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In several urban and peri‑urban areas of Brazil, populations of Amblyomma sculptum and Amblyomma dubitatum ticks are maintained by capybaras (Hydrochoerus hydrochaeris). In some of these areas, this host and these tick species are associated with Brazilian spotted fever (BSF), a lethal human disease caused by the bacterium Rickettsia rickettsii. In this work, we evaluated the risk of human exposure to these tick species using four collection techniques to discern host-seeking behavior. The study was carried out in 10 urban sites inhabited by capybaras in Uberlândia, a BSF-free municipality in southeastern Brazil. Ticks were collected in areas of 400 m2 at each site and at three seasons. Within the same municipality, the distance and speed of A. sculptum nymphs moving towards the CO2 traps were evaluated. In a sample of ticks Rickettsia DNA was investigated. During the study period, 52,953 ticks were collected. Among these, 83.4 % were A. sculptum (1,523 adults, 10,545 nymphs and 32,104 larvae) and 16.6 % were A. dubitatum (464 adults, 2,153 nymphs and 6,164 larvae). An average annual questing tick density of 4.4/m² was observed, with the highest density recorded at one site in autumn (31.8/m²) and the lowest in summer at another site (0.03/m²). The visual search yielded the highest proportion of A. sculptum larvae, constituting 47 % of the total and 63.6 % of all A. sculptum larvae. In contrast, CO2 traps collected a greater proportion of nymphs and adults of A. sculptum ticks. In the case of A. dubitatum, the CO2 trap was the most efficient technique with 57.7 % of captures of this species, especially of nymphs (94.5 % of captures) and adults (97.8 % of captures). Ticks' ambush height on vegetation (9 to 77 cm), observed by visual search 30 times, yielded a total of 20,771 ticks. Of these, 28 (93 %) were A. sculptum ticks, with only two (7 %) identified as A. dubitatum ticks. Among A. sculptum ticks, the nymph was the most attracted stage to humans and larva in the case of A. dubitatum. Amblyomma sculptum adults and nymphs were significantly more attracted to humans than those of A. dubitatum, but A. dubitatum larvae were significantly more attracted than the same stage of A. sculptum. The maximum distance and speed of horizontal displacement for A. sculptum nymphs were five meters and 2.0 m/h, respectively. The only species of Rickettsia detected in ticks, exclusively in A. dubitatum, was R. bellii. Importantly, it was observed that the higher the proportion of A. sculptum in the community of ticks, the lower the rate of infection of A. dubitatum by R. bellii. In conclusion, host-seeking behavior differed between the two tick species, as well as between stages of the same species. A greater restriction of A. dubitatum ticks to the soil was observed, while larvae and nymphs of A. sculptum dispersed higher in the vegetation. The behavior presented by A. sculptum provides greater opportunities for contact with the hosts, while A. dubitatum depends more on an active search for a host, the hunter behavior. Taken together, these observations show that a human being crossing an area infested with A. sculptum and A. dubitatum ticks will have almost exclusive contact with A. sculptum larvae and/or nymphs. Humans in a stationary position (sitting, lying or immobile) are exposed to both tick species, but they are more attractive to adults and mainly nymphs of A. sculptum compared to the corresponding stages of the tick A. dubitatum. The negative effect of A. sculptum on A. dubitatum infection by R. bellii deserves further studies.

Este trabalho busca compreender o conceito de formação como temática central da filosofia da educação. A questão que enreda a análise proposta é: Em que bases a formação pode ser conceituada? O problema posto delimita o seguinte objetivo deste estudo: analisar o conceito de formação na perspectiva filosófica de Hegel, Kant e Dewey para compreender sua relação com a educação. A metodologia da pesquisa é de caráter bibliográfico e consiste em analisar o conceito de formação na no pensamento de Hegel, Kant e Dewey. Como resultado, a pesquisa problematiza a concepção de formação do ser humano como subsidiária do conteúdo da filosofia na perspectiva de Hegel assemelhada a viagem e conhecimento. Indaga também a formação humana como filosofar sem o conteúdo filosófico acabado, como êxodo dos tutoramentos. Apresenta a alternativa de Dewey que aponta a dimensão conflituosa e problemática na contingência da situação como motor que move o pensamento e que move a vida e que este autor tematiza no conceito de experiência lastreado no princípio de continuidade e interação, reconstrução e crescimento. Filosofar é mergulhar na experiência, estar molhado da sua materialidade e imaterialidade histórica, social e cultural. A formação adquire o sentido de formagir educativo e democrático. .

