Thalidomide and birth defects

Apologies to the many papers we were unable to cite, due to space constraints. We thank Lynda Erskine, Shaunna Beedie and Chris Mahony for helpful discussions. Lucas Rosa Fraga is funded by a PhD scholarship from the Science without Borders program - CNPq Brazil - INAGEMP/ Grant CNPq 573993/2008-4. Alex J. Diamond is funded by a BBSRC DTP PhD Scholarship.Peer reviewedPostprin

Bullying Involvement and Physical Pain Between Ages 10 and 13 Years: Reported History and Quantitative Sensory Testing in a Population-Based Cohort

We aimed to quantify the prospective association between bullying and physical pain in a population-based cohort of adolescents. We assessed 4,049 participants of the 10 and 13 years waves of the Generation XXI birth cohort study in Portugal. Pain history was collected using the Luebeck pain screening questionnaire. A subsample of 1,727 adolescents underwent computerized cuff pressure algometry to estimate pain detection/tolerance thresholds, temporal pain summation and conditioned pain modulation. Participants completed the Bully Scale Survey and were classified as “victim only”, “both victim and aggressor”, “aggressor only”, or “not involved”. Associations were quantified using Poisson or linear regression, adjusted for sex and adverse childhood experiences. When compared to adolescents “not involved”, participants classified as “victim only” or “both victim and aggressor” at age 10 had higher risk of pain with psychosocial triggers, pain that led to skipping leisure activities, multisite pain, pain of higher intensity, and pain of longer duration, with relative risks between 1.21 (95% confidence interval: .99, 1.49) and 2.17 (1.57, 3.01). “Victims only” at age 10 had lower average pain detection and tolerance thresholds at 13 years (linear regression coefficients: −1.81 [−3.29, −.33] and −2.73 [−5.17, −.29] kPa, respectively), as well as higher pain intensity ratings (.37 [.07, .68] and .39 [.06, .72] mm), when compared with adolescents not involved. No differences were seen for the remaining bullying profiles or sensory measures. Our findings suggest that bullying may have long-term influence on the risk of chronic musculoskeletal pain and may interfere with responses to painful stimuli. Perspective: We found prospective evidence that bullying victimization in youth: 1) is more likely to lead to negative reported pain experiences than the reverse, 2) may have long-term influence on adverse pain experiences, and 3) may contribute to pain phenotypes partly by interfering with somatosensory responses to painful stimuli. © 2023 The AuthorsThe authors have no conflicts of interest to disclose. This work was supported by a research grant from FOREUM Foundation for Research in Rheumatology (Career Research Grant). This study was also funded by the Foundation for Science and Technology of the Portuguese Ministry of Science, Technology and Higher Education, through the projects “H3ARTS: Moving upstream in the determinants of cardiovascular health: A lifecourse approach using population-based cohorts from three world regions (2022.05496. PTDC)” and UNFOLD: In the shadow of violence: a life-course approach to unfold the scars on the body and mind over childhood and adolescence (2022.06837. PTDC)”. The Generation XXI cohort is funded by the Epidemiology Research Unit - Instituto de Saúde Pública, Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2019) and Laboratory for Integrative and Translational Research in Population Health (ITR) (LA/P/0064/2020), Administração Regional de Saúde—Norte (Regional Department of the Portuguese Ministry of Health) and Calouste Gulbenkian Foundation. MT was funded by the ERDF, through the North Regional Operational Program in the framework of the project HEALTH-UNORTE (NORTE-01–0145-FEDER-000039)

As novas tecnologias de comunicação e informação : o uso das mídias sociais como ferramenta no processo de ensino e aprendizagem

