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Clinical and Biochemical Features of Hypopituitarism Among Brazilian Children With Zika Virus–Induced Microcephaly
No full textThe Zika virus infects progenitor neuron cells, disrupts cerebral development, and, in
mice, drives hypothalamic defects. Patients with microcephaly caused by congenital Zika infection
present with midline cerebral defects, which may result in hypopituitarism.
OBJECTIVE To analyze postnatal growth and the presence of clinical and biochemical features
associated with hypopituitarism in children with congenital Zika infections.
DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study at 2 public referral
hospitals in Bahia, Brazil, specializing in the treatment of congenital Zika infection, clinical data and
growth parameters of 65 patients with the infection were evaluated. Data were analyzed from April
2017 through July 2018.
EXPOSURE Congenital Zika infection.
MAIN OUTCOMES AND MEASURES Length, weight, and head circumference were measured at
birth and during follow up (ie, at 27 months of life) for each patient. Basal levels of free thyroxine,
thyrotropin, cortisol, corticotropin, prolactin, insulin-like growth factor 1, insulin-like growth factor
binding protein 3, urine and plasma osmolality, electrolytes, glucose, and insulin were evaluated at
the age of 26 months to 28 months. All patients underwent central nervous system computed
tomography scans and ophthalmic and otoacoustic evaluations at the time of this investigation or
had done so previously.
RESULTS Among 65 patients (38 [58.4%] male; median [interquartile range] age at enrollment, 27
[26-28] months), 61 patients presented with severe brain defects (93.8%), including corpus callosum
agenesis or hypoplasia (ie, midline brain defects; 25 patients [38.5%]) and optic nerve atrophy (38
patients [58.5%]). Most patients presented with severe neurodevelopmental delay (62 of 64
patients [96.9%]). Past or present clinical signs of hypopituitarism were rare, occurring in 3 patients
(4.6%). Severe microcephaly, compared with mild or moderate microcephaly, was associated with
a shorter length by median (interquartile range) z score at birth (−1.9 [−2.5 to −1.0] vs −0.3 [−1.0 to 0];
P < .001), but this difference did not persist at 27 months (−1.6 [−2.3 to −0.3] vs −2.9 [−4.0 to −1.2];
P = .06). Growth hormone deficiency or hypothyroidism were not observed in any patients, and
glucose and insulin levels were within reference ranges for all patients. Low cortisol levels (ie, below
3.9 μg/dL) were observed in 4 patients (6.2%). These 4 patients presented with low (ie, below 7.2
pg/mL) or inappropriately low (ie, below 30 pg/mL) corticotropin levels. Low corticotropin levels (ie,
below 7.2 pg/mL) were observed in 6 patients (9.2%). Diabetes insipidus was evaluated in 21
patients; it was confirmed in 1 patient (4.8%) and suggested in 3 patients (14.3%). CONCLUSIONS AND RELEVANCE This study found that congenital Zika infection with
microcephaly was associated with midline brain defects and optic nerve atrophy. Children with
congenital Zika infections presented with prenatal growth impairments with a lack of postnatal
catch-up, as shown by persistent short length from birth until 27 months; these impairments were
not associated with growth hormone deficiency. Patients also presented with severe developmental
delay thatwas not associated with hypothyroidism, while central adrenal insufficiency and diabetes
insipidus occurred in some patients
Multi-Omic Analysis of Symbiotic Bacteria Associated With Aedes aegypti Breeding Sites
No full textMosquito breeding sites are complex aquatic environments with wide microbial diversity and physicochemical parameters that can change over time during the development of immature insect stages. Changes in biotic and abiotic conditions in water can alter life-history traits of adult mosquitos but this area remains understudied. Here, using microbial genomic and metabolomics analyses, we explored the metabolites associated with Aedes aegypti breeding sites as well as the potential contribution of Klebsiella sp., symbiotic bacteria highly associated with mosquitoes. We sought to address whether breeding sites have a signature metabolic profile and understand the metabolite contribution of the bacteria in the aquatic