), quanto aos dados demograficos dos pacientes, dados do procedimento de recuperacao intra-operatoria (RIO) e de consumo transfusional de concentrado de hemacias heterologo e autologo em dois grupos de pacientes de pacientes: com ou sem uso de RIO. Resultados Foram analisados 285 transplantes hepaticos realizados no periodo de janeiro de 2017 a julho de 2021 no Hospital Municipal Vila Santa Catarina (HMVSC). A mediana de idade dos pacientes foi 55 anos, sendo 68% dos pacientes do sexo masculino (193) e 32% do sexo feminino (92). 218 receberam transfusao de CH alogenica (76,5%), sendo a mediana de consumo transfusional de 2,0 unidades. Entre os 285 transplantes, 216 destes utilizaram a RIO (75,8%) e 69 nao utilizaram (24,2%) sendo as principais contra-indicacoes para uso de RIO: hepatocarcinoma celular e transplante com baixo risco de sangramento. Dos 216 pacientes que utilizaram RIO, a mediana de volume recuperado da RIO foi de 743,5 mL por procedimento (o que equivale a cerca de 2,7 unidades de CH autologo) e mediana de transfusao alogenica de 1 unidade de CH. Dos 69 pacientes que nao utilizaram RIO, a mediana de transfusao alogenica foi de 2 unidades de CH. Discussao No HMVSC, a maioria dos pacientes submetidos a transplante hepatico usou RIO (75,8% casos) e 76,5% dos pacientes recebeu pelo menos 1 unidade de CH alogenica. Alguns estudos demonstraram que a transfusao alogenica causa imunossupressao e impacta negativamente no desfecho clinico nos pacientes submetidos a transplante hepatico. Alem disso, ha o risco de exposicao a reacoes transfusionais (tais como infecciosas e imunologicas). A utilizacao de transfusao autologa e uma estrategia para diminuir a incidencia dos efeitos negativos da transfusao alogenica, assim evitando a utilizacao excessiva do sangue proveniente de doacoes, um recurso limitado, sendo o sangue recuperado na RIO uma boa estrategia transfusional. Na populacao estudada, o uso de recuperacao intra-operatoria minimizou o uso de CH alogenico, o que poupou o consumo de 2,7 unidades de CH. Conclusao O uso de recuperacao intra-operatoria minimiza o uso perioperatorio de CH alogenico, prevenindo a exposicao de transfusao alogenica e seus possiveis efeitos negativos.

Introdução: Em 2020 o mundo se depara com a maior crise sanitária da história causada pelo novo coronavírus SARS-CoV-2. Nesse momento de tamanha fragilidade muitos seguimentos foram afetados drasticamente e a necessidade de se reinventar tornou-se crucial. Os serviços hemoterápicos vivenciam uma queda expressiva dos estoques sanguíneos. Em nosso serviço essa redução das doações de sangue foi conduzida dia a dia com menor impacto uma vez que ocorreu, também, a diminuição das transfusões de sangue, porém, desde então não foi possível estabelecer o equilíbrio dos estoques sanguíneos e o cenário transfusional aumentou significativamente causando grande preocupação. Diante dos fatos implementamos a coleta externa como alternativa para suplementar o abastecimento sanguíneo e essa se mostrou uma forte aliada. Objetivos: Avaliar a viabilidade da implementação da coleta externa de sangue como complemento no suporte da manutenção do estoque sanguíneo do serviço de hemoterapia do hospital Albert Einstein. Materiais e métodos: Aperfeiçoamos nossos processos e estrutura para ampliar as coletas nesse modelo. Adquirimos novos equipamentos, aumentamos o quadro de colaboradores, criação de arte para envio aos doadores, desenvolvimento de infográfico para ajudar na comunicação com os critérios de aptidão do doador, implementação do agendamento via site, criação de formulário para visita técnica e check list para averiguação de pendências, além de todos os protocolos de segurança para bloquear o risco de contaminação. Resultados: No período compreendido entre julho 2020 a junho 2021 realizamos um total de 48 dias de coleta externa, em 18 locais diferenciados. Foram triados 2487 candidatos a doação e 1979 bolsas de sangue foram coletadas, 508 candidatos foram inaptos representando 20%. O ganho adicional com a coleta externa durante o período apurado foi de aproximadamente 17%. Nota-se boa adesão por parte dos doadores e uma excelente alternativa para aqueles que evitam realizar doação em ambiente hospitalar. Discussão: A pandemia fez o mundo se reinventar rapidamente e a coleta externa que já era implementada em alguns serviços não fazia parte do nosso dia a dia, assim, com a escassez de doadores direcionamos para esse modelo que tem dado bons resultados. A cada dia estamos aperfeiçoando os processos, realizando ajustes e melhorando toda a operação. A captação de novos locais proporcionará a médio prazo obter informações que ajudará a identificar o perfil de doadores e direcionará a ações mais eficazes. Esse ajuste também trará benefícios em relação ao descarte de produtos. Conclusão: A coleta externa tem ajudado os serviços hemoterápicos a equilibrar seus estoques sanguíneos e tem excelente aceitação por parte dos doadores de sangue. Certamente esse modelo de doação está se consolidando cada vez mais e levará os serviços a reverem suas estruturas.

