Characterization of protective immune responses induced by pneumococcal surface protein A in fusion with Pneumolysin derivatives

Pneumococcal surface protein A (PspA) and Pneumolysin derivatives (Pds) are important vaccine candidates, which can confer protection in different models of pneumococcal infection. Furthermore, the combination of these two proteins was able to increase protection against pneumococcal sepsis in mice. The present study investigated the potential of hybrid proteins generated by genetic fusion of PspA fragments to Pds to increase cross-protection against fatal pneumococcal infection. Pneumolisoids were fused to the N-terminus of clade 1 or clade 2 pspA gene fragments. Mouse immunization with the fusion proteins induced high levels of antibodies against PspA and Pds, able to bind to intact pneumococci expressing a homologous PspA with the same intensity as antibodies to rPspA alone or the co-administered proteins. However, when antibody binding to pneumococci with heterologous PspAs was examined, antisera to the PspA-Pds fusion molecules showed stronger antibody binding and C3 deposition than antisera to co-administered proteins. In agreement with these results, antisera against the hybrid proteins were more effective in promoting the phagocytosis of bacteria bearing heterologous PspAs in vitro, leading to a significant reduction in the number of bacteria when compared to co-administered proteins. The respective antisera were also capable of neutralizing the lytic activity of Pneumolysin on sheep red blood cells. Finally, mice immunized with fusion proteins were protected against fatal challenge with pneumococcal strains expressing heterologous PspAs. Taken together, the results suggest that PspA-Pd fusion proteins comprise a promising vaccine strategy, able to increase the immune response mediated by cross-reactive antibodies and complement deposition to heterologous strains, and to confer protection against fatal challenge

Patient safety in nursing care during medication administration

Objetivo: evaluar la conformidad de la práctica asistencial del equipo de enfermería durante la administración de medicamentos vía catéter vascular central. Método: se trata de un estudio descriptivo, prospectivo, observacional, realizado en una Unidad de Terapia Intensiva. La muestra no probabilística, de tipo intencional, está constituida de 3402 observaciones de administraciones de medicamentos en pacientes con acceso vascular central. El instrumento de recolección, validado previamente, está construido y fundamentado en la Guía para la Prevención de Infecciones Relacionadas con el Catéter Intravascular. La colecta se llevó a cabo a partir de la observación directa de la práctica asistencial desempeñada por el equipo de enfermería. El análisis utilizó la estadística analítica, descriptiva e inferencial (Distribución de Pearson o Ji-cuadrada y el Test Exacto de Fisher). Resultados: se observaron 3.402 acciones relacionadas con la administración de medicamentos. El número mayor de acciones lo realizaron los Técnicos de Enfermería del sexo femenino. En ninguno de los procedimientos el profesional ejecutó todas las acciones necesarias, con el 0,2% de las administraciones de medicamentos antecedidas por la higienización de las manos y el 1,3%, por la desinfección de frascos multidosis, ampollas o inyectores. Conclusión: la práctica evaluada fue clasificada como indeseada. La no obtención de la conformidad anhelada ocurrió, probablemente, debido a la baja adhesión de los profesionales a la práctica de higienización de las manos y a la desinfección de materiales, inyectores y conectores.Objective: to evaluate the conformity of care practices of the nursing team during the administration of drugs through central vascular catheter. Method: a descriptive, prospective, observational study conducted in an Intensive Care Unit. The non-probabilistic intentional sample consisted of 3402 observations of drug administrations in patients with central vascular catheters. The previously validated collection instrument was constructed based on the Guideline for Prevention of Intravascular catheter-related infections. Data was collected through direct observations of nursing practices performed by the nursing team. The analysis used analytical, descriptive and inferential statistics (Chi-square test and Fisher’s exact test). Results: a total of 3402 procedures of drug administrations were observed. Female nursing technicians performed the highest number of actions. In none of the procedures did the professional perform all necessary actions. 0.2% of drug administrations were preceded by hand hygiene and 1.3% by disinfection of the multidose vial, ampoule or injectors. Conclusion: the practice evaluated was classified as undesirable. Failure to achieve the desired conformity was probably due to the low adherence of professionals to the practice of hand hygiene and disinfection of materials, injectors and connectors.Objetivo: avaliar a conformidade da prática assistencial da equipe de enfermagem durante a administração de medicamentos por cateter vascular central. Método: estudo descritivo, prospectivo, observacional, realizado em Unidade de Terapia Intensiva. A amostra não probabilística, do tipo intencional, é constituída de 3402 observações de administrações de medicamentos em pacientes em uso de acesso vascular central. O instrumento de coleta, previamente validado, é construído e alicerçado no Guideline for Prevention of Intravascular cateter-related infections. A coleta se deu a partir da observação direta da prática assistencial realizada pela equipe de enfermagem. A análise utilizou estatística analítica, descritiva e inferencial (Teste de Qui-quadrado e Exato de Fisher). Resultados: foram observadas 3402 ações relacionadas a administrações de medicamentos. O maior número de ações foi realizado por Técnicos de Enfermagem do sexo feminino. Em nenhum dos procedimentos o profissional executou todas as ações necessárias, com 0,2% das administrações de medicamento antecedidas pela higienização das mãos e 1,3% pela desinfecção do frasco multidose, ampola ou injetores. Conclusão: a prática avaliada foi classificada como indesejada. A não obtenção da conformidade almejada deu-se, provavelmente, pela baixa adesão dos profissionais à prática de higienização das mãos e à desinfecção de materiais, injetores e conectores