niches where Ae. aegypti larvae develop. An analysis of 32 mosquito-associated bacterial genomes, including Klebsiella, allowed us to identify gene clusters involved in primary metabolic pathways. From them, we inferred metabolites that could impact larval development (e.g., spermidine), as well as influence the quality assessment of a breeding site by a gravid female (e.g., putrescine), if produced by bacteria in the water. We also detected significant variance in metabolite presence profiles between water samples representing a decoupled oviposition event (oviposition by single females and manually deposited eggs) versus a control where no mosquito interactions occurred (PERMANOVA: p < 0.05; R 2 = 24.64% and R 2 = 30.07%). Five Klebsiella metabolites were exclusively linked to water samples where oviposition and development occurred. These data suggest metabolomics can be applied to identify compounds potentially used by female Ae. aegypti to evaluate the quality of a breeding site. Elucidating the physiological mechanisms by which the females could integrate these sensory cues while ovipositing constitutes a growing field of interest, which could benefit from a more depurated list of candidate molecules
Characterization of a recombinant mycobacterial L-asparaginase produced in Escherichia coli
No full textOs autores externos submeteram sua publicação para apresentação de trabalho no evento “International Symposium on Immunobiologicals”, que foi coordenado e organizado pelo Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), da Fundação Oswaldo Cruz
Estudo das proteases fibrinolíticas de bactérias e fungos da Coleção Biológica da Fiocruz Amazônia-CBILMD: caracterização bioquímica e expressão recombinante da enzima fibrinolítica de Serratia marcescens
No full textA pesquisa de agentes fibrinolíticos tem sido direcionada para a descoberta de proteases microbianas com atividade semelhante à da plasmina para propor agentes trombolíticos alternativos para o tratamento da trombose. A trombose é caracterizada pela formação de coágulo sanguíneo, composto por fibrina, responsável por causar a obstrução na parede do vaso, sendo considerada uma das principais causas de doenças cardiovasculares da vida moderna. Com isso, o objetivo desse estudo foi identificar proteases fibrinolíticas de bactérias e fungos estocados no acervo da Coleção Biológica da Fiocruz Amazônia (CBILMD) e selecionar uma biomolécula com potencial terapêutico para posterior expressão sob forma recombinante em E. coli. Para investigar a atividade fibrinolítica, foram reativados 150 fungos da coleção e foram isoladas 150 bactérias de solo e água do bioma Amazônia. As culturas foram submetidas a fermentação submersa para obtenção do filtrado de cultura e posterior realização dos testes enzimáticos: placa de ágar leite, placa de fibrina e quantificação da atividade fibrinolítica. Para a produção e caracterização das enzimas fibrinolíticas nativas, os cinco microrganismos que apresentaram maior produção de protease seguiram para as etapas de análise temporal da secreção enzimática, purificação, testes fibrinolíticos, caracterização bioquímica das enzimas quanto ao efeito do pH, temperatura, íons metálicos e inibidores enzimáticos e teste de hemólise. Para a produção da enzima recombinante, selecionou-se Serratia marcescens CBAM 519 para identificação do gene codante para protease fibrinolítica. O material foi analisado na Plataforma de Sequenciamento de Ácidos Nucleicos de Nova Geração (FIOCRUZ/IOC – RJ) O gene de S. marcescens CBAM 519 (sm519) que codifica a enzima fibrinolítica SM519 foi obtido por PCR e clonado no vetor de expressão pET23a(+). Os resultados demonstram que as enzimas nativas de Penicillium citrinum CFAM 521, P. citrinum CFAM 592, Aspergillus flavus CFAM 367, Serratia marcescens CBAM 519 e Pseudomonas aeruginosa CBAM 529 apresentaram pH e temperatura ótimos de 9 e 37°C, respectivamente, com atividade reduzida na presença de Cu2+ e potencializada na presença de Mn2⁺. As enzimas não apresentaram atividade hemolítica, não ativaram o plasminogênio e hidrolisaram efetivamente a fibrina e o fibrinogênio, degradando rapidamente todas as cadeias de fibrinogênio (Aα, Bβ e γ). O peso molecular das enzimas variou entre 35 e 56 kDa. As enzimas de P. citrinum CFAM 521 e CFAM 592 foram classificadas como serina