Background Current evidence regarding COVID‐19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID‐19. Methods Prospective cohort including 102 patients with COVID‐19 transfused with ABO compatible CCP on days 0–2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect‐based virus neutralization test with SARS‐CoV‐2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)‐free days and the number of invasive mechanical ventilation‐free days. Results Both nAbs of CCP units transfused (p

BACKGROUND: Blood groups and anti-A isohemagglutinin may be involved in susceptibility to SARS-CoV-2 infection. MATERIALS AND METHODS: We retrospectively studied 268 COVID-19 convalescent plasma donors and 162 COVID-19 inpatients (total 430 subjects, confirmed by RT-PCR) and 2,212 healthy volunteer first-time blood donors as a control group. These were further divided into two groups: those with anti-A (blood types O and B) and those without it (types A and AB). Titres of nucleoproteins, and neutralizing SARS-CoV-2 antibody were measured in the convalescent plasma donors and inpatients. Multivariate logistic regression and non-parametric tests were applied. RESULTS: Persons having types O or B showed less infection prevalence than those of types A or AB (OR = 0·62, 95% CI 0·50-0·78; P

Introduction: The Zika Virus (ZIKV) is a single-stranded RNA genome virus, belonging to the family Flaviviridae, genus Flavivirus. Outbreaks around the world have demonstrated that the presence of asymptomatic viremic blood donors provides an increase in the risk of transfusion transmission (TT) and nucleic acid test (NAT) screening has been proposed to ensure the blood safety. This study implemented an “in-house” method to detect ZIKV RNA in blood sample donations. Methods: Primary plasma tubes are submitted to nucleic acid extraction on an automated platform. After extraction, the NAT set-up is performed in the robotic pipettor, in which an amplification mixture containing primers and probes for ZIKV and Polio vaccine virus (PV) are added in duplex as an internal control. The real-time polymerase chain reaction is then performed in a thermocycler, using the protocol established by the supplier. Results: From May 2016 to May 2018, 3,369 samples were collected from 3,221 blood donors (confidence coefficient 95%), of which 31 were considered false positive (0.92%), as they did not confirm initial reactivity when repeated in duplicates and 14 (0.42%) had their results invalid due to repeat failure in the internal control, 4 (0.12%), due to insufficient sample volume and 2 (0.05%), due to automatic pipettor failures. No Zika RNA reactive sample was identified. Conclusion: The test showed feasible to be incorporated into the blood screening routine. Our data do not indicate the need to screen for ZIKV RNA in Sao Paulo during the evaluated period. However, a generic NAT system covering a group of flaviviruses which are circulating in the region, such as DENV and YFV, among others, could be a useful tool.

Introdução: A participação dos neutrófilos como mediadores de infecção, trombose e neoplasia tem sido descrita em vários cenários. Além de seu papel na imunidade inata, sabe-se que os neutrófilos contribuem para ativação de inflamação, coagulação, imunossupressão através da formação de redes extracelulares de neutrófilos (NETs -neutrophil extracellular traps) em resposta a estímulos antigênicos e de ácidos nucleicos. Entretanto, pouco se sabe sobre o papel da NETose no cenário do transplante hepático, situação em que há um estado inflamatório persistente, exacerbado por vários eventos, inclusive transfusão de hemocomponentes. Ainda, sabe-se que os pacientes hepatopatas são bastante complexos do ponto de vista hemostático e a identificação de possíveis marcadores preditores de transfusão e hemoderivados potencialmente auxiliaria no manejo clínico destes pacientes. O objetivo deste estudo foi avaliar o papel de NETs como preditores de transfusão de hemocomponentes, bem como estabelecer uma correlação entre NETs e complicações em transplante hepático. Materiais e métodos: Foram quantificados DNA livre pela técnica de PicoGreen (dsDNAAssay Kit (ThermoFisherScientific, EUA) e H3 citrulinado por ELISA (clone 11D3, ELISA, Cayman), marcadores de remanescentes de NETs, no pré-operatório, intraoperatório e pós-operatório de 93 pacientes submetidos a transplante hepático em um hospital terciário em São Paulo-SP. Os pacientes foram seguidos desde a internação até a alta hospitalar e foram avaliados os seguintes desfechos clínicos: transfusão de hemocomponentes, uso de hemoderivados e antifibrinolíticos, rejeição, trombose, infecção e disfunção de órgãos. Resultados: Observamos uma ascensão dos níveis de H3 citrulinado e DNA livre do pré-operatório para o intraoperatório, com posterior declínio pré-alta hospitalar, de maneira estatisticamente significativa, (p < 0.0001), confirmando a ocorrência de NETOse exacerbada no intraoperatório do transplante hepático. Ainda, demonstramos que a liberação de NETs no intraoperatório foi preditora de óbito intra-hospitalar (OR = 1,168, CI 95% = 1,021-1,336, p = 0,024). Não se observou nenhuma associação entre NETose e transfusão, nem uso de hemoderivados. Entretanto, observou-se que a liberação de H3 citrulinado foi associada a menor uso de ácido tranexâmico durante o transplante (OR:0,824, CI95%0,705-0,964, p:0,016). Não foram observadas outras associações entre NETose no intraoperatório e demais desfechos clínicos negativos (rejeição, trombose, infecção ou disfunção de órgãos). Conclusão: Não foi possível estabelecer correlação entre NETose e necessidades transfusionais nos pacientes submetidos a transplante hepático. Entretanto, o presente estudo evidenciou uma associação significativa entre NETose e óbito intra-hospitalar. Dada a relevância da associação entre NETose e óbito e o papel central dos NETs na inflamação do transplante hepático, consideramos que NETs podem ser potenciais biomarcadores de inflamação nestes pacientes. Ainda, o desenvolvimento de terapêuticas focando na inibição de NETose poderia ser uma estratégia plausível para redução de efeitos deletérios da inflamação exacerbada inerente ao transplante. Mais estudos são necessários a fim de confirmar esta hipótese.

