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Impact of early life geohelminths on wheeze, asthma and atopy in ecuadorian children at 8 years
Wellcome Trust, Grant/Award Number: 088862/Z/09/ZBackground: Early-life exposures to geohelminths may protect against development of wheeze/asthma and atopy. Objective: To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years. Methods: Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. Results: 1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086)
Neotropical primate models for malaria research: 25 years of collaboration between Laboratory of Malaria Research (IOC, Fiocruz) and Centro Nacional de Primatas (IEC, SVS)
A malária continua sendo um dos principais problemas globais de saúde pública, sendo responsável pela morte de
409.000 pessoas anualmente, principalmente devido à infecção por Plasmodium falciparum. Assim, o desenvolvimento
de uma vacina tem sido uma das prioridades de pesquisa para o enfrentamento desse problema. Não existe vacina
licenciada contra a malária e, embora mais de 30 antígenos tenham sido identificados como candidatos vacinais,
nenhum deles gerou uma perspectiva sólida de que uma vacina possa estar disponível nos próximos anos. Torna-se
fundamental a pesquisa de candidatos vacinais mais imunogênicos, eficazes e seguros. Os primatas neotropicais dos
gêneros Saimiri e Aotus são os modelos recomendados para estudos experimentais em malária, visto que podem ser
infectados por plasmódios humanos. O Laboratório de Pesquisa em Malária (LabMal) da Fundação Oswaldo Cruz
estuda os mecanismos de defesa e doença na malária e utiliza os modelos Saimiri e Aotus para a avaliação pré-clínica
de antígenos candidatos à vacina e estudos de mecanismos de aquisição de imunidade e fisiopatogenia da malária.
Para a realização dos estudos, o LabMal estabeleceu uma parceria com o Centro Nacional de Primatas (CENP) do
Instituto Evandro Chagas, que resultou na ampliação das colônias de Saimiri sciureus, colocando o CENP entre as raras
instituições no mundo que dispõem desse recurso para pesquisa. O presente trabalho é um retrospecto dos resultados
obtidos durante 25 anos de parceria entre o LabMal e o CENP na utilização de primatas Saimiri e Aotus como modelos
de estudo para pesquisa e desenvolvimento de uma vacina antimalárica.Malaria remains a significant public health problem and, responsible for 409,000 deaths annually, mainly due to infection
by Plasmodium falciparum. Thus, the development of an effective vaccine has been a research priority to address the
problem. There is no licensed vaccine, and although more than 30 antigens have been identified as candidates, none
of them has yet generated a solid prospect that an effective vaccine may be available in the coming years. Therefore,
it is essential to search for new, more immunogenic, more effective and safer vaccine candidates. The neotropical,
non-human primates (NHP) of the genera Saimiri and Aotus are recommended as experimental models for the study of
human malaria because these animals can be infected with the Plasmodium that infect humans. The Laboratory of Malaria
Research (LabMal, Fiocruz) studies the mechanisms of defense and disease in malaria and uses the Saimiri and Aotus
experimental models for preclinical evaluation of antimalarial vaccine candidates and for conducting studies of immunity
acquisition mechanisms and physiopathogenesis of malaria. To carry out the studies, LabMal established a partnership
with the Centro Nacional de Primatas (CENP) of the Instituto Evandro Chagas, which resulted in the expansion of Saimiri
sciureus colonies, placing CENP among the few institutions in the world that have this resource for malaria research. The
present paper is a retrospective of the results obtained during 25 years of partnership between LabMal and CENP in the
use of Saimiri and Aotus as study models for research and development of an antimalarial vaccine
Reproductive justice and the Zika epidemic in Brazil: urgent ethical issues in public health emergencies