proteases, enquanto as enzimas de A. flavus CFAM 367, S. marcescens e Pseudomonas aeruginosa CBAM 529 como metalo-serino proteases. A enzima de S. marcescens CBAM foi expressa com sucesso em E. coli cepa BL21(DE3) na fração insolúvel, em corpos de inclusão, mas renaturado com sucesso, com peso molecular de aproximadamente 55kDa. A expressão em sistema heterólogo preservou as características da enzima nativa, sem causar mudanças expressivas nos parâmetros físico-químicos. A enzima recombinante (rSM519) manteve sua ação fibrinolítica e fibrinogenolítica, especialmente na clivagem das cadeias α e β e compartilha características de protease semelhante à plasmina. Todas essas características combinadas levam à conclusão de que a protease fibrinolítica recombinante de S. marcescens CBAM 519 (rSM519) apresenta potencial para uso como agente terapêutico no tratamento e prevenção da tromboseResearch on fibrinolytic agents has been oriented towards the discovery of microbial proteases with plasmin-like activity to propose alternative thrombolytic drugs for thrombosis treatment. Thrombosis is characterized by the formation of a blood clot, composed of fibrin, responsible for causing obstruction in the vessel wall, being considered one of the main causes of cardiovascular diseases in modern life. Thus, the aim of this study was to identify fibrinolytic proteases from bacteria and fungi stored in the collection of the Fiocruz Amazônia Biological Collection (CBILMD) and to select a biomolecule with therapeutic potential for further expression in recombinant form in E. coli. To investigate fibrinolytic activity, 150 fungi from the collection were reactivated and 150 soil and water bacteria from the Amazon biome were isolated. The cultures were subjected to submerged fermentation to obtain the culture filtrate and subsequent enzymatic tests on milk agar plates, fibrin plates and quantification of fibrinolytic activity. For the production and characterization of native fibrinolytic enzymes, the five microorganisms that showed the highest production of protease followed the steps of temporal analysis of enzyme secretion, enzyme purification, fibrinolytic tests, biochemical characterization as to the effect of pH, temperature, metal ions and enzyme inhibitors and hemolysis test. To produce the recombinant enzyme, Serratia marcescens CBAM 519 was selected to identify the coding gene for fibrinolytic protease. The material was analyzed in the Next Generation Nucleic Acid Sequencing Platform (FIOCRUZ / IOC - RJ) The sm519 gene that encodes the fibrinolytic enzyme SM519 was obtained by PCR and cloned into the expression vector pET28a (+). The results show that the native enzymes from Penicillium citrinum CFAM 521, P. citrinum CFAM 592, Aspergillus flavus CFAM 367, Serratia marcescens CBAM 519 and Pseudomonas aeruginosa CBAM 529 showed optimum pH and temperature of 9 and 37°C, respectively, reduced activity in the presence of Cu2+ and improved activity in the presence of Mn2⁺. The enzymes did not show hemolytic activity, did not activate plasminogen and hydrolyzed fibrin and fibrinogen efficiently, rapidly degrading all fibrinogen chains (Aα, Bβ and γ). The molecular weight of the enzymes varied between 35 and 56 kDa. The enzymes from P. citrinum CFAM 521 and CFAM 592 were classified as serine proteases, while the enzymes from A. flavus CFAM 367, S. marcescens and Pseudomonas aeruginosa CBAM 529 were classified as metalloserine proteases. The enzyme from S. marcescens CBAM 519 was successfully expressed in E. coli in the insoluble fraction, in inclusion bodies, but succesfully renaturated, with an apparent molecular mass of 55kDa. The expression in a heterologous system preserved the characteristics of the native enzyme, without causing significant changes in the physicalchemical parameters. The recombinant enzyme (rSM519) maintained its fibrinolytic and fibrinogenolytic action, especially in the cleavage of α and β chains, and shares characteristics of a plasmin type protease. All these characteristics combined lead to the conclusion that the recombinant fibrinolytic protease from S. marcescens CBAM 519 has potential for use as a therapeutic agent in the treatment and prevention of thrombosis2150-08-2
Prevalence and sociodemographic factors associated with heavy drinking in Brazil: crosssectional analyses of the National Health Survey