Introdução: Sabe-se que a infecção por SARSCOV2 é notavelmente marcada por fenômenos inflamatórios exacerbados e envolvimento tanto da imunidade inata quanto adaptativa, por meio de respostas imunes complexas. Um dos mecanismos descritos na fisiopatogenia da COVID19 é a formação de NETs (neutrophil extracelullar traps), redes extracelulares de neutrófilos, responsáveis em parte pela injúria tecidual e microtrombos que acometem os pacientes infectados com formas graves de COVID19. A transfusão de plasma convalescente tem sido utilizada como terapêutica alternativa no tratamento da COVID19. Entende-se que o benefício desta terapêutica seria baseado na presença de anticorpos neutralizantes, que seriam capazes de bloquear a progressão da infecção viral. O objetivo deste estudo foi avaliar o impacto na formação de marcadores de NETs em pacientes com formas graves de COVID 19 que receberam transfusão de plasma convalescente. Materiais e métodos: Foram avaliados 55 pacientes com pneumonia grave por COVID19 de acordo com critérios da Organização Mundial de Saúde, admitidos para tratamento em Unidades de Terapia intensiva em um hospital terciário em São Paulo-SP. Foram coletadas amostras dos pacientes na admissão do estudo (D0= dia da transfusão de plasma convalescente), D5 e na alta hospitalar. Foram mensurados os marcadores de NETs (H3 citrulinado por ELISA (clone 11D3, ELISA, Cayman) e DNA livre pela técnica de PicoGreen (dsDNAAssay Kit (ThermoFisherScientific, EUA) no D0, D5 e alta dos pacientes. As transfusões de plasma convalescente ocorreram entre os dias D0 e D2, em doses de 300 a 600 ml e foram transfundidos plasmas com títulos de anticorpos neutralizantes (NAbsT) superiores a 160, mensurados pela técnica de CPE-VNT (Cytopathic effect-based virus neutralization test CPE-VNT -SARS-CoV-2 GenBank MT126808.1). Foram também mensurados os títulos de anticorpos neutralizantes dos pacientes (NabsP)antes da transfusão de plasma no D0. Os testes realizados para verificar possíveis associações entre títulos de anticorpos transfundidos, características dos pacientes e variação dos marcadores de NETs no D0 e D5 foram correlações de Spearman. Resultados: Verificamos um aumento nos níveis de H3 citrulinado no D0 para o D5 e posterior queda do D5 para a alta, de maneira estatisticamente significativa (p = 0,025). O mesmo ocorreu com os níveis de DNA livre, porém sem significância estatística (p = 0,065). Ao analisar os fatores envolvidos na expressão dos marcadores de NETose do D0 para o D5, não se estabeleceu nenhuma associação entre níveis de anticorpos neutralizantes transfundidos (NabsT) (p=0,714) nem níveis basais de anticorpos produzidos pelos próprios pacientes (NabsP) antes da transfusão do plasma convalescente. Ainda, não encontramos quaisquer associações entre demais variáveis analisadas (idade, peso, escore SOFA Severity Organ Failure Assessment, sexo, presença de comorbidades e início de sintomas até a transfusão) e variação de marcadores de NETose nos pacientes incluídos no estudo. Conclusão e discussão: Nesta análise, a transfusão de plasma convalescente não teve nenhum impacto nos marcadores de NETose de pacientes com formas graves de COVID que receberam transfusão de plasma convalescente. Não se observou nenhuma associação entre anticorpos neutralizantes transfundidos e expressão de NETs entre D0 e D5. Neste estudo, a expressão de NETs durante o curso da doença variou de maneira independente de todas as variáveis estudadas.

Introducao A transfusao de plasma convalescente tem sido utilizada como terapeutica alternativa no tratamento de COVID19 nos ultimos meses. Avaliamos o impacto dos anticorpos neutralizantes produzidos pelos pacientes e dos anticorpos presentes nas unidades transfundidas na reducao da carga viral em pacientes em tratamento hospitalar de COVID19. Materiais e metodos Foram avaliados consecutivamente 29 pacientes admitidos para tratamento hospitalar de COVID19 em um unico centro. Doses de 300 a 600 ml de plasma convalescente foram administradas ao longo de 2 dias. Foram coletados swabs nasais a cada 48 h a partir do D0 (dia de transfusao de plasma convalescente) ate a alta hospitalar, a fim de determinar a carga viral por digital droplet PCR (ddPCR) dos alvos N1 e N2 do gene N (nucleocapsideo) para analise de reducao de carga viral, sendo considerado o numero de copias virais por 1000 celulas presente na amostra. Mensuramos os titulos de anticorpos neutralizantes (cytopathic effect-based virus neutralization test -SARS-CoV-2 GenBank MT126808.1) dos pacientes (NAbsP) antes da transfusao (D0) e titulos de anticorpos neutralizantes das unidades de plasma transfundidas (NAbsT). Para analise de associacao entre NAbsP e reducao de carga viral, os pacientes foram divididos em dois grupos de acordo com o status de NAbsP no D0: titulo de NabsP inferior a 80 e titulo de NabsP igual ou superior a 80. Para esta analise, foi utilizado o teste de Mann-Whitney . Para verificar a associacao entre NAbsT e reducao de carga viral, os pacientes foram divididos em tres grupos: aqueles que receberam transfusao de plasma convalescente com titulo de NAbsT ate 160, titulo de NAbsT entre 160-640 e NAbsT superior a 640. Para esta analise, foi utilizado o teste de Kruskall-Wallis. Resultados Pacientes com baixos titulos de neutralizantes a admissao (NAbsP inferior a 80) apresentaram reducao de carga viral significativamente maior (p=0,009) que pacientes com NAbsP igual ou superior a 80. Com relacao ao impacto da transfusao de plasma, observou-se que quanto maior o titulo de anticorpos neutralizantes transfundidos maior foi a reducao da carga viral; porem, tal achado nao apresentou significância estatistica (p = 0,528). Discussao O combate e eliminacao da viremia atraves dos anticorpos neutralizantes presentes no plasma convalescente compreende uma das justificativas da sua aplicacao como terapia alternativa para COVID19. Contudo, estudos previos demonstraram resultados contraditorios em relacao ao seu impacto no clearance viral. Na presente casuistica, pacientes com baixos titulos de anticorpos neutralizantes apresentaram maior reducao de carga viral apos a transfusao de plasma convalescente do que pacientes com altos titulos. Pacientes que ja apresentavam titulos elevados de neutralizantes parecem nao se beneficiar da transfusao de plasma no que se refere a reducao de carga viral. A estratificacao dos pacientes de acordo com os niveis basais de anticorpos neutralizantes parece ser um ponto importante a ser discutido no tratamento de COVID19 com plasma convalescente e fornece uma explicacao plausivel para os resultados controversos previamente observados.

INTRODUCTIONCOVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous.MATERIAL AND METHODSWe describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBankMT126808.1).RESULTSForty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p= 0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (pDISCUSSION/CONCLUSIONDespite the study limitations, our data have shown an association between patients’ previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.

To investigate the impact of stress at the SiO2/SiC gate interface on the channel mobility of 4H-SiC trench MOSFETs, we fabricated trench MOSFETs with two variations of stress in the channel region by changing the deposition temperature of polycrystalline silicon used for gate electrodes. The results found that effective mobility was enhanced by several dozen MPa of tensile stress toward [ 1 1 ¯ 00 ] induced by the polycrystalline silicon. Based on the temperature dependence of mobility, all scattering mobilities were enhanced. It was supposed that the electron effective mass decreased because of tensile stress induced at the channel region.

BACKGROUND Although Hematopoietic Stem Cells (HSC) donation through bone marrow (BM) and peripheral blood (PB) are usually safe procedures, adverse events are expected. One of the most common events especially among BM donors (BMD) is the development of anemia. To protect the BMD and preserve the hemoglobin levels, many centers collect autologous pre-procedure blood, but the actual benefits of this procedure is controversial. METHODS AND MATERIALS This study analyzed retrospectively data to observe what factors may influence the occurrence of post-donation anemia and also evaluate the relevance of autologous red blood cell pre procedure donation (PAD). RESULTS The development of immediately post donation anemia (IP) was higher in BMD than in PB donors (64.2% BMD and 10.7% PBD, P

Hydroxyoctadecadienoic acids (HODEs) are produced by oxidation and reduction of linoleates. There are several regio- and stereo-isomers of HODE, and their concentrations in vivo are higher than those of other lipids. Although conformational isomers may have different biological activities, comparative analysis of intracellular function of HODE isomers has not yet been performed. We evaluated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ), a therapeutic target for diabetes, and analyzed PPARγ agonist activity of HODE isomers. The lowest scores for docking poses of 12 types of HODE isomers (9-, 10-, 12-, and 13-HODEs) were almost similar in docking simulation of HODEs into PPARγ ligand-binding domain (LBD). Direct binding of HODE isomers to PPARγ LBD was determined by water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiments. In contrast, there were differences in PPARγ agonist activities among 9- and 13-HODE stereo-isomers and 12- and 13-HODE enantio-isomers in a dual-luciferase reporter assay. Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products.