Monografia (graduação)—Universidade de Brasília, Faculdade de Educação, Curso de Graduação em Pedagogia, 2012.Este trabalho teve como objetivo demonstrar que o uso das mídias sociais integradas a um conjunto de ações presenciais contribui para tornar mais atrativo o processo de ensino e aprendizagem. A partir de uma análise atual da influência que o computador, a internet e as novas tecnologias de informação e comunicação exerce no aluno, é apresentado o projeto “Brasília 50 anos em 5 perspectivas”. O trabalho contém estratégias para que o professor aborde um conteúdo curricular através de outras plataformas, como o Facebook e o Twitter. Os alunos, pela proposta, irão interagir com as personalidades históricas da construção da capital. As ações que terminam de compor a proposta de projeto envolvem pesquisa e produção de conteúdo a partir do Museu Virtual da UnB e aulas expositivas do professor. São colocadas, propostas de atividades e avaliação. O projeto foi apresentado a um grupo de professores, que expuseram suas reflexões específicas sobre o trabalho e também, em geral, à criação de novas formas de integrar as ferramentas atuais ao contexto escolar. Espera-se que as reflexões deste trabalho ajudem a suscitar a importância de repensar a forma de atrair a atenção do aluno para a escola, melhorando, consequentemente, o processo de ensino e aprendizagem.This project has as objective to demonstrate how social media integrated to a series of classroom activities contributes to make both teaching as well as learning process more interesting. Starting from a current analysis of computer's influence, internet and new information and communication technology on students, the project "Brasilia 50 years in 5 perspectives" is presented. The paper contains strategies that empower teachers to approach school content through other platforms such as Facebook and Twitter. Students, according to the proposal, will interact with historical personalities from the period when the capital was built. The final actions on the approach involve research and content production based on UnB’s Virtual Museum and explanatory classes from teachers. Activities and evaluation guidelines are presented. The Project was introduced to a group of teachers, that shared their specific reflections about the paper and also regarding creation of new ways to integrate current tools to school context It is expected that the reflections on this paper will help evoking the importance of rethinking ways to bring students closer to school, therefore enhancing the teaching and learning process

PESSOAS COM NANISMO ACONDROPLASIA: um estudo acerca dos aspectos psicossociais e as contribuições da atividade física na sua inclusão social

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Effect of partial soil wetting on transpiration, vegetative growth and root system of young orange trees

The wetted area fraction is a factor critical to the success of drip irrigation. This study aimed to evaluate the effect of partial soil wetting on transpiration, vegetative growth and root system of young orange trees. The experiment was carried out in a greenhouse where plants were grown in 0.5 m3boxes internally divided into compartments. The wetting of 12 % of soil area was tested on two types of soil cultivated with ‘Valencia’ orange trees grafted onto Rangpur lime and ‘Swingle’ citrumelo rootstocks. Transpiration was determined in 40 plants. Water extraction and root density were evaluated in the compartments. Transpiration is reduced by restriction in wetted soil area, and such reduction is influenced by the number of days after the beginning of partial irrigation, atmospheric evaporative demand and plant phenological stage. Mean transpiration of plants with partial irrigation was equivalent to 84 % of the mean transpiration of plants with 100 % of wetted soil area in the period studied. However, after 156 days of imposing partial irrigation there was no difference in transpiration between treatments. Plant acclimation was caused by an increase in root concentration in the irrigated area. After a period of acclimation, if the entire root system is wetted, soil water extraction becomes proportional to the percentage of wetted area after a short period of time. Despite the reduction in transpiration, there was no difference between treatments with 12 % and 100 % of wetted soil area in terms of vegetative growth

Adverse childhood experiences and bodily pain at 10 years of age: Findings from the Generation XXI cohort