Objetivo: Este estudo teve como objetivo avaliar os fatores do ambiente alimentar escolar associados à adesão à alimentação escolar entre adolescentes de escolas públicas brasileiras. Métodos: Trata-se de um estudo transversal com dados de 67.881 adolescentes de 11 a 19 anos, estudantes de escolas públicas que participaram da Pesquisa Nacional de Saúde do Escolar (PeNSE) 2015. A variável dependente foi a frequência de consumo da alimentação escolar, classificada em adesão (≥3x/semana), adesão insatisfatória (1-2x/semana) e não adesão (nenhum dia). Utilizou-se regressão multinível ordinal para estimar o efeito das variáveis individuais e do ambiente escolar na adesão à alimentação escolar. Resultados: Dentre os estudantes avaliados, 31,3% aderiram à alimentação escolar, 37,9% aderiram insatisfatoriamente e 30,8% não aderiram. Após ajuste para variáveis individuais, observou-se maior adesão entre os que frequentavam escolas sem cantina (OR: 1,46; IC 95%: 1,35-1,57), sem ponto alternativo de venda de alimentos (OR: 1,29; IC 95%: 1,20-1,39 ), do Sul (OR: 1,38; IC 95%: 1,22-1,56), Sudeste (OR: 1,30; IC 95%: 1,16-1,46) e Centro-Oeste (OR: 1,95; IC 95%: 1,75-2,18) , não capitais (OR: 1,42; IC 95%: 1,33-1,52) e áreas rurais (OR: 1,41; IC 95%: 1,26-1,57). Conclusão: Os estudantes que frequentam escolas sem cantina e ponto alternativo de venda apresentaram 46% e 29% maiores chances de adesão à alimentação escolar, respectivamente. Esses resultados destacam a necessidade de intervenções que promovam um ambiente escolar alimentar mais saudável e fortaleçam as ações de Educação Alimentar e Nutricional nas escolas públicas brasileiras.

IntroductionAbout 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR). RTKs inhibitors have not clearly demonstrated anti-tumor activity in BRAFi resistant models. To overcome this issue, we wondered whether the shared up-regulated RTK phenotype associated with BRAFi resistance could be exploited by using immune weapons as the antibody-dependent cell cytotoxicity (ADCC)-mediated effect of anti-RTKs antibodies, and kill tumor cells independently from the mechanistic roots.Methods and resultsBy using an in vitro model of BRAFi resistance, we detected increased membrane expression of EGFR, both at mRNA and protein level in 4 out of 9 BRAFi-resistant (VR) CM cultures as compared to their parental sensitive cells. Increased EGFR phosphorylation and AKT activation were observed in the VR CM cultures. EGFR signaling appeared dispensable for maintaining resistance, since small molecule-, antibody- and CRISPR-targeting of EGFR did not restore sensitivity of VR cells to BRAFi. Importantly, immune-targeting of EGFR by the anti-EGFR antibody cetuximab efficiently and specifically killed EGFR-expressing VR CM cells, both in vitro and in humanized mouse models in vivo, triggering ADCC by healthy donors’ and patients’ peripheral blood cells. ConclusionOur data demonstrate the efficacy of immune targeting of RTKs expressed by CM relapsing on BRAFi, providing the proof-of-concept supporting the assessment of anti-RTK antibodies in combination therapies in this setting. This strategy might be expected to concomitantly trigger the crosstalk of adaptive immune response leading to a complementing T cell immune rejection of tumors.