Background Coronavirus disease 2019 (COVID‐19) convalescent plasma (CCP) collection began in two Brazilian hospitals for treatment of severe/critical patients. Methods and Materials Mild/moderate COVID‐19 convalescents were selected as CCP donors after reverse transcription polymerase chain reaction (RT‐PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and absence of symptoms for ≥14 days plus (a) age (18‐60 years), body weight greater than 55 kg; (b) immunohematological studies; (c) no infectious markers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T‐lymphotropic virus‐1/2, Chagas and syphilis infection; (d) no HLA antibodies (multiparous); (e) second RT‐PCR (nasopharyngeal swab and/or blood) negativity; (f) virus neutralization test (cytopathic effect–based virus neutralization test neutralizing antibody) and anti–nucleocapsid protein SARS‐CoV‐2 IgM, IgG, and IgA enzyme‐linked immunosorbent assays. Results Among 271 donors (41 females, 230 males), 250 presented with neutralizing antibodies. Final RT‐PCR was negative on swab (77.0%) or blood (88.4%; P = .46). Final definition of RT‐PCR was only defined at more than 28 days after full recovery in 59 of 174 (33.9%) RT‐PCR –ve, and 25/69 RT‐PCR +ve (36.2%; 13 between 35 and 48 days). Neutralizing antibody titers of 160 or greater were found in 63.6%. Correlation between IgG signal/cutoff of 5.0 or greater and neutralizing antibody of 160 or greater was 82.4%. Combination of final RT‐PCR –ve with neutralizing antibody ≥160 was 41.3% (112/271). Serial plasma collection showed decline in neutralizing antibody titers and IgA levels (P

The beneficial health effects of edible sea urchin consumption in mice fed a normal (ND) or high-fat diet (HFD) were investigated in this study. Notably, sea urchin-administered (250, 500, 1000 mg/kg) mice exhibited lower body, liver, and visceral fat weights, lower plasma levels of aspartate aminotransferase and alanine aminotransferase, and lower hepatic triacylglycerol levels than those fed carboxymethyl cellulose (CMC). Despite the high levels of cholesterol found in sea urchins, intake of these organisms had no effect on plasma cholesterol levels among the mice tested. Additionally, sea urchin consumption resulted in enhanced levels of arachidonic acid and docosahexaenoic acid within mouse livers. Lastly, mice fed HFD with sea urchin (500 mg/kg) exhibited increased mRNA expression of uncoupling protein-1 within brown adipose tissue, compared with those fed HFD with CMC. In conclusion, consumption of sea urchin might provide a protective effect against the development of obesity and/or nonalcoholic fatty liver disease.

Introdução: A participação de NETs (neutrophil extracellular traps- NETs- redes extracelulares de neutrófilos) na fisiopatogenia da COVID19 já foi descrita, especialmente nos casos graves de infecção por SARSCoV2, em que se destacam a inflamação sistêmica e imunotrombose culminando com injúria tecidual e insuficiência respiratória. Sabe-se que o estado protrombótico já nas fases iniciais da COVID19 deve-se em parte à formação de NETs em resposta à inflamação sistêmica desencadeada pela infecção viral Avaliamos 55 casos de pacientes com diagnóstico de pneumonia grave por COVID19 e mensuramos marcadores de NETose à admissão hospitalar e alta, a fim de identificar associações entre NETs e melhora clínica. Materiais e métodos: Avaliamos marcadores de NETs (H3 citrulinado por ELISA (clone 11D3, ELISA, Cayman e DNA livre pela técnica de PicoGreen (dsDNAAssay Kit (ThermoFisherScientific, EUA) no D0 (admissão no protocolo),D5 e alta em 55 pacientes com diagnóstico de pneumonia grave por SARSCoV2 (de acordo com os critérios da Organização Mundial de Saúde, definida por saturação em ar ambiente < ou igual a 93%, e/ou frequência respiratória igual ou superior a 30), admitidos à Unidade de Terapia Intensiva (UTI) em um hospital terciário em São Paulo, SP. O acompanhamento desses pacientes foi feito desde a admissão até a alta, a fim de correlacionar NETs no D0 (dia de inclusão no protocolo) e melhora clínica (definida por redução de 2 ou mais pontos na escala ordinal de gravidade da Organização Mundial de Saúde) desde a admissão até o D14 de internação hospitalar. Para as análises simples, foram realizados testes de MannWhitney e t de student e para as análises múltiplas, foram realizadas regressões logísticas. Resultados: Observamos que os níveis de H3 citrulinado sofrem uma ascensão do D0 para o D5, com posterior queda no momento alta, de maneira estatisticamente significativa (p = 0,025); evidenciando que a formação de NETs e sua queda acompanham o curso clínico da COVID19. Nas análises univariadas, observou-se associação significativa entre níveis de H3 citrulinado no D0 e melhora clínica (p=0.03), sendo que pacientes com melhora clínica têm níveis mais baixos de H3 citrulinado do que pacientes sem melhora clínica. Outras variáveis preditoras de melhora clínica nesta análise foram idade (p = 0.014) e escore SOFA (Sequential Organ Failure Assessment) no D0 (p < 0.001). Entretanto, nas análises múltiplas, apenas o score de SOFA (OR = 0,2, IC95%:0,05-0,84, p = 0.028) manteve esta associação. Discussão e conclusão: A associação entre NETs e fisiopatologia da COVID19 já foi descrita em alguns cenários, bem como correlacionados os marcadores de NETose à gravidade da doença. Os achados do presente estudo sugerem que a formação de NETs acompanha o curso clínico da COVID19. A intensidade da NETose no início da doença parece ser um parâmetro preditor de melhora clínica, porém, são necessários mais estudos para afirmar esta hipótese.

Background: Transfusion of blood products during orthotopic liver transplantation (OLT) is associated with increased morbidity and mortality. Although risk factors associated with intraoperative transfusion requirements have been widely assessed, published data on the prediction of postoperative transfusion requirements are sparse. Objectives: The aim of this study was to evaluate risk factors for postoperative allogeneic transfusion requirements in OLT. Methods: Clinical characteristics and intraoperative parameters of 645 consecutive adult patients undergoing OLT were retrospectively reviewed. Multivariate logistic regression was used to determine the main determinants for postoperative transfusion requirements. Results: Determinants of postoperative transfusion requirements of any blood product in the postoperative period were the number of blood products transfused in the intraoperative period (OR 1.17, 95% CI 1.08–1.28), warm ischemia time (OR 1.05, 95% CI 1.02–1.08), MELD score (OR 1.05, 95% CI 1.01–1.08) and hepatocellular carcinoma (OR 0.45, 95% CI 0.28–0.72). A dose-dependent effect between the number of units transfused in the intraoperative period and transfusion requirements in the postoperative period was also observed. The relative risk of postoperative allogeneic transfusion of any blood component was 5.9 (95% CI 3.4–10.4) for patients who received 1–2 units in the intraoperative period, 7.3 (95% CI 3.6–14.7) for those who received 3–5 units in the intraoperative period, and 11.1 (95% CI 4.7–26.4) for those who received 6 or more units, when compared to no intraoperative blood transfusion. Conclusion: Our study demonstrated an association between intraoperative transfusion and warm ischemia time with postoperative transfusion requirements. The identification of risk factors for transfusion in the postoperative period may improve management of these patients by increasing awareness to bleeding complications in this high-risk population and by expanding hemostasis monitoring to the postoperative period.

Background Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34+ collection yield and efficiency, and thawed HSC infusion side effect occurrence. Patients and methods We evaluated data from 361 patients who had undergone autologous PBSC transplant. Large volume leukapheresis was the method for PBSC collection. Complete Blood Count and CD34+ cell enumeration were performed in the preapheresis PB and the apheresis product sample. The PBSC grafts were submitted to non-controlled rate freezing after addition of 5% DMSO plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft was thawed in a 37°C water bath and then infused without further manipulation. Results The CD34+ yield was associated with preapheresis PB CD34+ count and immature granulocyte count. The PBSC CE was negatively correlated with preapheresis white blood cell (WBC), immature granulocyte and granulocyte count. The leukapheresis product total nucleated cell (TNC) and granulocyte content was correlated with the thawed graft infusion side effect occurrence. Conclusion This study has shown that preapheresis PB WBC and granulocyte counts were associated with leukapheresis CE. Additionally, the leukapheresis product TNC and granulocyte content was correlated with thawed graft infusion side effect occurrence.

Introduction Currently the ideal stem cell donor is a fully matched HLA sibling; nonetheless, an elderly patient has a high probability of an also aging donor. Age has been related to worse transplant outcomes, mainly due to the higher incidence of acute and chronic GVHD and higher mortality rates when compared to patients performing transplantation with younger donors, in addition to possible comorbidities that may make them ineligible for donation. Objectives Considering the excellent results of transplants with haploidentical donors, which are comparable to those obtained with fully matched donors, the present study aims at assessing which would be the best donor for the patient witch has a fully matched sibling of 50 years of age and older and a younger haploidentical child. Methods This is a consecutive retrospective descriptive observational epidemiological study involving all patients who underwent hematopoietic progenitor cell transplantation with a fully matched or partially matched (haploidentical) related donor during the period from January 2010 to October 2017. Overall survival of patients aged 50 years or older was the primary outcome of the study. Results An amount of 47 patients was included in the study. In 72% the diagnosis was acute myelogenous leukemia or myelodysplastic syndrome.Regarding the compatibility, in 31 (65.9%) of the procedures the donor was fully matched and in 16 (34.1%) the donor was haploidentical. The mean age of the patients was 63 years in both groups, but the mean age of donors was significantly higher among the fully matched donors, who were on average 60 years with a range between 32 and 82. All of these donors were siblings of the receptor. About the haploidentical donors, the mean age was 37 years, ranging from 21 to 66 years, and 87% were children of the recipient. We did not observe a statistically significant difference in overall survival between patients whose donor was fully matched or haploidentical. The age of the donor ( The time of hospitalization of patients submitted to haploidentical transplantation was greater than that patients whose donor was fully matched (69.6 days and 36.7 days respectively, p = 0.001). Conclusion The results obtained in the study demonstrate the non-inferiority of the donor haploidentico in relation to the fully matched donor for patients aged 50 years or more.

Background Accurate prediction of stem cell yield is important for planning leukapheresis procedures. A formula has been published (Pierelli et al., Vox Sang 2006;91:126-34) to estimate the CD34+ dose collected on the first day of leukapheresis that was based on the preapheresis peripheral blood (PB) CD34+ counts, the blood volume processed, and the donor's weight. The aim of this study was to assess the predictive value of this formula. Study design and methods Data were retrospectively collected on 1126 consecutive PB stem cell harvests conducted at five institutions. Information on age, sex, diagnosis, weight, preapheresis absolute peripheral CD34+ count, total blood volume processed, and CD34+ cells harvested per kilogram of body weight on the first day of apheresis was collected. Results Among donors at least 18 years old, Pearson's correlation coefficient (r) between actual yield (AY) and predicted yield (PY) was 0.76. To characterize this correlation, AY and PY were classified as being within the conventionally acceptable CD34+ doses (>2 × 10(6) -5 × 10(6) cells/kg), below this range (≤2 × 10(6) cells/kg), or above it (>5 × 10(6) cells/kg). The positive predictive value (PPV) of PY was estimated considering the distribution of AY as the "gold standard." PPV was relatively high for PY of more than 5 × 10(6) cells/kg (85%), moderate for PY of not more than 2 × 10(6) cells/kg (72%), and low for PY more than 2 × 10(6) to 5 × 10(6) cells/kg (56%). A consistent pattern was observed within institutions. Conclusion The formula of Pierelli et al. is associated with a PPV that is high, moderate, and relatively low for the corresponding predicted CD34+ doses.

