82 research outputs found
Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?
Responsible for up to 30,000 deaths annually, leishmaniasis is a complex spectrum of diseases endemic in 97 countries around the globe. Disease control relies heavily on the early diagnosis and treatment of the active cases (relevant for anthroponotic disease), although it is widely accepted that a prophylactic vaccine for human leishmaniasis is the way to achieve the successful elimination of human disease (taking in consideration the vast list of non-human reservoirs that enable the perpetuation of parasites all around the globe). The notion that infection leads to strong and long-lasting immunity against leishmaniasis supports vaccination as an achievable goal. However, and in spite of the different candidates tested along the years, till date, we still do not have an approved vaccine for humans. In this chapter, we will explore the last advances made in the field of vaccines against Leishmania without forgetting the historical perspective, essential to the understanding of the road already undergone. We will then discuss the correlates of disease and protection, still neither consensual nor definitive, as well as the issue of pre-clinical to clinical translation. The complete understanding of these issues will be essential for the approval of a successful vaccine for human leishmaniasis
Adenovírus isolados de civis e militares da cidade do Rio de Janeiro, Brasil
Adenovirus are important pathogen primarily associated to respiratory infections of children and military personnel, even though it is also associated to cases of conjunctivitis and keratoconjunctivitis. We analyzed respiratory secretion collected from subjects with and without respiratory infection symptoms, being 181 civilians and 221 military subjects. The samples were inoculated in HEp-2 and/or A549 tissue cultures for viral isolation. Samples presenting cytopathogenic effect (CPE) in any tissue culture were tested by a polymerase chain reaction (PCR) assay to confirm adenovirus isolation. The isolates confirmed as adenovirus were further analyzed by restriction endonuclease assay for determination of viral species. Three isolates were identified as specie A (two from civilian and one from military), one isolate from military was identified as specie C, and one isolate from civilian was identified as specie D. For two isolates the specie could not be identified.Os adenovírus são importantes patógenos associados em geral, a infecções respiratórias em crianças e militares, embora, também estejam associados a surtos de conjuntivite e ceratoconjuntivite epidêmica. Neste estudo, foram analisadas 402 amostras de secreção respiratória colhidas de indivíduos com e sem sintomas de infecção respiratória, sendo 181 de civis e 221 de militares. As amostras foram inoculadas em cultura de células HEp-2 e/ou A549 para o isolamento viral; aquelas que apresentaram efeito citopatogênico (CPE) em alguma das culturas de células foram submetidas a reação da polimerase em cadeia (PCR) para confirmar o isolamento de adenovírus. Os isolados confirmados como sendo adenovírus foram posteriormente submetidos a digestão com endonucleases de restrição para a identificação da espécie viral. Três isolados foram identificados como espécie A (sendo dois isolados de civis e um de militar), um isolado de militar foi identificado como espécie C, e um isolado de civil foi identificado como espécie D. Para dois isolados a espécie não pode ser identificada
Genotipagem de Papiloma Vírus Humano em paciente com papilomatose laríngea recorrente
Os HPVs são vírus de DNA circular de fita dupla medindo cerca de 8000pb. Vários estudos têm demonstrado que o HPV é o agente causal de tumores benignos, como papilomas, verrugas comuns e condilomas. Com o avanço das técnicas de detecção molecular, o genoma do HPV tem sido freqüentemente identificado em células neoplásicas malignas de origem epitelial, passando-se a associar o HPV a alguns tumores epiteliais, principalmente ao carcinoma cervical. Recentemente, diversas pesquisas se concentraram na tentativa de associar a infecção por HPVs aos cânceres de cabeça e pescoço. O presente relato de caso consiste na avaliação de uma paciente com história de papilomatose recorrente na laringe. Uma criança com sete anos de idade, do sexo feminino, foi atendida há dois anos com queixas de desconforto na garganta e disfonia. Os vários procedimentos clínicos indicaram presença de papilomas na laringe e o histopatológico acusou presença de coilocitose, achado sugestivo da infecção por HPV. Assim, a paciente foi submetida à retirada cirúrgica dos papilomas. Das peças cirúrgicas foi obtido DNA total, usado na investigação molecular, por PCR, para detecção do genoma de HPV. Desta forma, foi confirmada a presença do HPV do tipo 11, corroborando os achados de outros autores que argumentam que a ocorrência latente do HPV11 tem participação na evolução dessa patologia em crianças
Avaliação da natureza da atividade catalítica de compostos de bismuto em reações de metanólise do óleo de soja
Sodium bismuthate dihydrate and two species derived from its thermal treatment were investigated as catalysts for soybean oil methanolysis and, regardless of the type of solid used, ester yields always above 76 wt% were obtained. After a single reaction course, both liquid and solid phases were characterized using several analytical methods such as X-ray diffraction and thermogravimetric analysis. As a result, the catalytic phenomenon was shown to be solely due to the leaching of alkalinecatalytic species from the solid materials
The landscape of lncRNAs in gastric cancer: from molecular mechanisms to potential clinical applications
Gastric cancer (GC) is a highly prevalent and deadly malignant neoplasm worldwide. Currently, long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators implicated in GC development and progression. Dysregulated expression of lncRNAs is commonly associated with enhanced tumor migration, invasiveness, and therapy resistance, highlighting their potential as promising targets for clinical applications. This review offers a comprehensive historical overview of lncRNAs in GC, describes the molecular mechanisms, and discusses the prospects and challenges of establishing lncRNAs as precision biomarkers