O argumento central desta tese é que o patriarcado operou para desviar o foco daquelas mais afetadas pela epidemia de Zika \2013 mulheres e meninas em idade reprodutiva. E, desse modo, aprofundando vulnerabilidades preexistentes que se ancoram na desigualdade de gênero. Esta tese se baseia na compreensão do gênero como um regime político onde o patriarcado atua para manter as desigualdades sob a justificativa de que haveria uma hierarquia de gênero. Esta é uma pesquisa que utiliza-se de lentes feministas para uma análise bioética sobre como as assimetrias de gênero têm efeitos para a vida de mulheres, meninas e comunidade. A doença transmitida pelo vírus zika era pouco conhecida até 2015. Em razão de suas consequências para mulheres grávidas e fetos \2013 especialmente meninas e mulheres vivendo no nordeste do Brasil, em 2016 a Organização Mundial da Saúde declarou Emergência de Saúde Pública de Interesse Internacional. Atualmente sabe-se que o vírus Zika causa a síndrome congênita do Zika, como consequência da infecção congênita devido à transmissão do vírus da mulher grávida para o feto. Além disso, também é sabido que o vírus é transmitido sexualmente. Zika acabou sendo o primeiro arbovírus conhecido a ter consequências sexuais e reprodutivas. Esta tese é composta por três artigos científicos e um editorial que apresenta resultados de estudos que investigam os efeitos da epidemia de zika nas vidas de mulheres. Argumentamos que a desigualdade de gênero contribuiu para os efeitos encontrados a seguir: 1- a epidemia de Zika piorou as vulnerabilidades sociais e econômicas de mulheres e meninas afetadas; 2- o surto de zika em um contexto em que há uma inadequação das respostas para garantia de saúde sexual e reprodutiva, contribuiu para uma maior vulnerabilização da vida de mulheres e meninas; a3- a assimetria de gênero e suas dinâmicas de poder impactaram a participação das mulheres em pesquisas e agravaram suas vulnerabilidades. O patriarcado impôs um apagamento do discurso público no tema da saúde e direitos sexuais e reprodutivos, incluindo o direito ao aborto. Este impedimento do discurso público no contexto de uma emergência de saúde pública devido a um vírus, cujo principal impacto é na saúde reprodutiva, tirou o foco daquelas que correm mais risco e são afetadas por ele: mulheres e meninas. Nesse sentido, a epidemia de Zika foi um estudo de caso sem precedentes que reforça que os direitos sexuais e reprodutivos, incluindo o direito ao aborto, devem ser uma questão central para justiça reprodutiva e igualdade de gênero em qualquer resposta a emergências de saúde pública.The central argument of this dissertation is that patriarchy operated to shift the focus away from those most affected by the Zika epidemic \2013 women and girls of reproductive age \2013 reifying vulnerabilities based on gender inequality. This dissertation is based on the understanding of gender as a political regimen where patriarchy acts to maintain gender inequalities based on the assumption of gender hierarchy. As such, this is a feminist approach to research and bioethical analysis where the examination of social inequality focuses on the evaluation of the effects of gender asymmetries in the individual and within the community. Zika virus is a mosquito-borne disease that was mostly unknown until the World Health Organization decelerated it a Public Health Emergency of International Concern in 2016 due to the effects of the Zika virus in the pregnancy and fetal development observed in women and girls living in the northeast region of Brazil. Zika virus was found to cause congenital Zika syndrome, as a consequence of the congenital infection due to the transmission of the virus from the pregnant women to the fetus. It was also found be sexually transmitted. Zika turned out to be the first known arbovirus to have sexual and reproductive consequences. This dissertation is composed of three scientific articles and an editorial piece that present research findings done by investigating the effects of Zika on the lives of women directly impacted by the Zika epidemic. The following main aspects of gender inequality were revealed: 1- the Zika epidemic worsened the social and economic vulnerabilities of affected women and girls; 2- the Zika outbreak in the context of inadequate sexual and reproductive health rendered women and girls even more vulnerable; a3- gender asymmetry and power structure dynamics impacted women\2019s research participation and aggravated their vulnerabilities. Patriarchy imposed an absence of public discourse regarding sexual and reproductive health and rights, including the right to abortion. This impediment of public discourse in the context of a public health emergency due to a virus whose major impact is on reproductive health shifted the focus away from those most at risk of and affected by it: women and girls. In this sense, the Zika epidemic was an unprecedented case study that reifies that sexual and reproductive rights, including the right to abortion, must be a central issue in any public health emergency responses as a matter of reproductive justice and gender equality