No full textObjetivo: Este estudo teve o objetivo de caracterizar o hábito de beber pesado na população brasileira, utilizando os dados das duas edições da Pesquisa Nacional de Saúde 2013 e 2019. Métodos: O tamanho das amostras em 2013 e 2019 foi de 60.202 e 88.943 indivíduos de 18 anos ou mais, respectivamente. Foram estimadas as prevalências do hábito de beber pesado (definido por 8 ou mais doses por semana para as mulheres e 15 ou mais doses para os homens) e os intervalos de confiança por sexo, faixa etária, grau de escolaridade, cor da
pele/raça, estado civil e situação de residência (urbana/rural). Foram usados modelos de regressão de Poisson para comparar as prevalências. Resultados: 6,1% dos brasileiros tinham o hábito de beber pesado em 2013 e 7,3% em 2019. Nas duas edições da Pesquisa Nacional de Saúde, observou-se um gradiente de diminuição do beber pesado durante a vida, com as maiores prevalências entre os adultos jovens, entre os homens, com baixo nível de escolaridade, entre os solteiros e residentes da área urbana. Conclusões: As altas prevalências
encontradas expõem a necessidade de considerar o hábito de beber pesado como um fator de risco à saúde da população brasileira e a urgência em adotar estratégias para a sua diminuição.Objective: This article aims to characterize the heavy drinking behavior in the Brazilian population, using data from the two editions of the “National Health Survey” (PNS), 2013 and 2019. Methods: The sample sizes in 2013 and 2019 were 60,202 and 88,943 individuals aged 18 years or older, respectively. The prevalence of the habit of heavy drinking (defined as 8 or more doses per week for women, and 15 or more doses for men) was estimated, and the confidence intervals were defined by sex, age group, schooling, skin color/race, marital status and household status (urban/rural). Poisson regression models were used to compare prevalence rates. Results: 6.1% of Brazilians were heavy drinkers in 2013, and 7.3% in 2019. In the two editions of the PNS there was a gradient of reduction in heavy drinking throughout life, being the highest prevalence among young adults, men, with low schooling, single and living in the urban area. Conclusions: The high prevalence rates expose the need to consider the habit of heavy drinking as a risk factor for the health of the Brazilian
population, and the urgency to adopt strategies to reduce it
CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions
No full textIn the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI (A1 class) from cases with other illnesses (C class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1b, IL-6 and TNF-a were observed in YEL-AEFI (A1 and C classes) as compared to primary vaccines without YEL-AEFI [PV(day 3-28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1b, IL-15, IL-1Ra and G-CSF were found in A1 as compared to C class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate A1 from C. Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify A1 followed by VEGF as branch nodes to discriminate Wild Type YFV infection (C(WT-YFV)) from cases with other illnesses (C*). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases
Social determinants associated with Zika virus infection in pregnant women
No full text1 Instituto de Sau´de Coletiva, Universidade Federal da Bahia, Salvador, Brazil, 2 Instituto Gonc¸alo Moniz,
Fundac¸ão Oswaldo Cruz, Ministe´ rio da Sau´de, Salvador, Brazil, 3 Department of Epidemiology of Microbial
Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America, 4 Precision
Vaccines Program, Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts,
United States of America, 5 Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA–
Brazil, 6 Development and Innovation Center, Laboratory of Virology, Butantan Institute, São Paulo, Brazil,
7 Departamento de Microbiologia. Instituto de Ciências Biome´dicas, Universidade de São Paulo, São Paulo,
Brazil, 8 Laborato´ rio de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências
Biome´dicas, Universidade de São Paulo, São Paulo, Brazil, 9 Scientific Platform Pasteur USP, São Paulo,
BrazilNational Institutes of Health (NIAID R01
AI052473 (AK), R25 U01AI088752 (AK), FIC R01
TW009504 (AK), R25 TW009338 (AK), F31
AI114245 (AK), R01 AI121207 (AK) (www.niaid.