Raman and powder X-ray measurements were performed for high temperature and high pressure phase I of Rb3H(SO4)2 up to 5 GPa and 540 K. We determined phase I to be a trigonal— R 3 ¯ m structure. Proton conductivity in phase I increased with pressure as previously reported. We measured the change in the hydrogen bonding state and the lattice parameters of phase I against pressure and found that the proton conductivity increased despite the strengthening of hydrogen bonding. The reason was that the interlayer hydrogen bonds were formed dynamically as the pressure increased, and the hydrogen bonds became an additional proton conduction path along the interlayer direction.

In Japan and Korea, outbreaks of scuticociliatosis have frequently occurred in Japanese flounder, Paralichthys olivaceus. Morphological observations and small subunit rRNA gene sequences have shown that the causative agent of scuticociliatosis in the flounder is Miamiensis avidus (syn. Philasterides dicentrarchi). In this study, we elucidated the antigenic differences between six Japanese M. avidus isolates as an initial step toward developing an effective vaccine against the disease. Four Japanese flounder isolates (IyoI, Nakajima, JF05To and Mie0301 isolates), one spotted knifejaw, Oplegnathus punctatus, isolate (SK05Kyo), and one ridged-eye flounder, Pleuronichthys cornutus, isolate (RF05To) were subjected to serological analysis. Antisera against IyoI, SK05Kyo, Nakajima and Mie0301 isolates were raised in rabbits and used for immobilization assays and Western blotting. Immobilization assays showed that the six isolates could be divided into three groups, tentatively designated serotype I for IyoI, JF05To, RF05To, SK05Kyo, serotype II for Nakajima and serotype III for Mie0301. Western blotting results supported these three serotypes, with marked similarities in the banding profiles of IyoI, JF05To, RF05To and SK05Kyo isolates, which were distinct from the Nakajima and Mie0301 isolates. Three isolates, IyoI, Nakajima and Mie0301 that were selected as representatives of each serotype, were highly pathogenic to Japanese flounder by experimental infection. Based on these findings, we propose that there are at least three M. avidus serotypes in Japan.

The crystal structure of the binary clathrate hydrate of methane (CH4) and ethanol was identified by powder X-ray diffraction. Raman spectroscopic measurements were also performed. Because hydrogen bonding between the water and ethanol molecules likely affects the hydrate formation and its stability, the role of ethanol for hydrate formation and its stability is important for a further understanding of the guest−host interactions in complex inclusion compounds. In this study, we provide evidence for the occupation of ethanol with CH4 in a structure II hydrate, whereas the ethanol is one of the inhibitors for hydrate formation. The cage occupancies of CH4 and ethanol as guest molecules within the hydrate cages was also estimated. It is shown that hexakaidecahedral (51264) cages were occupied by not only ethanol, but also CH4, even though a sufficient number of ethanol molecules existed in the current hydrate-forming system.

The development of RBC autoantibodies resulting from or associated with allogeneic blood transfusions is not an easily determined complication of RBC transfusions. This report discusses one patient who developed RBC autoantibodies in association with an allogeneic blood transfusion and alloimmunization leading to a temporary bystander immune hemolysis. A 72-year-old woman was hospitalized as a result of severe anemia and received two units of ABO- and D-compatible RBCs. She had a history of two pregnancies 40 years before, but no history of RBC transfusion, and her antibody screen was negative. On the tenth day after transfusion her hemoglobin dropped, and alloanti-c was identified in her serum and eluate. At this time she received another two units of compatible blood according to her phenotype (group O, R1R1, K:-1). After 48 hours, she developed joint pain, pyrexia, and hemoglobinuria, and her Hb dropped from 9.2 g/dL to 5.3 g/dL. The direct antiglobulin test was positive, an IgG autoantibody was present in the eluate, and the antibody investigation revealed the presence of anti-Jkb in addition to the previously identified alloanti-c. Her genotype was determined, and, based on the findings, two additional units were selected, found to be compatible, and transfused without incident. Transfusions were discontinued, and she was treated with IVIG and corticosteroids. Her Hb increased to 9.7 g/dL, and the patient made an uneventful recovery. It was concluded that transfusion of incompatible RBCs induced the formation of an autoantibody in this patient, resulting in lysis of bystander RBCs. The need for additional blood transfusion was successfully avoided by treatment with IVIG, steroid therapy, and rituximab. Immunohematology 2009;25:9–12.