Uso de Plantas Medicinales por mujeres embarazadas em uma Unidad Básica de Salud de Juazeiro do Norte - CE
Introdução: No período gestacional o corpo materno sofre inúmeras alterações fisiológicas em um curto espaço de tempo. O uso de produtos farmacoterapêuticos na gestação deve ser cauteloso já que muitas substâncias encontradas nesses produtos podem trazer riscos gravíssimos para a gestante. Objetivo: Avaliar o uso de plantas medicinais por gestantes atendidas em uma unidade básica de saúde de Juazeiro do Norte-CE. Método: O presente estudo é caracterizado como transversal e observacional de caráter quantitativo. Realizado com 15 gestantes de uma UBS de juazeiro do norte no período de outubro de 2019 a novembro de 2019. Resultados: No presente estudo foi avaliado o uso de produtos farmacoterapêuticos por gestantes atendidas em uma Unidade Básica de Saúde de Juazeiro do Norte, de início caracterizou-se o perfil socioeconômico, em seguida o histórico gestacional, e por fim verificou-se o uso de plantas medicinais pelas gestantes, onde notou-se que 20% das gestantes utilizavam algum tipo de planta medicinal. Conclusão: Foi possível observar as plantas medicinais utilizadas pelas gestantes em uma Unidade Básica de Saúde de juazeiro do Norte-CE, podendo verificar que mesmo sendo realizada pela minoria das gestantes a prática de uso de produtos farmacoterapêuticos continua em alta atualmente. Desse modo, é de extrema importância que as mulheres em estado gestacional tenham o devido cuidado com a sua saúde quando se trata do uso de plantas medicinais, pois muitas das plantas medicinais não possuem estudos que indiquem sua eficácia e segurança, assim como os seus efeitos tóxicos.Introduction: In the gestational period, the maternal body undergoes numerous physiological changes in a short period of time. The use of pharmacotherapeutic products during pregnancy should be cautious since many substances found in these products can bring very serious risks to the pregnant woman. Objective: To evaluate the use of medicinal plants by pregnant women attended at a basic health unit in Juazeiro do Norte-CE. Method: The present study is characterized as cross-sectional and observational with a quantitative character. Conducted with 15 pregnant women from a UBS in Juazeiro do Norte from October 2019 to November 2019. Results: In the present study, the use of pharmacotherapeutic products by pregnant women attended at a Basic Health Unit in Juazeiro do Norte, was evaluated. the socioeconomic profile was characterized, followed by the gestational history, and finally, the use of medicinal plants by pregnant women was verified, where it was noted that 20% of pregnant women used some type of medicinal plant. Conclusion: It was possible to observe the medicinal plants used by pregnant women in a Basic Health Unit in juazeiro do Norte-CE, and it can be seen that even though it is performed by a minority of pregnant women, the practice of using pharmacotherapeutic products remains on the rise today. Thus, it is extremely important that women in gestational status take due care of their health when it comes to the use of medicinal plants, as many medicinal plants do not have studies that indicate their efficacy and safety, as well as their effects toxic.Introducción: En el período gestacional, el cuerpo materno sufre numerosos cambios fisiológicos en un corto período de tiempo. El uso de productos farmacoterapéuticos durante el embarazo debe ser cauteloso ya que muchas sustancias que se encuentran en estos productos pueden traer riesgos muy serios para la mujer embarazada. Objetivo: Evaluar el uso de plantas medicinales por parte de gestantes atendidas en una unidad básica de salud en Juazeiro do Norte-CE. Método: El presente estudio se caracteriza por ser de corte transversal y observacional con carácter cuantitativo. Realizado con 15 gestantes de una UBS de Juazeiro do Norte de octubre de 2019 a noviembre de 2019. Resultados: En el presente estudio se evaluó el uso de productos farmacoterapéuticos por parte de gestantes atendidas en una Unidad Básica de Salud de Juazeiro do Norte, iniciando el análisis socioeconómico. se caracterizó el perfil, seguido de la historia gestacional, y finalmente se verificó el uso de plantas medicinales por parte de gestantes, donde se constató que el 20% de las gestantes usaba algún tipo de planta medicinal. Conclusión: se pudo observar las plantas medicinales utilizadas por gestantes en una Unidad Básica de Salud en juazeiro do Norte-CE, y se puede observar que si bien la práctica de uso de productos farmacoterapéuticos aún es alta, la práctica de uso de productos farmacoterapéuticos sigue siendo alto hoy. Por ello, es de suma importancia que las mujeres en estado gestacional cuiden debidamente su salud cuando se trata del uso de plantas medicinales, ya que muchas plantas medicinales no cuentan con estudios que indiquen su eficacia y seguridad, así como sus efectos tóxicos
