Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

O metabolismo tumoral de chalconas como alvo terapêutico no câncer de mama

Orientadora: Profª. Drª. Alexandra AccoCoorientadora: Profª. Drª. Edneia A. S. R. CavalieriTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia. Defesa : Curitiba, 30/09/2021Inclui referências: p. 98-114Resumo: O câncer pode ser considerado um desafio inerente ao aumento da longevidade humana e estilo de vida atual. Observa-se, sobretudo, um crescimento notável nos casos de câncer de mama, considerado o tipo mais diagnosticado no mundo. Os impactos desta condição não se limitam à perda de qualidade de vida das mulheres vítimas da doença, principal público deste tipo de câncer, mas é também considerado um problema de saúde pública emergente. O remodelamento metabólico é uma das bases da transformação celular maligna e, por isso, um alvo interessante para a terapia anticâncer, utilizado em associação com outras modalidades terapêuticas para otimizar o tratamento e superar a resistência adquirida aos fármacos. Uma via clássica de plasticidade metabólica é do mTOR, um propulsor da biossíntese de macromoléculas que garante o crescimento e divisão celular. Esta via, dentre outras, foi investigada neste trabalho como possível alvo da chalcona sintética 4-nitrochalcona (4NC). A 4NC apresentou um efeito antiproliferativo em modelo in vitro de câncer de mama (linhagem MCF-7), associado à atenuação de Raptor e S6K1, efetores a jusante de mTOR, com consequente redução da síntese proteica; além de queda da razão lactato/piruvato, um indicador importante da glicólise aeróbica ou efeito Warburg. Adicionalmente, o potencial anticâncer da 4NC foi confirmado in vivo no carcinoma sólido de Ehrlich, com administração de 4NC por via oral, na dose de 25 mg kg-1 ao dia por 21 dias. Em ambos os modelos, houve também um incremento gênico e proteico dos níveis de LC3, um marcador autofágico. No entanto, demonstrou-se in vitro que os níveis de outros efetores autofágicos como p62 e Beclina-1 não se alteraram, sugerindo um efeito de bloqueio da autofagia mediado pela 4NC. Portanto, a 4NC apresenta efeito dual na modulação metabólica tumoral. Afora as vias de metabolismo clássicas, novos marcadores de interesse neste campo despontam, como é o caso da enzima 6-fosfofruto-2-quinase/frutose-2,6-bifosfatase 3 (PFKFB3). Trata-se de uma potente fomentadora do efeito de Warburg, com atividade enzimática colateral à glicólise. Tendo em vista a heterogeneidade do câncer de mama em termos de classificação morfológica, molecular e comportamento clínico, fez-se uma revisão de literatura para avaliar os benefícios da terapia anti-PFKFB3 no câncer de mama, com destaque para as chalconas 3PO, PFK15 e PFK158. Cada subtipo de câncer de mama apresentou uma resposta característica, vinculada principalmente às vias de sinalização PI3K/AKT/mTOR e MAPK e ao status hormonal. Independente do contexto de modulação metabólica, anti-mTOR ou anti-PFKFB3, as chalconas se mostram como possibilidades consistentes de terapia no câncer de mama, especialmente com base em estudos pré-clínicos.Abstract: Cancer can be considered an inherent challenge to increasing human longevity and current lifestyle. In particular, there is a remarkable growth in cases of breast cancer, considered the most diagnosed cancer in the world. The impacts of this condition are not limited to the loss of quality of life of women victims of the disease, but it is seen as an emerging public health problem. Metabolic remodeling is one of the bases of malignant cell transformation and, therefore, an interesting target for anticancer therapy, used in association with other therapeutic modalities to optimize treatment and overcome acquired resistance to drugs. A classic pathway of metabolic plasticity is mTOR, a macromolecule biosynthesis booster that ensures cell growth and division. This pathway was investigated herein as a possible action mechanism of the synthetic chalcone 4-nitrochalcone (4NC). 4NC showed an antiproliferative effect in an in vitro model of breast cancer (MCF-7 cells lineage), associated with attenuation of Raptor and S6K1, downstream effectors of mTOR, with a consequent reduction in protein synthesis; in addition to a drop in the lactate/pyruvate ratio, an important indicator of aerobic glycolysis or Warburg's effect. Additionally, the anticancer potential of 4NC was confirmed in vivo using the solid Ehrlich carcinoma model, with oral administration of 4NC at a dose of 25 mg kg-1 per day. In both models, there was also an increase in gene and protein levels of LC3, an autophagic marker. However, it was demonstrated in vitro that the levels of other autophagic effectors such as p62 and Beclin-1 did not change, suggesting a 4NCmediated autophagy blocking effect. Therefore, 4NC has a dual and synergistic effect on tumor metabolic modulation. Apart from the classical metabolism pathways, new markers of interest in this field are arising, such as the enzyme 6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase 3 (PFKFB3). It is a potent promoter of the Warburg effect, with enzymatic activity that is collateral to glycolysis. Considering the heterogeneity of morphological, molecular classification, and clinical behavior of breast tumor, a literature review was carried out to assess the benefits of anti- PFKFB3 therapy in breast cancer, with emphasis on the chalcones 3PO, PFK15, and PFK158. Each breast cancer subtype showed a characteristic response, mainly linked to the PI3K/AKT/mTOR and MAPK signaling pathways and hormonal status. Regardless of the context of metabolic modulation, anti-mTOR or anti-PFKFB3, chalcones have been shown to be consistent possibilities for breast cancer therapy at the preclinical level