Background: Youth and young adults with pain conditions report having a history of adverse childhood experiences (ACEs) more frequently than their healthy peers. The relationship between ACEs and pain before adolescence in population-based settings is not extensively researched. Objective: To examine the association between the history of ACEs and bodily pain at 10 years of age. Participants and setting: Cross-sectional analysis of 4738 participants of Generation XXI population-based birth cohort, recruited in 2005–06 in Porto, Portugal. Methods: Study includes self-reported data on ACEs exposures and bodily pain (pain presence, sites, and intensity a week prior to the interview). Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were obtained from binary and multinomial logistic regression analyses to estimate the likelihood of various pain features according to the extent of exposure to ACEs (i.e., 0 ACEs, 1–3 ACEs, 4–5 ACEs, and ≥ 6 ACEs). Results: Prevalence of pain, multisite, and high-intensity pain a week prior to the interview increased with increasing exposure to ACEs. After controlling for sociodemographic characteristics, children who had experienced ≥6 ACEs were more likely to report pain [AOR 3.18 (95% CI 2.19, 4.74)], multisite pain [AOR 2.45 (95% CI 1.37, 4.40)], and high-intensity pain [AOR 4.27 (95% CI 2.56, 7.12)] compared with children with no ACEs. Conclusions: A dose-response association was observed between the cumulative number of ACEs and reports of pain in 10-year-old children, suggesting that embodiment of ACEs starts as early as childhood and that pain related to ACEs begins earlier than previously reported. © 2022 Elsevier LtdFunding text 1: This work was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education under the projects “HIneC: When do health inequalities start? Understanding the impact of childhood social adversity on health trajectories from birth to early adolescence” ( POCI-01-0145-FEDER-029567 ; PTDC/SAU-PUB/29567/2017 ) and “STEPACHE: The pediatric roots of amplified pain: from contextual influences to risk stratification” ( POCI-01-0145-FEDER-029087 ; PTDC/SAU-EPI/29087/2017 ). It is also supported by Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) ( UIDB/04750/2020 ), Laboratório para a Investigação Integrativa e Translacional (ITR), Porto, Portugal ( LA/P/0064/2020 ), PhD Grant SFRH/BD/144503/2019 (to AA) funded by FCT through Fundo Social Europeu (FSE) and FCT Investigator contract CEECIND/01516/2017 (to SF). ; Funding text 2: This work was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education under the projects “HIneC: When do health inequalities start? Understanding the impact of childhood social adversity on health trajectories from birth to early adolescence” (POCI-01-0145-FEDER-029567; PTDC/SAU-PUB/29567/2017) and “STEPACHE: The pediatric roots of amplified pain: from contextual influences to risk stratification” (POCI-01-0145-FEDER-029087; PTDC/SAU-EPI/29087/2017). It is also supported by Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020), Laboratório para a Investigação Integrativa e Translacional (ITR), Porto, Portugal (LA/P/0064/2020), PhD Grant SFRH/BD/144503/2019 (to AA) funded by FCT through Fundo Social Europeu (FSE) and FCT Investigator contract CEECIND/01516/2017 (to SF)