Protective efficacy in a hamster model of a multivalent vaccine for human visceral leishmaniasis (Mulevaclin) consisting of the kmp11, leish-f3+, and ljl143 antigens in virosomes, plus gla-se adjuvant
Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if untreated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the Leishmania membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the parasite proteins nucleoside hydrolase, sterol-24-c-methyltransferase, and cysteine protease B), and the sand fly salivary protein LJL143, in two dose ratios. The inclusion of the TLR4 agonist GLA-SE as an adjuvant, and the use of virosomes (VS) as a delivery system, are also examined. In a hamster model of VL, the vaccine elicited antigen-specific immune responses prior to infection with Leishmania infantum. Of note, the responses were greater when higher doses of KMP11 and LEISH-F3+ proteins were administered along with the GLA-SE adjuvant and/or when delivered within VS. Remarkably, hamsters immunized with the complete combination (i.e., all antigens in VS + GLA-SE) showed significantly lower parasite burdens in the spleen compared to those in control animals. This protection was underpinned by a more intense, specific humoral response against the KMP11, LEISH-F3+, and LJL143 antigens in vaccinated animals, but a significantly less intense antibody response to the pool of soluble Leishmania antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against L. infantum infection, supporting the advancement of the vaccine formulation into process development and manufacturing and the conduction of toxicity studies towards future phase I human clinical trialsEuropean Community’s Seventh Framework Programme, grant number 603181 (Clinical Studies on a Multivalent Vaccine for Human Visceral Leishmaniasis [MuLeVaClin]), and by the RD16CIII/0003/0002 and RD16/0027/0008 Red de Investigación Cooperativa de Enfermedades Tropicales, Subprograma RETICS del Plan Estatal de I+D+I 2013–2016, co-funded by ERD
Protective Efficacy in a Hamster Model of a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin) Consisting of the KMP11, LEISH-F3+, and LJL143 Antigens in Virosomes, Plus GLA-SE Adjuvant
Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if untreated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the Leishmania membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the parasite proteins nucleoside hydrolase, sterol-24-c-methyltransferase, and cysteine protease B), and the sand fly salivary protein LJL143, in two dose ratios. The inclusion of the TLR4 agonist GLA-SE as an adjuvant, and the use of virosomes (VS) as a delivery system, are also examined. In a hamster model of VL, the vaccine elicited antigen-specific immune responses prior to infection with Leishmania infantum. Of note, the responses were greater when higher doses of KMP11 and LEISH-F3+ proteins were administered along with the GLA-SE adjuvant and/or when delivered within VS. Remarkably, hamsters immunized with the complete combination (i.e., all antigens in VS + GLA-SE) showed significantly lower parasite burdens in the spleen compared to those in control animals. This protection was underpinned by a more intense, specific humoral response against the KMP11, LEISH-F3+, and LJL143 antigens in vaccinated animals, but a significantly less intense antibody response to the pool of soluble Leishmania antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against L. infantum infection, supporting the advancement of the vaccine formulation into process development and manufacturing and the conduction of toxicity studies towards future phase I human clinical trials.This research was funded by the European Community’s Seventh Framework Programme, grant number 603181 (Clinical Studies on a Multivalent Vaccine for Human Visceral Leishmaniasis [MuLeVaClin]), and by the RD16CIII/0003/0002 and RD16/0027/0008 Red de Investigación Cooperativa de Enfermedades Tropicales, Subprograma RETICS del Plan Estatal de I+D+I 2013–2016, co-funded by ERDF “Una manera de hacer Europa” funds.S
O professor e o aluno do ensino fundamental em sala de aula: indisciplina ou indícios de TDAH? / The teacher and student in classroom education: indiscipline or ADHD?
Este artigo é desenvolvido no contexto da psicopegadogia, e tem como objetivo “propor uma sistemática para os professores de Ensino Fundamental a distinguirem comportamentos de indisciplina de índicos de TDAH de seus alunos em sala de aula (crianças de 7 a 12 anos incompletos)”. O estudo é desenvolvido como uma pesquisa explicativa/analítica, bibliográfica e qualitativa, valendo-se da coleta de dados em fontes ecundárias (artigos, livros, trabalhos científicos). Tem como base principal as obras de Garcia (1999), Freller (2001), Estrela (1992), Vasconcellos (1994), Benczik e Rohde (1999), Topczewski (1999) e Diniz Neto e Sena (2007), dentre outras, as quais levam a argumentações e conclusões pelo método dedutivo. Justifica-se sua elaboração por responder uma questão polêmica na atualidade: “Como o professor de Ensino Fundamental pode distinguir os comportamentos de indisciplina ou indícios de TDAH em sala de aula? Tem como resposta cinco passos de ações, em um crescente de conhecimentos. Os quatros primeiros dirigem-se a conhecer personalizadamente o aluno a julgar, se auto conhecer didática-profissionalmente, saber o que é a indisciplina do aluno em sala de aula, o que é o TDAH, e quais os comportamentos característicos do estágio cognitivo das operações concretas. E o quinto faz a distinção entre os comportamentos das crianças. Conclui-se que: (a) Aluno de comportamento normal (tem comportamento esperado junto à turma; quebra regras e preceitos apenas quando motivado pelo professor; e não tem indícios de TDAH). (b) Aluno de comportamento indisciplinado (quebra regras e preceitos do professor ou da escola sem motivação do professor; e não tem indícios de TDAH). (c) Aluno com indícios de TDAH (Quebra regras e preceitos do professor ou da escola sem motivação do professor e tem indícios de TDAH)
Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial
Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt
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