Proton–deuteron mutual diffusion in a CsHSO4/CsDSO4 solid at 373 K was examined up to 3 GPa by an infrared mapping measurement. Phases HPHT1 and HPHT2 appeared at 1.5 and 2.3 GPa, respectively, after heating. These phases were found to be stable at room temperature, while phase IV, which appeared on compression at room temperature, was metastable. The pressure dependence of the proton–deuteron mutual diffusion coefficient was determined from the temporal change in the deuteron distribution of the solid. The coefficient decreased from 7×10−16 to 1×10−16 m2/s during the transition from phase II to HPHT1 at 1.5 GPa, and showed no significant change during the transition to phase HPHT2. These results suggested that in addition to the hydrogen bond length, other structural factors might also have had an influence on the rate of diffusion.

We present the results of electrochemical and structural investigations of several carbon materials: carbon blacks AD 100 and XC 72, ultradisperse diamond (UDD), multiwalled nanotubes (MWNT), various types of filament-like carbon materials (CFC series), and similar carbon materials promoted with cobalt tetra(para-methoxyphenyl) porphyrin (CoTMPhP) pyropolymer (PP). The electrochemical studies were performed at room temperature in 0.5 M H2SO4 by using a rotating disk electrode (RDE), a rotating ring-disk electrode (RRDE) (a thin layer of test material was applied onto the disk electrode), and a floating electrode. Structural characterization of initial and promoted carbon materials involved the determination of specific surface area by the BET method and by the polarization capacitance from cyclic voltammograms, and the particle morphology and dimensions by the transmission electron microscopy (TEM) method. The study of kinetics and mechanism of oxygen electroreduction on carbon materials promoted with CoTMPhP PP showed that the catalysts based on carbon materials of CFC and UDD series possess high specific activity in this reaction and high selectivity with respect to oxygen reduction to water. These catalysts are superior to the catalysts, in which carbon blacks AD 100 and XC 72 are used as the supports, in the specific activity.

The crystal structures of three phases of Cs 5 H 3 (SO 4 ) 4 · x H 2 O–a low-temperature phase (LT phase), a room-temperature phase (RT2 phase), and an intermediate phase (RH phase)–have been determined from powder X-ray diffraction data measured at 90 – 450 K. The structures of the LT, RT2, and RH phases were orthorhombic Cmcm ( a = 6.304 A; b = 10.388 A; c = 29.499 A), triclinic P -1 ( a = 6.248 A; b = 6.187 A; c = 14.833 A; α = 92.08°; β = 88.86°; γ = 121.15°), and trigonal P 3¯ m 1 ( a = 6.233 A; c = 14.788 A), respectively. The crystal structures of the hydrated and anhydrous forms in the usual room-temperature phase (RT phase) were also analyzed; reduction in the length of the a -axis was observed upon the loss of crystalline water, whereas the length of the c -axis remained constant. These results suggest that shrinkage in the a direction of the anhydrous form prevented reorientation of its SO 4 tetrahedra, resulting in slower proton diffusion [K. Suzuki and S. Hayashi, Phys. Rev. B 74 (2006) 134303] than that in the hydrated form. These findings are consistent with a proton transport mechanism in which SO 4 reorientation is the rate-determining step.

Infrared spectra of 2-propyn-1-ol, a compound with a triple bond and an OH group, have been measured up to 8 GPa pressure. The liquid phase showed a phase transition around 2 GPa for a thin sample spread on KBr. The sharpening of the infrared peaks and discontinuous frequency shift indicated a transition to a crystalline phase. For a thick sample, infrared spectra showed continuous changes in peak width and frequency. The liquid transformed to an amorphous phase around 2 GPa. Polymerization occurred around 8 GPa in both the crystalline and amorphous phases. The polymerization process was a multi-step mechanism involving molecular diffusion. The diffusion step would remove the influence on the reaction of the initial molecular arrangements in the solids.

Low-temperature powder X-ray diffraction measurements have been carried out on H 2 O ice VIII in the pressure range from 5 to 50 GPa. The volume change associated with the ice VII–VIII phase transition and the compression curves of ice VIII have been obtained experimentally. The slope of the VII–VIII phase-boundary is explained qualitatively by the volume change, namely, an almost zero volume-change in a pressure-insensitive flat region below 10 GPa, and a negative volume-change in a negative slope region above 10 GPa.

Raman spectroscopy of calcium ferrite type MgAl2O4 and CaAl2O4 and heat capacity measurement of CaAl2O4 calcium ferrite were performed. The heat-capacity of CaAl2O4 calcium ferrite measured by a differential scanning calorimeter (DSC) was represented as C P(T)=190.6–1.116 × 107 T −2 + 1.491 × 109 T −3 above 250 K (T in K). The obtained Raman spectra were applied to lattice dynamics calculation of heat capacity using the Kieffer model. The calculated heat capacity for CaAl2O4 calcium ferrite showed good agreement with that by the DSC measurement. A Kieffer model calculation for MgAl2O4 calcium ferrite similar to that for CaAl2O4 calcium ferrite was made to estimate the heat capacity of the former. The heat capacity of MgAl2O4 calcium ferrite was represented as C P(T)=223.4–1352T −0.5 − 4.181 × 106 T −2 + 4.300 × 108 T −3 above 250 K. The calculation also gave approximated vibrational entropies at 298 K of calcium ferrite type MgAl2O4 and CaAl2O4 as 97.6 and 114.9 J mol−1 K−1, respectively.