Efeito da curcumina no tratamento de micróglias infectadas pelo vírus Zika

Dissertação (mestrado) — Universidade de Brasília, Faculdade de Medicina, Pós-graduação em Medicina Tropical, 2021.O relato de numerosos casos de microcefalia no Brasil entre 2015 e 2016 alertou a comunidade científica mundial. O principal motivo foi a sua relação com os casos de infecção pelo vírus Zika. A organização mundial da saúde alertou para a necessidade do desenvolvimento de tratamentos para a infecção e prevenções ao desenvolvimento da microcefalia. Neste contexto, a curcumina tem se mostrado uma molécula de interesse para estudos com o vírus Zika, pois há na literatura evidências da sua ação sobre os flavivírus e já está demonstrada sua capacidade anti-inflamatória. Portanto, o objetivo deste trabalho foi avaliar se a curcumina tem a capacidade de interferir nos mecanismos de morte celular e de autofagia induzidos pelo vírus e se esta molécula possui ação imunomoduladora, importante na prevenção da neuroinflamação que ocorre durante a infecção. A melhor compreensão destes mecanismos poderá contribuir para o desenvolvimento de novas medidas terapêuticas e diminuir a morbidade da infecção pelo vírus Zika. As micróglias murinas de linhagem BV2 foram infectadas com MOI 0,1 e MOI 1 do vírus Zika (cepa PE/243) e tratadas com 0,31 μM, 0,62 μM, 1,25 μM, 2,5 μM e 5 μM de curcumina. A viabilidade celular foi avaliada pelo teste de redução do MTT e lida em espectrofotômetro. A expressão da caspase-3, da mTOR e da LC3 foram avaliadas por teste antígeno- anticorpo por citometria de fluxo. A morte celular foi avaliada pela marcação por anexina/iodeto de propídio, lido em citometria de fluxo. A produção de espécies reativas de oxigênio e de nitrogênio foram avaliadas pelas sondas DCF-DA e DAF-FM, respectivamente, em citometria de fluxo. A dosagem das citocinas foi realizada por kit CBA (BD), em citometria de fluxo. Os dados mostraram que o vírus Zika apresentou um efeito citopático sobre as células BV2 e a curcumina reverteu parcialmente esta citotoxicidade. Este efeito citopático do vírus foi resultado principalmente da indução da apoptose sem aumentar a produção de caspase-3 pelas micróglias. Já a curcumina, mesmo sem alterar o número de células apoptóticas, reduziu a sinalização pela caspase-3. Observamos também que o vírus Zika induz a autofagia nas micróglias sem alterar a expressão de mTOR, enquanto o tratamento com a curcumina induziu ainda mais a autofagia através da redução da expressão de mTOR. O vírus Zika induziu uma resposta inflamatória pelas células BV2 com aumento da produção de IFN-γ, TNF-α, IL-6, IL-10, IL-17, MCP-1. Esta resposta inflamatória foi controlada pela curcumina, reduzindo a produção de IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ e TNF-α nos grupos de células infectadas com MOI 0,1 do vírus e que receberam o tratamento de 2,5 μM e 5 μM. Por fim, observamos que a infecção aumentou a produção de EROs pelas células BV2. Apenas as células estimuladas com MOI 0,1 apresentaram a produção aumentada de ERNS. Em contrapartida, células na presença de MOI 1 produziram menos ERNs. Em conclusão, observou-se que o tratamento com a curcumina apresentou um efeito pró-oxidante durante a infecção pelo vírus Zika.The report of numerous cases of microcephaly in Brazil between 2015 and 2016 have alerted the world scientific community. The main reason for it was the relation between cases of infection by zika virus. The World Health Organization alerted the need of development of treatments for the microcephaly infection and prevention. On this context, curcumin has shown itself as an interesting molecule for studies with zika virus because it has evidences of its action above flavivirus and anti-inflammatory capacity all over the literature. Therefore, the aim of the present work has been to analyze if curcumin interfered on cell death and autophagy pathways induced by the virus and if this molecule has immunomodulator action, which is important for the prevention of the neuroinflammation that happens during the infection. The best understanding of these pathways can contribute for the development of new therapeutic measures and decrease the morbidity of zika virus infection. The BV2 cell line of murine microglia were infected by MOI 0,1 e MOI 1 of zika virus (strain PE/243) and treated with 0.31 μM, 0.62 μM, 1.25 μM, 2.5 μM and 5 μM of curcumin. The cellular viability was evaluated by the test of MTT reduction and read in spectrophotometer. The expression of caspase-3, mTOR and LC3 has been evaluated by antigen-antibody test and read in flow cytometry. The cell death was evaluated by annexin/propidium iodide target and also read in flow cytometry. The production of reactive oxygen species and nitrogen was evaluated by DCF- DA and DAF-FM probes, respectively, in flow cytometry. The cytokine dosage has been done by CBA kit (BD) in flow cytometry. Our data has shown that zika virus presented a cytopathic effect in BV2 cells and curcumin has partly reversed this cytotoxicity. This cytopathic effect of the virus has happed mainly because of the induction of cell apoptosis, without increasing the production of caspase-3 by microglia. Curcumin, on the other hand, even without changing the number of apoptotic cells, has reduced the signaling by caspase-3. We also have observed that zika virus induced autophagy on microglia without changing mTOR expression, while the treatment with curcumin induced even more autophagy by the reduction of mTOR expression. Zika virus induced an inflammatory response by BV2 cells with an increase on IFN- γ, TNF-α, IL-6, IL-10, IL1-17, MCP-1 production. This inflammatory response has been controlled by curcumin, decreasing IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF- α production on groups of cells infected by virus MOI 0,1 which received the treatment of 2,5 μM and 5 μM. In the end. We have observed that the infection increased EROs production by the BV2 cells. In addiction, only cells stimulated by small amount of virus has shown increasing of ERNs production. On the other hand, cells infected by large amount of virus produced less ERNs. We have seen that the treatment with curcumin presented a pro-oxidant effect during zika virus infection

Realismo capitalista, regime de historicidade e sofrimento mental : o discurso neoliberal sobre saúde mental no relatório da OMS (2022)