nih.gov/), Wellcome Trust (102330/Z/13/Z (FC);
218987/Z/19/Z (FC) (www.wellcome.ac.uk/), Bahia
State Research Support Foundation - FAPESB ZIKA-FAPESB T.O. n˚ PET0021/2016 (MGR) (www.
fapesb.ba.gov.br), Coordination for the
Improvement of Higher Education – CAPES, from
Brazil-Finance Code 001 (scholarship to JPAT),
(www.capes.gov.br/), the São Paulo Research
Foundation – FAPESP (LCSF) (www.fapesp.br),
under Project 2016/20045-7 and the European
Union’s Horizon 2020 research and innovation
programme under Grant Agreement No. 734584
(DBA) (www.ec.europa.eu).This study aims to describe the sociodemographic determinants associated with
exposure to Zika Virus (ZIKV) in pregnant women during the 2015–2016 epidemic in Salvador,
Brazil.
Methods
We recruited women who gave birth between October 2015 and January 2016 to a
cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information
on their demographic, socioeconomic, and clinical characteristics, and evaluated
their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was
then used to assess the relationship between these social determinants and ZIKV exposure
status.
Results
We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate
analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04–
1.35) and food insecurity (aPR 1.17; 95%CI 1.01–1.30) were positively associated with
ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR
0.99; 95%CI 0.97–0.998). Conclusion
Eve after controlling for age, differences in key social determinants, as education and food
security, were associated with the risk of ZIKV infection among pregnant women in Brazil.
Our findings elucidate risk factors that can be targeted by future interventions to reduce the
impact of ZIKV infection in this vulnerable population
Development of Analytical Methodology by High-Performance Liquid Chromatography to Curcuminoids Quantification
No full textTurmeric (Curcuma longa L.) is a species that has attracted great interest for containing bioactive
curcuminoids that have some pharmacological and physiological activities. Among them, antimalarial,
anti-inflammatory, antidepressant and anticancer effects that are mainly attributed to curcumin,
demethoxycurcumin and bisdemethoxycurcumin stand out. This work aimed the development of an
analytical methodology to optimization of the best conditions for sample preparation, chromatographic
separation, detection, identification and quantification of curcumin, demethoxycurcumin and
bisdemethoxycurcumin. The samples were weighed and solubilized to obtain a 200 μg/mL solution,
analyzed in triplicate, using the following chromatographic parameters: flow rate at 1.2 mL/min;
temperature at 50 oC; detection at 420 nm; total analysis time of 25 min and injection volume of 20 μL.