Synthesis of Eudragit® L100-coated chitosan-based nanoparticles for oral enoxaparin delivery
Enoxaparin is an effective biological molecule for prevention and treatment of coagulation disorders. However, it is poorly absorbed in the gastrointestinal tract. In this study, we developed an Eudragit® L100 coated chitosan core shell nanoparticles for enoxaparin oral delivery (Eud/CS/Enox NPs) through a completely eco-friendly method without employing any high-energy homogenizer technique and any organic solvents. Spherical nanocarriers were successfully prepared with particle size lower than 300 nm, polydispersity index about 0.12 and zeta potential higher than +25 mV, entrapment efficiency greater than 95% and the in vitro release behavior confirms the good colloidal stability and the successful Eudragit® L100 coating process demonstrated by negligible cumulative enoxaparin release (<10%) when the particles are submitted to simulated gastric fluid conditions. Finally, we demonstrated that the core-shell structure of the particle influenced the drug release mechanism of the formulations, indicating the presence of the Eudragit® L100 on the surface of the particles. These results suggested that enteric-coating approach and drug delivery nanotechnology can be successfully explored as potential tools for oral delivery of enoxaparin
A new biocompatible silver/polypyrrole composite with in vitro antitumor activity
We used an in situ chemical oxidation method to prepare a new composite of silver nanoparticles (AgNPs) with polypyrrole (PPy), whose properties were optimized through a 23-factorial design of the synthesis conditions. The successful formation of the AgNPs/PPy composite was confirmed by UV-Visible and FTIR spectroscopies. Transmission electron microscopy revealed the presence of AgNPs smaller than 100 nm, dispersed into the PPy matrix. This hybrid composite exhibits a blue fluorescence emission after excitation in the ultraviolet region. In MTT assays, the AgNPs/PPy composite exhibited low cytotoxicity toward non-tumoral cell lines (fibroblast, Vero, and macrophages) and selectively inhibited the viability of HeLa cells. The AgNPs/PPy composite induces ultrastructural changes in HeLa cells that are consistent with the noticeable selectivity exhibited toward them when compared to its action against non-tumoral cell lineages. Also, the AgNPs/PPy exhibited a hemolytic activity below 14% for all blood groups tested, at concentrations up to 125 μg/mL. These results suggest that the AgNPs/PPy composite has a promising potential for use as an antitumoral agent
Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection?
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.O coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2) induz uma síndrome respiratória aguda grave chamada COVID-19. As manifestações clínicas do COVID-19 incluem diarreia, pneumonia, linfopenia, linfócitos esgotados e produção de citocinas pró-inflamatórias. A imunologia faz parte do processo de
evolução clínica, mas existem algumas questões em torno da proteção baseada na imunidade: (1) por que algumas pessoas infectadas apresentam apenas sintomas leves da doença ou são assintomáticas; (2) por que as respostas tardias e fracas de anticorpos estão associadas a desfechos graves; e (3) por que a positividade em testes moleculares não representa
anticorpo protetor IgG. Talvez as respostas das células T possam ser a chave para resolver essas questões. As células T de memória específicas para SARS-CoV-2 persistem no sangue periférico e podem ser capazes de fornecer informações eficazes sobre imunidade protetora. Os estudos com células T podem ser úteis na elucidação dos caminhos para o desenvolvimento de vacinas,
terapias e diagnósticos para COVID-19 e para preencher essas lacunas de conhecimento em imunologia.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of
clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent
protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines,
therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps
Diagnostic parameters and reliability of four rapid immunochromatographic tests for dengue 4