Sistematização de experiências de trabalho com grupos nos Centros de Referência em Obesidade/RJ

Produzido por profissionais dos Centros de Referência em Obesidade (CRO) em parceria com professores do Instituto de Nutrição da UERJ, este livro oferece um olhar interdisciplinar sobre a questão da obesidade, ampliando as possibilidades de abordagens de educação e promoção da saúde relacionadas ao excesso de peso. A publicação parte do contexto macropolítico brasileiro sobre as questões da obesidade, em relação aos dados epidemiológicos, políticas públicas e documentos e publicações norteadoras da área. Segue-se a apresentação dos Centros de Referência em Obesidade e de conceitos-chave para esse serviço, incluindo um olhar sobre as vivências, atividades e temas vitais ao cotidiano desses profissionais de saúde e daqueles que demandam os cuidados

Convalescent plasma for COVID-19 in hospitalised patients : an open-label, randomised clinical trial

Background: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. Methods: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. Results: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48–68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8–12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference −3.7%, 95% CI −18.8–11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. Conclusions: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone

A single-dose strategy for immunization with live attenuated vaccines is an effective option before treatment initiation in multiple sclerosis patients

Multiple sclerosis; Infections; VaccinationEsclerosi múltiple; Infeccions; VacunacióEsclerosis múltiple; Infecciones; VacunaciónBackground: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized. Objectives: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS. Methods: Retrospective observational study in pwMS vaccinated against VAR and/or MMR. We compared seroprotection rates and antibody geometric mean titers (GMTs) between the two strategies. Results: Ninety-six patients were included. Thirty-one patients received VAR and 67 MMR. In the SDA group, the seroprotection rate was 66.7% (95% confidence interval (CI): 53.3–78.3) versus 97.2% (95% CI: 85.5–99.9) in the SIS (p < 0.001). For the seroprotected patients, GMTs were similar for both schemes. Conclusion: An SDA of VAR and/or MMR vaccines could be sufficient to protect almost two-thirds of patients. Testing immunogenicity after a single dose of VZ and/or MMR could be included in routine clinical practice to achieve rapid immunization.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project PI19/01606 and co-funded by the European Union and ECTRIMS clinical fellowship awarded to René Carvajal from 2021 to 2022

The Susceptibility of Trypanosomatid Pathogens to PI3/mTOR Kinase Inhibitors Affords a New Opportunity for Drug Repurposing

In our study we describe the potency of established phosphoinositide-3-kinase (PI3K) and mammalian Target of Rapamycin (mTOR) kinase inhibitors against three trypanosomatid parasites: Trypanosoma brucei, T. cruzi, and Leishmania sp., which are the causative agents for African sleeping sickness, Chagas disease, and leishmaniases, respectively. We noted that these parasites and humans express similar kinase enzymes. Since these similar human targets have been pursued by the drug industry for many years in the discovery of cellular growth and proliferation inhibitors, compounds developed as human anti-cancer agents should also have effect on inhibiting growth and proliferation of the parasites. With that in mind, we selected eight established PI3K and mTOR inhibitors for profiling against these pathogens. Among these inhibitors is an advanced clinical candidate against cancer, NVP-BEZ235, which we demonstrate to be a highly potent trypanocide in parasite cultures, and in a mouse model of T. brucei infection. Additionally, we describe observations of these inhibitors' effects on parasite growth and other cellular characteristics

Nascidos vivos com fenda palatina e labial: estudo epidemiológico

Introduction: Cleft lip and palate is a congenital malformation resulting from the inadequate fusion of bony structures during embryonic development. The etiology is multifactorial, involving genetic and environmental factors. Methodology: This study constitutes a descriptive epidemiological analysis focusing on the investigation of cases of live births with cleft lip and palate in Brazil. Data collection will be conducted through the Live Birth Information System (SINASC) during the period from 2017 to 2021. Results: The gender distribution of live births with cleft lip and palate indicates a male predominance in the sample, representing approximately 58.49% (n=4,390) of the total. Meanwhile, the percentage of female individuals is approximately 41.01% (n=3,078). The category "Unknown" has a very small representation, accounting for only 0.51% (n=38) of the sample. Conclusion: It is observed that live births with cleft lip and palate should not be overlooked. There is a significant number of cases each year, necessitating further related studies to provide solutions in society that directly benefit those affected.Introdução: A fenda labial e palatina é uma malformação congênita resultante da não fusão das estruturas ósseas adequadas durante o desenvolvimento embrionário. A etiologia é multifatorial, envolvendo fatores genéticos e ambientais. Metodologia: Este estudo constitui uma análise epidemiológica descritiva com enfoque na investigação dos casos de nascidos vivos com fenda labial e palatina no Brasil. A coleta de dados será realizada por meio do Sistema de Informações sobre Nascidos Vivos (SINASC) durante o período de 2017 a 2021. Resultado: A distribuição de gênero dos nascidos vivos com fenda labial e palatina indica que há uma maioria masculina na amostra, representando cerca de 58,49% &nbsp;(n= 4.390) do total. Enquanto isso, a porcentagem de pessoas do sexo feminino é de aproximadamente 41,01% (n = 3.078) A categoria "Ignorado" tem uma representação muito pequena, com apenas 0,51% (n = 38) da amostra. Conclusão: Observa-se que os nascidos vivos com fenda labial e palatina não devem ser negligenciados. Há uma quantidade significativa de nascidos por ano, sendo indispensável mais estudos relacionados, a fim de trazer soluções na sociedade que beneficiem diretamente os acometidos