A presente pesquisa busca compreender a relação entre crise de temporalidade, realismo capitalista e sofrimento mental. De forma a buscar elaborar uma relação de complemento entre a hipótese presentista de François Hartog com a noção de Realismo Capitalista apresentada por Mark Fisher. Para isso se analisa a formação hegemônica do neoliberalismo no contexto brasileiro e seus impactos na formação de um certo tipo de discurso e racionalidade que operam em um tipo específico de relação entre o passado, presente e futuro; bem como em um certo tipo de compreensão sobre o que é o sofrimento mental causado por estes. Para materializar tal ideia é analisado o Relatório Mundial sobre Saúde Mental da Organização Mundial da Saúde, buscando compreender os rastros deixados pelo realismo capitalista e o tipo de compreensão neoliberal de saúde mental individualizada e autogerenciada.This research seeks to understand the relationship between temporality crisis, capitalist realism and mental suffering. In order to seek to elaborate a complementary relationship between the presentist hypothesis of François Hartog with the notion of Capitalist Realism presented by Mark Fisher. For this, the hegemonic formation of neoliberalism in the Brazilian context is analyzed and its impacts on the formation of a certain type of discourse and rationality that operate in a specific type of relationship between the past, present and future; as well as a certain type of understanding about what is the mental suffering caused by these. To materialize this idea, the World Health Organization's World Report on Mental Health is analyzed, seeking to understand the traces left by capitalist realism and the type of neoliberal understanding of individualized and self-managed mental health

From the farm to the lab: how chicken embryos contribute to the field of teratology

Funding This study received no specific grant from any funding agency in the public, commercial or not-for402 profit sectors. Acknowlegment We would like to thank all previous researches that established chicken embryos as a really important and respected experimental model to the teratology field through the history. NV lab funded by Royal Society, Wellcome Trust, Sarcoma UK, NIH. LRF lab funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 424362/2018-0], Fundo de Incentivo a Pesquisa e Eventos (FIPE) of the Hospital de Clínicas de Porto Alegre (HCPA) [grant numbers 2019-0649 and 2017-0342] and PROPESQ/UFRGS through “Recently Hired Professors” [Call 001/2019]. The authors would like to Sophia Martins Simon de Matos for technical assistance on Figure 1 drawing.Peer reviewedPublisher PD

From the farm to the lab : how chicken embryos contribute to the field of teratology

Congenital anomalies and its causes, particularly, by external factors are the aim of the field called teratology. The external factors studied by teratology are known as teratogens and can be biological or environmental factors for example, chemicals, medications, recreational drugs, environmental pollutants, physical agents (e.g., X-rays and maternal hyperthermia) and maternal metabolic conditions. Proving the teratogenicity of a factor is a difficult task requiring epidemiology studies as well as experimental teratology evidence from the use of animal models, one of which is the chicken embryo. This model in particular has the advantage of being able to follow development live and in vivo, with rapid development hatching around 21 days, is cheap and easy to manipulate and to observe development. All this allows the chicken embryo to be used in drug screening studies, teratogenic evaluation and studies of mechanisms of teratogenicity. The chicken embryo shares morphological, biochemical and genetic similarities with humans as well as mammalian species, making them ideal to ascertain the actions of teratogens, as well as screen drugs to test for their safety. Pre-clinical trials for new drugs are carried out in rodents and rabbits, however, chicken embryos have been used to screen new compounds or analogs of thalidomide as well as to investigate how some drugs can lead to congenital malformations. Indeed, the chicken embryo has proved valuable in understanding how many congenital anomalies, seen in humans, arise following teratogen exposure. The aim of this review is to highlight the role of the chicken embryo as an experimental model for studies in teratology, exploring its use in drug screening studies, phenotypic evaluation and studies of teratogenic mechanisms of action. Here, we discuss many known teratogens, that have been evaluated using the chicken embryo model including some medicines, such as, thalidomide, valproic acid; recreational drugs including alcohol; environmental influences, such as viruses, specifically ZIKV, which is a newly discovered human teratogen. In addition, we discuss how the chicken embryo has provided insight on the mechanisms of teratogenesis of many compounds and also how this impact on drug safety