Fulminant hepatitis: a clinical review of 11 years

24 cases of fulminant hepatitis (FH) hospitalized in the Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the period from January 1976 to December 1986 were reviewed from their clinical, epidemiological and laboratorial aspects. 88% of the patients died; 20 patients (83%) presented hemorrhages and, of these, 19 died. Bacterial infections occurred in 14 patients (58%) all of whom died. Ascitis was noted in 3 cases; cerebral edema was present in 16 cases. Maximal ALT levels for each patient during hospitalization ranged widely from 81 to 4,460 UI/l. Thirteen patients presented high creatinine levels (54%). Prothrombin time activity ranged from 2.1% to 67%. Fever was present in 20 cases (83%). Encephalopathy occurred within the first 2 weeks of illness in 72% of the cases. In 7 cases other illnesses were present. The etiology could not be determined in 13 cases. In 3 cases it was due to yellow fever and 6 cases were caused by viruses other than yellow fever. In one case the cause was drug usage and in another case, possibly alcohol. The authors believe that the clinical definition of FH requires further discussion before it is established. In this study FH is a young person's disease. The mortality found was similar to that by other authors. Factors that contributed to death were: hemorrhages and bacterial infection. Factors that worsened the prognosis of hepatitis were: associated illnesses and surgical procedure. The levels of ALT during hospitalization did not correlate well with the severity of the hepatitis. The authors believe that yellow fever should be considered a cause of FH where the clinical picture meets the criteria for such, although its mechanisms of encephalopathy remain obscure. The clinical details of the 3 cases of yellow fever are presented.Vinte e quatro casos de hepatite fulminante (HF), internados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo durante o período de janeiro de 1976 a dezembro de 1986, foram revistos para a obtenção de dados clínicos, epidemiológicos e laboratoriais. 88% dos pacientes morreram. Vinte (83%) dos pacientes apresentaram hemorragias, dentre os quais 19 morreram (95%). Infecções bacterianas secundárias ocorreram em 14 pacientes (58%) todos os quais faleceram. Ascite foi notada em 3 casos e edema cerebral em 16 casos. Os valores máximos de ALT obtidos para cada paciente durante a internação variaram de 81 a 4.460 UI/l. Treze pacientes tiveram elevação de creatinina (54%). A atividade do tempo de protrombina variou de 2,1% a 67%. A febre esteve presente em 20 casos (83%). A encefalopatia surgiu durante as 2 primeiras semanas de doenças em 72% dos casos. Em 7 casos havia doenças associadas à hepatite. A etiologia não pode ser determinada em 13 casos; 3 casos foram por febre amarela; e 6 casos por outros vírus. Em 1 caso a causa foi drogas e em um caso, possivelmente, foi álcool. Os autores acreditam que a definição de HF merece discussão antes de ser totalmente aceita. Neste estudo, a HF foi uma doença que acometeu principalmente jovens. A letalidade encontrada foi semelhante a de outros estudos. Fatores que contribuíram para o óbito foram hemorragias e infecções bacterianas secundárias. Fatores de piora do prognóstico da hepatite foram a presença de outras doenças associadas e de procedimento cirúrgico. Os níveis de ALT durante a internação não refletiram a gravidade da hepatite. Os autores acreditam que a febre amarela deve ser considerada um agente etiológico de HF quando o seu quadro clínico seja compatível com tal, embora os mecanismos fisiopatológicos da encefalopatia sejam ainda obscuros. Os dados clínicos dos 3 casos de febre amarela são apresentados à parte

PONDERAÇÕES SOBRE A RELEVÂNCIA DO DESENVOLVIMENTO CIENTÍFICO PARA A PROMOÇÃO DOS DIREITOS DA PESSOA HUMANA

Na atualidade, tem se assistido à disseminação de fake news e do pensamento contrário à ciência. Em tempos pandêmicos, essa é uma temática que tem ganhado bastante destaque, especialmente ante ao fortalecimento de movimentos negacionistas e que desacreditam os avanços científicos a partir do emprego de informações que carecem de fundamentação adequada. Logo, em meio a esse cenário, o presente artigo procura trazer à tona a importância da ciência, de modo a esboçar correlações entre os avanços científicos e a promoção da dignidade da pessoa humana —      principalmente as garantias relacionadas com a segunda e terceiras dimensões de direitos fundamentais. Tomando como ponto de partida uma metodologia que se propõe a empregar o histórico e a evolução dos direitos fundamentais como fio condutor da argumentação delineada, também visa trazer um breve debate sobre uma possível quarta dimensão de direitos fundamentais ligados à biomedicina — sem, contudo, ter a pretensão de esgotar um assunto de tamanha complexidade. Em apertada síntese, procura reagir ao crescimento do pensamento contrário à ciência, empregando a metodologia científica para reafirmar a importância dos avanços tecnológicos — especialmente como mecanismo para promoção dos direitos humanos, favorecendo o efetivo exercício dos direitos fundamentais para uma parcela maior da população e colaborando para a melhora da qualidade dessa fruição. Além disso, também reitera a importância da adoção do pensamento crítico pela sociedade brasileira de forma a combater posicionamentos disruptivos e contrários à ciência

Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage

DNA vaccination elicits humoral and cellular immune responses and has been shown to confer protection against several viral, bacterial, and parasitic pathogens. Here we report that optimized codon usage of an injected DNA sequence considerably increases both humoral and cellular immune responses. We recently generated a synthetic human immunodeficiency virus type 1 gp120 sequence in which most wild-type codons were replaced with codons from highly expressed human genes (syngp120). In vitro expression of syngp120 is considerably increased in comparison to that of the respective wild-type sequence. In BALB/c mice, DNA immunization with syngp120 resulted in significantly increased antibody titers and cytotoxic T-lymphocyte reactivity, suggesting a direct correlation between expression levels and the immune response. Moreover, syngp120 is characterized by rev-independent expression and a low risk of recombination with viral sequences. Thus, synthetic genes with optimized codon usage represent a novel strategy to increase the efficacy and safety of DNA vaccination

Yersinia pestis Endowed with Increased Cytotoxicity Is Avirulent in a Bubonic Plague Model and Induces Rapid Protection against Pneumonic Plague

An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica O∶8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 107-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD50 of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the virulence strategies of Y. pestis in nature

Contrasting Deep Learning Models for Direct Respiratory Insufficiency Detection Versus Blood Oxygen Saturation Estimation

We contrast high effectiveness of state of the art deep learning architectures designed for general audio classification tasks, refined for respiratory insufficiency (RI) detection and blood oxygen saturation (SpO$_2$) estimation and classification through automated audio analysis. Recently, multiple deep learning architectures have been proposed to detect RI in COVID patients through audio analysis, achieving accuracy above 95% and F1-score above 0.93. RI is a condition associated with low SpO$_2$ levels, commonly defined as the threshold SpO$_2$ <92%. While SpO$_2$ serves as a crucial determinant of RI, a medical doctor's diagnosis typically relies on multiple factors. These include respiratory frequency, heart rate, SpO$_2$ levels, among others. Here we study pretrained audio neural networks (CNN6, CNN10 and CNN14) and the Masked Autoencoder (Audio-MAE) for RI detection, where these models achieve near perfect accuracy, surpassing previous results. Yet, for the regression task of estimating SpO$_2$ levels, the models achieve root mean square error values exceeding the accepted clinical range of 3.5% for finger oximeters. Additionally, Pearson correlation coefficients fail to surpass 0.3. As deep learning models perform better in classification than regression, we transform SpO$_2$-regression into a SpO$_2$-threshold binary classification problem, with a threshold of 92%. However, this task still yields an F1-score below 0.65. Thus, audio analysis offers valuable insights into a patient's RI status, but does not provide accurate information about actual SpO$_2$ levels, indicating a separation of domains in which voice and speech biomarkers may and may not be useful in medical diagnostics under current technologies.Comment: 23 pages, 4 figures, in review at Journal of Biomedical Signal Processing and Contro

Discriminant audio properties in deep learning based respiratory insufficiency detection in Brazilian Portuguese

This work investigates Artificial Intelligence (AI) systems that detect respiratory insufficiency (RI) by analyzing speech audios, thus treating speech as a RI biomarker. Previous works collected RI data (P1) from COVID-19 patients during the first phase of the pandemic and trained modern AI models, such as CNNs and Transformers, which achieved $96.5\%$ accuracy, showing the feasibility of RI detection via AI. Here, we collect RI patient data (P2) with several causes besides COVID-19, aiming at extending AI-based RI detection. We also collected control data from hospital patients without RI. We show that the considered models, when trained on P1, do not generalize to P2, indicating that COVID-19 RI has features that may not be found in all RI types.Comment: 5 pages, 2 figures, 1 table. Published in Artificial Intelligence in Medicine (AIME) 202

Indicadores de desempenho sobre uso de antibioticoprofilaxia cirúrgica: construção e validação

The study aims to contribute to hospital infection control practices by the development and validation of performance indicators to evaluate the use of surgical antibiotic prophylaxis. Using a methodology for drawing up measures to evaluate health practices, one basic and five secondary indicators were constructed and submitted to content validation through attributes of operational manual, representativeness and applicability by technical consensus of specialists. All indicators got consensus, although one attribute of applicability of the basic indicator and the secondary indicators were questioned by the specialists. The suggestions of the experts, however, allowed adjustments and therefore validation. Given that different types of evaluation of clinical practices have been built, but not always substantiated and validated, it is believed that methods of construction and validation like in this study are its greatest contribution.O estudo pretende contribuir com práticas de controle de infecção hospitalar, pela elaboração e validação de indicadores de avaliação de desempenho do uso de antibioticoprofilaxia cirúrgica. Por meio de metodologia de elaboração de medidas de avaliação em saúde, foram construídos um indicador básico e cinco secundários, submetidos à validação de construto operacional, representatividade e aplicabilidade, por meio de técnica de consenso de especialistas. Todos os indicadores obtiveram consenso nos atributos dos construtos operacionais e de representatividade. Quanto à aplicabilidade, o indicador básico não obteve consenso somente para o atributo de acessibilidade, e os secundários para o de contextualização. As sugestões dos especialistas, contudo, permitiram ajustes e, portanto, validação. Tendo em vista que diversos tipos de avaliação de práticas assistenciais têm sido construídos,  embora nem sempre sejam fundamentados e validados, acreditase que os modos de construção e validação utilizados neste estudo constituem a sua maior contribuição