The developed method showed good selectivity, resolution, signal symmetry and capacity factor for
curcuminoids analysis. It is worth noting that the new method developed showed a scientific gain for
being more efficient and with the change of column, there was a gain in selectivity and resolution for the
separation of curcuminoids. In addition, the silica column modified with phenyl groups has a phase of
medium polarity and has greater selectivity in the separation of aromatic compounds
App-based symptom tracking to optimize SARS-CoV-2 testing strategy using machine learning
No full textBackground: Tests are scarce resources, especially in low and middle-income countries, and the optimization of testing programs during a pandemic is critical for the effectiveness of the disease control. Hence, we aim to use the combination of symptoms to build a predictive model as a screening tool to identify people and areas with a higher risk of SARS-CoV-2 infection to be prioritized for testing. Materials and methods: We performed a retrospective analysis of individuals registered in "Dados do Bem," a Brazilian app-based symptom tracker. We applied machine learning techniques and provided a SARS-CoV-2 infection risk map of Rio de Janeiro city. Results: From April 28 to July 16, 2020, 337,435 individuals registered their symptoms through the app. Of these, 49,721 participants were tested for SARS-CoV-2 infection, being 5,888 (11.8%) positive. Among self-reported symptoms, loss of smell (OR[95%CI]: 4.6 [4.4-4.9]), fever (2.6 [2.5-2.8]), and shortness of breath (2.1 [1.6-2.7]) were independently associated with SARS-CoV-2 infection. Our final model obtained a competitive performance, with only 7% of false-negative users predicted as negatives (NPV = 0.93). The model was incorporated by the "Dados do Bem" app aiming to prioritize users for testing. We developed an external validation in the city of Rio de Janeiro. We found that the proportion of positive results increased significantly from 14.9% (before using our model) to 18.1% (after the model). Conclusions: Our results showed that the combination of symptoms might predict SARS-Cov-2 infection and, therefore, can be used as a tool by decision-makers to refine testing and disease control strategies
El colectivo TiVi Piraí: salud mental e comunicación
No full textIlka de Araujo Soares da Prefeitura de Juiz de Fora, do Trabalharte - Associação Pró-Saúde Mental teve seu artigo submetido e aprovado na edição da RECIIS - Dossiê Feminismos: perspectivas em comunicação e informação em saúde, parte 2 v. 15 n.3 (2021)O trabalho apresenta o Coletivo TiVi Piraí, um coletivo de comunicação e saúde mental ativo desde 2013, composto por usuários da Rede de Atenção Psicossocial de Juiz de Fora (MG). Trata-se do relato de uma experiência que se articula aos movimentos contemporâneos de grupalidades e que intenciona mudanças e melhorias nas políticas públicas no contexto da reforma psiquiátrica. Discorre sobre o percurso histórico de formação do grupo, contextualizado no processo de desinstitucionalização do município. O texto demonstra a importância do espaço de democratização da comunicação como recurso de estabelecimento de diálogo sociocultural e de reconstrução do imaginário estigmatizante e excludente acerca do portador de sofrimento mental. São apresentados aspectos de produção subjetiva na trajetória existencial dos integrantes da iniciativa, como também o acesso ao protagonismo, expressividade e exercício da cidadania.The paper presents the Collective TiVi Piraí, a communication and mental health collective active since 2013 composed of Psychosocial Care Network of Juiz de Fora (MG) users. It frames the experience report linked to contemporary group movements that intend to change and improve public policies in the psychiatric reform context. It discusses the historical path of the group formation contextualized in the process of the municipality’s deinstitutionalization. The text shows the importance of the communication space democratization as a resource for the establishment of socio-cultural dialogue and the reconstruction of the stigmatizing and excluding imaginary about the carrier of mental suffering. The aspects of subjective production are presented within the existential trajectory of the initiative members and the possibility of access to protagonism, expressiveness and citizenship exercise.El trabajo presenta el Colectivo ‘TiVi Piraí’, un colectivo de comunicación y salud mental activo desde 2013, compuesto por usuarios de la Red de Atención Psicosocial de Juiz de Fora (MG). Se trata del relato de una experiencia que se articula en los movimientos contemporáneos de grupos que intentan producir cambios y mejorías de las políticas públicas, en el contexto de la reforma psiquiátrica. Transcurre sobre el camino histórico de formación del grupo, contextualizado en el proceso de desinstitucionalización del municipio. El texto muestra la importancia del espacio democrático en la comunicación como un recurso para establecer el diálogo sociocultural y también de reconstrucción del imaginario que estigmatiza y excluye al portador de sufrimiento mental. Son presentados los aspectos más significativos de la producción subjetiva en la trayectoria existencial de los integrantes de la iniciativa, simultáneamente con la posibilidad de acceso al protagonismo, expresividad y ejercicio de la ciudadanía