Background: Although performance of rapid immunochromatographic tests (RITs) for dengue virus (DENV) serotypes 1, 2 and 3 is relatively settled, evidence on accuracy of RITs for DENV-4 are based on studies with small sample sizes and with discrepant results. Objectives: To assess accuracy and inter-observer agreement of RITs targeting dengue nonstructural protein-1 (NS1) antigen - Dengue NS1-BioeasyTM, Dengue NS1 Ag Strip-Bio-RadTM, IVB Dengue Ag NS1-OrangelifeTM and Dengue NS1-K130-BioclinTM in DENV-4 samples. Methods: Study sample (n= 324) included adults presenting at an emergency unit in Rio de Janeiro, Brazil, with fever of ≤72h and two or more dengue symptoms. A serum sample from each patient was tested by each RIT. A positive reverse-transcription polymerase chain reaction was considered as the reference standard for dengue diagnosis. The diagnostic parameters analyzed for each RIT were sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Each RIT was read by homogeneous (two junior nurses) or heterogeneous (one junior nurse and one senior biologist) pairs. Agreement was estimated by simple kappa with 95% confidence interval, positive (Ppos) and negative (Pneg) proportion concordance and prevalence and bias adjusted kappa, rated from poor (k < 0.0) to almost perfect (0.8 < k < 1.0), and perfect (k = 1). Results: NS1 RITs for DENV-4 diagnosis showed high specificity (95.9%–99.4%), but low sensitivity (14.7%–45.4%). BioeasyTM had the best performance, with a positive likelihood ratio of 26.0 (95% CI: 8.4;81.0). Inter-observer agreement was almost perfect for all evaluated RITs. Mismatches in confirmed dengue were more common for the BioclinTM (Ppos 88.3–90.0 %) and OrangelifeTM (Ppos 91.7–94.1 %) tests.2051-01-0
Proteins involved in the biosynthesis of lipophosphoglycan in Leishmania: a comparative genomic and evolutionary analysis
Fundação de Amparo à
Pesquisa do Estado da Bahia (Iniciação Científica FAPESB, process number
3645/2018) and is a current recipient of a Master’s scholarship from FAPESB
(process number BOL0159/2019). LAS was supported by Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq, process number
152107/2018-5). ATLQ acknowledges funding from Fundação Oswaldo Cruz
(INOVA - process VPPIS-001-FIO-18-45). The study was supported in part by an
intramural grant from the Instituto Gonçalo Moniz awarded to PIPR.Leishmania spp. are digenetic parasites capable of infecting humans and causing a range of diseases collectively known as leishmaniasis. The main mechanisms involved in the development and permanence of this pathology are linked to evasion of the immune response. Crosstalk between the immune system and particularities of each pathogenic species is associated with diverse disease manifestations. Lipophosphoglycan (LPG), one of the most important molecules present on the surface of Leishmania parasites, is divided into four regions with high molecular variability. Although LPG plays an important role in host-pathogen and vector-parasite interactions, the distribution and phylogenetic relatedness of the genes responsible for its synthesis remain poorly explored. The recent availability of full genomes and transcriptomes of Leishmania parasites offers an opportunity to leverage insight on how LPG-related genes are distributed and expressed by these pathogens. Results: Using a phylogenomics-based framework, we identified a catalog of genes involved in LPG biosynthesis
across 22 species of Leishmania from the subgenera Viannia and Leishmania, as well as 5 non-Leishmania trypanosomatids.
The evolutionary relationships of these genes across species were also evaluated. Nine genes related to
the production of the glycosylphosphatidylinositol (GPI)-anchor were highly conserved among compared species,
whereas 22 genes related to the synthesis of the repeat unit presented variable conservation. Extensive gain/loss
events were verified, particularly in genes SCG1-4 and SCA1-2. These genes act, respectively, on the synthesis of the
side chain attached to phosphoglycans and in the transfer of arabinose residues. Phylogenetic analyses disclosed
evolutionary patterns reflective of differences in host specialization, geographic origin and disease manifestation.
Conclusions: The multiple gene gain/loss events identified by genomic data mining help to explain some of the
observed intra- and interspecies variation in LPG structure. Collectively, our results provide a comprehensive catalog
that details how LPG-related genes evolved in the Leishmania parasite specialization process