Summary: Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

Abstract Background The 2014 estimates of prevalence of food allergy (FA) in Europe published by the European Academy of Allergy and Clinical Immunology included only the eight so‐called big foods (cow's milk/egg/wheat/soy/peanut/tree nuts/fish/shellfish). Those estimates have recently been updated. Complementing this, we sought to identify and estimate the prevalence of allergy to other foods that have been reported during the last decade. Methods Six databases were searched for studies published 2012–2021. Random‐effects meta‐analysis was performed to derive pooled prevalence of allergy to each food. Results Twenty‐seven studies were included, containing a total of 66 FAs. Among the most frequently reported FAs, the lifetime and point prevalence range of self‐reported kiwi allergy was 0.1%–1.0% and 0.2%–8.1%, respectively, while the food challenge (FC)‐verified kiwi allergy point prevalence range was 0.01%–0.10%. The point prevalence range for self‐reported peach allergy was 0.2%–3.2%, while the range for FC‐verified peach allergy was 0.02%–0.05%. The lifetime and point prevalence range for self‐reported tomato allergy was 0.01%–1.8% and 0.2%–2.1%, respectively. Conclusion Allergy to some foods traditionally not considered important are now emerging as relevant FAs. The focus on FA in Europe should not be limited to the so‐called eight big FA, but extended to other types of foods which need to be considered both for clinical purposes and population risk assessment.

Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model.Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data.Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained.Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.

A síndrome pós-COVID-19 é um termo usado para descrever um conjunto diversificado de sintomas que persistem por mais de 12 semanas da infecção diagnosticada. O objetivo deste estudo foi analisar a síndrome pós-COVID-19 entre hospitalizados por COVID-19 após 6 e 12 meses da alta hospitalar. Trata-se de estudo de coorte ambidirecional, realizado com indivíduos que receberam alta em três dos principais hospitais da capital de Mato Grosso, Brasil, entre outubro e dezembro de 2021 e janeiro e março de 2022. Após coleta de dados em prontuários, os indivíduos foram entrevistados por telefone após 6 e 12 meses da alta hospitalar, sendo questionados sobre a presença de sintomas persistentes ou novos, para a avaliação de sua frequência segundo características sociodemográficas, econômicas, relativas à internação e condições de saúde. Dos 277 prontuários avaliados, 259 pacientes foram elegíveis para o estudo, 190 aos seis meses e 160 após 12 meses da alta hospitalar. Aos seis meses, 59% eram mulheres, 40% com 60 anos ou mais de idade e 87,4% referiram a presença de pelo menos um sintoma. Aos 12 meses, 58,7% eram mulheres, 37,5% com 30 a 49 anos e 67,5% referiram a presença de pelo menos um sintoma. A fadiga foi o sintoma mais comum após 6 e 12 meses de alta hospitalar (55,3% e 40,6%, respectivamente), seguido de problemas de memória (36,8%; 20%) e perda de cabelo (26,8%; 11,2%). Foi maior a prevalência de síndrome pós-COVID-19 entre indivíduos de maior faixa etária, menor renda, hipertensos, diabéticos e com maior gravidade durante a internação. Os fatores de risco da síndrome pós-COVID-19 contribuem para a compreensão dos efeitos a longo prazo e da importância do acompanhamento após a fase aguda da doença.

Introduction Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, ‘Multiple Sclerosis International Stem Cell Transplant, MIST’, showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS.Methods and analysis StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve ‘no evidence of disease activity’ during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs.Ethics and dissemination The study was approved by the Yorkshire and Humber—Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences.Trial registration number ISRCTN88667898.

Introduction: Charged Particle Therapy plays a key role in the treatment of deep-seated tumours, because of the advantageous energy deposition culminating in the Bragg peak. However, knowledge of the dose delivered in the entrance channel is limited by the lack of data on the beam and fragmentation of the target.Methods: The FOOT experiment has been designed to measure the cross sections of the nuclear fragmentation of projectile and target with two different detectors: an electronic setup for the identification of Z ≥ 3 fragments and a nuclear emulsion spectrometer for Z ≤ 3 fragments. In this paper, we analyze the data taken by exposing four nuclear emulsion spectrometers, with C and C2H4 targets, to 200 MeV/n and 400 MeV/n oxygen beams at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany), and we report the charge identification of produced fragments based on the controlled fading induced on nuclear emulsion films.Results: The goal of identifying fragments as heavy as lithium has been achieved.Discussion: The results will contribute to a better understanding of the nuclear fragmentation process in charged particle therapy and have implications for refining treatment planning in the presence of deep-seated tumors.