Spontaneous and experimental poisoning by Tifton 68 (Cynodon Nlemfuensis Vanderyst) in cattle

Tifton 68 (Cynodon nlemfuensis Vanderyst) is a grass cultivated in southern Brazil and it causes peracute clinical manifestations of dyspnea, swallowing difficulty, muscle tremors, bloat and recumbency in cattle. After starting the first clinical signs, death occurs quickly. Gross and microscopic lesions were not observed. The present study describes the epidemiological, clinical and lesional spontaneous tifton 68 poisoning that occurred in Rio do Sul, Pouso Redondo, Taió and Rio do Campo, in Santa Catarina State. Data were obtained through information from Animal Pathology Laboratory, Centro de Ciências Agroveterinárias (LAPA / CAV) archives. Experimentally was performed the hydrocyanic acid concentration in fresh and dry leaves and treatment with specific antidote solution. The disease was experimentally reproduced with the administration of tifton 68 green leaves for two cattle in doses starting of 10.3 g/kg. The cyanogenic poisoning was confirmed by the immediate response to sodium thiosulfate and sodium nitrite intravenous treatment. Tifton 68 green leaves samples had positive response to picric acid paper test, with mild reaction, turning orange in color. Dried tifton 68 leaves showed no toxicity even at high doses (18 and 27 g/kg) being safe for cattle consumptionTifton 68 (Cynodon nlemfuensis Vanderyst) é uma gramínea cultivada na região sul do Brasil e é responsável por manifestações clínicas superagudas de dispneia, dificuldade de deglutição, tremores musculares, timpanismo e decúbito em bovinos. A morte ocorre rapidamente após o inicio dos primeiros sinais e não são encontradas alterações macro e microscópicas significativas. O presente estudo descreve os aspectos epidemiológicos, clínicos e lesionais da intoxicação espontânea por tifton 68 que ocorreu nos municípios de Rio do Sul, Pouso Redondo, Taió e Rio do Campo, estado de Santa Catarina, registrados no Laboratório de Patologia Animal do Centro de Ciências Agroveterinárias (LAPA/CAV). Experimentalmente foram avaliados a concentração de ácido cianídrico nas folhas verdes e secas dessa planta e o uso de solução antídoto específica. A reprodução experimental consistiu na administração de folhas verdes de tifton 68 para dois bovinos com doses a partir de 10,3 g/kg. O quadro de intoxicação cianogênica foi confirmado pela imediata resposta ao tratamento endovenoso com tiossulfato de sódio e nitrito de sódio. As amostras da planta verde forneceram resposta positiva ao teste do papel picro-sódico. O feno de tifton 68 não demonstrou qualquer toxicidade, mesmo em doses maiores (18 e 27 g/kg), sendo seguro para a alimentação de bovinosConselho Nacional de Desenvolvimento Científico e Tecnológic

Incidence of canine leptospirosis in the metropolitan area of Curitiba, State of Parana, Southern Brazil

Introduction The incidence of canine leptospirosis in Brazil needs to be assessed Methods The same dogs in southern Brazil were sampled over two years to determine the prevalence, incidence and association of canine leptospirosis with various risk factors. Results In 2009, the prevalence was 33 (14.4%) of 228 dogs, with a predominance of serovar Canicola (33.4%). In 2010, 90 dogs were re-evaluated (the remaining dogs were lost to deaths, address changes and donations), and the prevalence was found to be 35 (38.9%) of 90, with the predominant serovar being Icterohaemorrhagiae (51.4%). Moreover, the incidence was 26 of 90 (28.9%), and the disease was statistically associated with age (2009) and street access (2010). Conclusions Our findings revealed instability in the dog population and age to be relevant risk factors for canine leptospirosis

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. Discussion: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV