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Introdução: Desde 2022, foi identificado surto multinacional da mpox, infecção causada pelo Monkeypoxvirus (MPXV). O Brasil apresentou inúmeros casos, com 11.212 confirmados até 30/01/2024, afetando desproporcionalmente homens que fazem sexo com homens (HSH). A evolução clínica da mpox cursa geralmente com síndrome febril aguda e lesões mucocutâneas. Geralmente tem evolução autolimitada, mas pode complicar com infecção secundária e acometimento de tecidos profundos. A transmissão por contato sexual foi mais descrita no surto de 2022/2023, podendo ocorrer pelo contato direto ou indireto com lesões, fluidos corporais e gotículas respiratórias de pessoas com mpox. Relato de caso: Mulher cisgênero, 28 anos, com epilepsia controlada, sem outras comorbidades, trabalha como vendedora em praça pública, internada em 04/2024 em unidade hospitalar externa devido à lesão pustular fronto-temporal direita, evolução de 2 dias, que progrediu com sinais de infecção secundária e celulite periorbitária. Esta regrediu completamente com antibioticoterapia, porém houve progressão da lesão primária associada a vesículas em dedos e região perianal. Aventada hipótese de mpox, foi transferida para este centro, onde se observou lesão vegetante e crostosa em fronte, duas lesões vesiculares em região metacarpofalangeana e uma em região interfalangeana distal, além de lesão em linha média torácica e outra em região perianal, ambas de centro ulcerado e indolores. A paciente negou contato com pessoas com quadro semelhante e exposição sexual nos últimos 3 anos. O rastreio infeccioso foi negativo para infecções fúngicas e ISTs. PCR MPXV foi detectável em swabs coletados em todas as lesões e PCR para varicela zoster foi não detectável. Recebeu suporte clínico e orientações de isolamento domiciliar e encaminhada para seguimento ambulatorial. Comentários: O relato aponta diagnóstico de mpox em mulher cis, com lesão inicial extragenital, sem contato sexual e provável aquisição comunitária (já que trabalha em praça pública). Desde 10/2023, o Rio de Janeiro apresenta transmissão sustentada de mpox, e profissionais de saúde precisam estar atentos para evoluções atípicas e oligossintomáticas, possibilitando identificação e diagnóstico adequados. Medidas de prevenção, como campanhas de vacinação, precisam ser implementadas sobretudo para as populações mais vulnerabilizadas. Palavras-chave: Mpox, Transmissão, Comunitária. Conflitos de interesse: Informo que não possuo conflitos de interesses relacionados a este trabalho. Ética e financiamentos: Declarações de interesse: nenhuma. Declarações de interesse: Nenhum.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2–8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17–36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0–7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Abstract Despite the key role of fibrosis in atrial fibrillation (AF), the effects of different spatial distributions and textures of fibrosis on wave propagation mechanisms in AF are not fully understood. To clarify these aspects, we performed a systematic computational study to assess fibrosis effects on the characteristics and stability of re-entrant waves in electrically-remodelled atrial tissues. A stochastic algorithm, which generated fibrotic distributions with controlled overall amount, average size, and orientation of fibrosis elements, was implemented on a monolayer spheric atrial model. 245 simulations were run at changing fibrosis parameters. The emerging propagation patterns were quantified in terms of rate, regularity, and coupling by frequency-domain analysis of correspondent synthetic bipolar electrograms. At the increase of fibrosis amount, the rate of reentrant waves significantly decreased and higher levels of regularity and coupling were observed (p

Recent data shows that alterations in the expression and/or activation of the vascular endothelial growth factor receptor 2 (VEGFR2) in high grade serous ovarian cancer (HGSOC) modulate tumor progression. However, controversial results have been obtained, showing that in some cases VEGFR2 inhibition can promote tumorigenesis and metastasis. Thus, it is urgent to better define the role of the VEGF/VEGFR2 system to understand/predict the effects of its inhibitors administered as anti-angiogenic in HGSOC. Here, we modulated the expression levels of VEGFR2 and analyzed the effects in two cellular models of HGSOC. VEGFR2 silencing (or its pharmacological inhibition) promote the growth and invasive potential of OVCAR3 cells in vitro and in vivo. Consistent with this, the low levels of VEGFR2 in OV7 cells are associated with more pronounced proliferative and motile phenotypes when compared to OVCAR3 cells, and VEGFR2 overexpression in OV7 cells inhibits cell growth. In vitro data confirmed that VEGFR2 silencing in OVCAR3 cells favors the acquisition of an invasive phenotype by loosening cell-ECM contacts, reducing the size and the signaling of focal adhesion contacts (FAs). This is translated into a reduced FAK activity at FAs, ECM-dependent alterations of mechanical forces through FAs and YAP nuclear translocation. Together, the data show that low expression, silencing or inhibition of VEGFR2 in HGSOC cells alter mechanotransduction and lead to the acquisition of a pro-proliferative/invasive phenotype which explains the need for a more cautious use of anti-VEGFR2 drugs in ovarian cancer.

Objective: In 2019 the Dutch national prevention of preterm birth (PTB) protocol was adjusted to withhold tocolysis for threatened PTB above 30 weeks of gestation due to insufficient evidence regarding its effectiveness on improving perinatal outcomes. The aim of this study is to evaluate neonatal outcomes of children born in the Netherlands between 30 and 32 weeks of gestation before and after the national protocol change. Study design: We performed a nationwide retrospective cohort study comparing outcomes of births in the years 2018 (tocolysis) and 2020 (no tocolysis). Tocolytic therapy consisted of either nifedipine or atosiban. Data were extracted from the national Perinatal Registry (PERINED). Women with a spontaneous PTB from 30 + 0 to 31 + 6 weeks of gestation were included. The primary outcome was a composite of mortality, severe intraventricular hemorrhage, severe necrotizing enterocolitis, cystic periventricular leukomalacia, and retinopathy of prematurity needing therapy. Secondary outcomes included additional neonatal outcomes. The odds ratio (OR) with corresponding 95 % confidence interval (CI) was calculated by logistic regression analysis for the year 2020 compared with 2018. Results: Composite neonatal outcome did not differ between 2018 compared to 2020 (8.4 % (18/215) vs 8.2 % (25/306), OR 0.95; 95 % CI 0.51–1.77). No difference in composite neonatal outcome was found when analyzing groups as singletons (7.1 % vs 9.3 %, OR 1.35; 95 % CI 0.64–2.87), and multiples (13.3 % vs 5.9 %, OR 0.41; 95 % CI 0.13–1.26). Conclusion: There was no significant difference in composite neonatal outcome in pregnancies resulting in spontaneous PTB between 30 and 32 weeks of gestation in 2018 (with tocolysis) compared to 2020 (no tocolysis). These results support the protocol adjustment to withhold tocolytic treatment in women with threatened PTB above 30 weeks of gestation.

Background and objectives: Anorexia of aging (AoA) is a prevalent geriatric syndrome characterized by a multifactorial decline in appetite and reduced food intake associated with the aging process. This systematic review aims to investigate the use and outcomes of cannabinoids in addressing AoA, with the goal of providing a comprehensive understanding and discussing their potential integration into daily clinical practice. Methods: A thorough search of databases (Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science) identified 6100 studies. After eliminating duplicates and screening titles and abstracts, 25 studies underwent full appraisal. Two reviewers assessed inclusion suitability, and study methodologies were evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the modified Jadad Scoring Scale for randomized controlled trials. Ultimately, six studies published between 2002 and 2019, involving 869 participants, were included in the review. Results: Out of the 6 fin. l papers selected, 5 were randomized trials, and 1 was a prospective study. Megestrol acetate (800 mg/d) proved to be more effective than dronabinol 2.5 mg twice a day in increasing appetite. Nabilone (at a dosage of 0.5 mg per day) did not show superiority over placebo in alleviating symptoms such as pain, nausea, loss of appetite, and weight. However, with a double dosage followed by 1.0 mg/6 weeks, after eight weeks of treatment, patients recorded a significant increase in calorie intake and carbohydrate consumption compared to the placebo group, with some patients also experiencing substantial weight gain. Regarding delta-9-tetrahydrocannabinol (THC), a weight increase of ≥10% was observed in 17.6% of patients with doses of 5 mg or 10 mg capsules daily, without significant side effects. Additionally, patients treated with THC 2.5 mg reported improved chemosensory perception and increased appetite before meals compared to placebo. No significant side effects were reported in older adults taking cannabinoids. Conclusions: Cannabinoids offer promise in enhancing the quality of life for older individuals with active neoplastic disease. However, to establish comprehensive guidelines, further research with larger sample sizes is essential. Only through this approach can we fully grasp the potential and application of cannabinoids in addressing the nutritional concerns associated with neoplastic diseases.

ABSTRACT Proteins encoded by the ESX-1 genes of interest are essential for full virulence in all Mycobacterium tuberculosis complex (Mtbc) lineages, the pathogens causing the highest mortality worldwide. Identifying critical regions in these ESX-1-related proteins could provide preventive or therapeutic targets for Mtb infection, the game changer needed for tuberculosis control. We analyzed a compendium of whole genome sequences of clinical Mtb isolates from all lineages from >32,000 patients and identified single nucleotide polymorphisms. When mutations corresponding to all non-synonymous single nucleotide polymorphisms were mapped on structural models of the ESX-1 proteins, fully conserved regions emerged. Some could be assigned to known quaternary structures, whereas others could be predicted to be involved in yet-to-be-discovered interactions. Some mutants had clonally expanded (found in >1% of the isolates); these mutants were mostly located at the surface of globular domains, remote from known intra- and inter-molecular protein–protein interactions. Fully conserved intrinsically disordered regions of proteins were found, suggesting that these regions are crucial for the pathogenicity of the Mtbc. Altogether, our findings highlight fully conserved regions of proteins as attractive vaccine antigens and drug targets to control Mtb virulence. Extending this approach to the whole Mtb genome as well as other microorganisms will enhance vaccine development for various pathogens.IMPORTANCEWe mapped all non-synonymous single nucleotide polymorphisms onto each of the experimental and predicted ESX-1 proteins’ structural models and inspected their placement. Varying sizes of conserved regions were found. Next, we analyzed predicted intrinsically disordered regions within our set of proteins, finding two putative long stretches that are fully conserved, and discussed their potential essential role in immunological recognition. Combined, our findings highlight new targets for interfering with Mycobacterium tuberculosis complex virulence.

Objetivo: Descrever o processo de construção do material didático “Meu plano de aleitamento materno” para educação, apoio e promoção do aleitamento materno para gestantes e pessoas lactantes. Método: Este é um estudo metodológico realizado em três fases: diagnóstico situacional, revisão de literatura e contextualização da prática profissional, e construção da tecnologia educacional baseada em políticas públicas e programas de aleitamento materno brasileiros. O estudo ocorreu de março de 2022 a outubro de 2023 e utilizou-se o software Canva para construção do produto. Resultados: Desenvolveu-se uma tecnologia inédita a nível nacional que integra educação e cuidado em saúde por meio do plano de aleitamento materno. Considerações finais: Considera-se que o material didático intitulado “Meu plano de aleitamento materno” é um recurso eficaz para promover a autonomia da mulher no ciclo gravídico-puerperal e pode ser utilizado na enfermagem para educar, promover e apoiar o aleitamento materno em diversos níveis de atenção à saúde.

BackgroundFederated learning (FL) is a technique for learning prediction models without sharing records between hospitals. Compared to centralized training approaches, the adoption of FL could negatively impact model performance.AimThis study aimed to evaluate four types of multicenter model development strategies for predicting 30-day mortality for patients undergoing transcatheter aortic valve implantation (TAVI): (1) central, learning one model from a centralized dataset of all hospitals; (2) local, learning one model per hospital; (3) federated averaging (FedAvg), averaging of local model coefficients; and (4) ensemble, aggregating local model predictions.MethodsData from all 16 Dutch TAVI hospitals from 2013 to 2021 in the Netherlands Heart Registration (NHR) were used. All approaches were internally validated. For the central and federated approaches, external geographic validation was also performed. Predictive performance in terms of discrimination [the area under the ROC curve (AUC-ROC, hereafter referred to as AUC)] and calibration (intercept and slope, and calibration graph) was measured.ResultsThe dataset comprised 16,661 TAVI records with a 30-day mortality rate of 3.4%. In internal validation the AUCs of central, local, FedAvg, and ensemble models were 0.68, 0.65, 0.67, and 0.67, respectively. The central and local models were miscalibrated by slope, while the FedAvg and ensemble models were miscalibrated by intercept. During external geographic validation, central, FedAvg, and ensemble all achieved a mean AUC of 0.68. Miscalibration was observed for the central, FedAvg, and ensemble models in 44%, 44%, and 38% of the hospitals, respectively.ConclusionCompared to centralized training approaches, FL techniques such as FedAvg and ensemble demonstrated comparable AUC and calibration. The use of FL techniques should be considered a viable option for clinical prediction model development.

BackgroundObesity prevalence in youth with spina bifida is higher than in their typically developing peers. Obesity is associated with lifelong medical, psychological, and economic burdens. Successful prevention or treatment of obesity in individuals with spina bifida is compromised by (1) the lack of valid and reliable methods to identify body fat in a clinical setting and (2) limited data on energy expenditure that are necessary to provide daily caloric recommendations. ObjectiveThe objectives of this study will be to develop 2 algorithms for use in youth with spina bifida in a clinical setting, one to model body fat and one to predict total daily energy expenditure. In addition, physical activity and dietary intake will be described for the sample. MethodsThis multisite, prospective, national clinical study will enroll 232 youth with myelomeningocele aged 5 to 18 years (stratified by age and mobility). Participants will be enrolled for 1 week. Data obtained include 4 measures of body composition, up to 5 height measures, a ramped activity protocol, and a nutrition and physical activity screener. Participants will wear an accelerometer for the week. On the final study day, 2 samples of urine or saliva, which complete the doubly labeled water protocol, will be obtained. The analysis will include descriptive statistics, Bland-Altman plots, concordance correlation, and regression analysis. ResultsThe study received extramural federal funding in July 2019. Data collection was initiated in March 2020. As of April 2024, a total of 143 (female participants: n=76, 53.1%; male participants: n=67, 46.9%) out of 232 participants have been enrolled. Data collection is expected to continue throughout 2024. A no-cost extension until November 2025 will be requested for data analysis and dissemination of findings. ConclusionsThis study furthers previous pilot work that confirmed the acceptability and feasibility of obtaining alternate height, body composition, and energy expenditure measures. The findings from this study will enhance screening, prevention, and treatment of abnormal weight status by facilitating the accurate identification of youths’ weight status category and recommendations of daily caloric needs for this population that is at higher risk of obesity. Furthermore, the findings have the potential to impact outcomes for youth diagnosed with disabilities other than spina bifida who experience similar challenges related to alterations in body composition or fat distribution or measurement challenges secondary to mobility issues or musculoskeletal problems. International Registered Report Identifier (IRRID)DERR1-10.2196/52779

BackgroundGNAO1-related disorders (GNAO1-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1-RD.ObjectivesThis study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies.MethodsA Delphi consensus process was conducted involving international experts in GNAO1-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise.ResultsConsensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis.ConclusionThis consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1-RD research.

During COVID-19 pandemic pediatricians have been challenged by the occurrence of the multisystem inflammatory syndrome in children (MIS-C). This condition displays some features similar to those of Kawasaki disease (KD), but was is characterized by clinical signs and symptoms that are infrequent in this illness, such as diarrhea, abdominal pain, neurologic dysfunction and cardiac involvement, especially myocarditis. Many children with MIS-C necessitated ICU admission due to development of multiorgan failure and circulatory shock, usually of myocardial origin. Management is based on the administration of intravenous immunoglobulin, glucocorticoids and, in the most severe forms, anakinra. The clinical similarities between MIS-C and KD have raised an intense debate about whether they represent different illnesses with overlapping clinical features or are part of the same disease spectrum. Most authorities favor the assumption that MIS-C is distinct from KD, based on epidemiological, clinical and immunological differences between the two entities. Others argue that the two disorders may represent a continuum, with some differences in phenotype and severity being related to viral load or strain or magnitude or kinetics of immune response. The present article is aimed to analyze critically the rationale and evidence in favor of the second hypothesis.

A presente pesquisa tem por objetivo principal discutir a atuação profissional e educativa com pessoas idosas na Educação de Jovens e Adultos (EJA) em favor dos interesses das classes populares. De modo específico, caracterizar a sociedade contemporânea e o processo formativo de pessoas idosas que estudam ou estudaram na EJA à luz dos conceitos de cidadania e humanização, principalmente por considerar que na sociedade capitalista há um processo que caminha para a formação desumana, desigual e preconceituosa. Há, ainda, a situação permeada por sentimentos de angústia diante o “fracasso escolar”, consideravelmente no que tange o processo de rompimento das barreiras para “vencer” o “cotidiano” que impõe toda a espécie de obstáculos e estigmatizações. Por este motivo, faz-se necessária a intervenção do Estado, primeiramente, com políticas educacionais capazes de proporcionar uma vida digna a todos, de forma a promover o acesso a uma educação inclusiva, a partir da relação estabelecida entre equipe escolar e educandos, de maneira efetiva à luz dos direitos sobre os educandos, conforme previsto na Constituição Federal (1988), na Lei de Diretrizes e Bases da Educação (1996), no Estatuto da Pessoa Idosa, e na Declaração dos Direitos Humanos.

Abstract Introduction Much has been written and spoken about telemedicine since about two decades including an article in this journal at the start of the pandemic. It took a global catastrophe to enforce its usage across the world in various medical specialties. Telemedicine however remains unstructured, unregulated and lacks uniformity. Discussion This article highlights the practical learnings and opinions of the authors who provided over two thousand video consults and asynchronous telemedicine services through the entire pandemic. It includes lessons learnt from emerging economies where pediatric rheumatologists are scarce. Pediatric rheumatology, which relies heavily on history, musculoskeletal and skin examination is aptly suited to exploit telemedicine in its synchronous and asynchronous forms. Pediatric tele rheumatology could temporarily address the shortage and uneven distribution of specialists in vast parts of the globe, besides serving as a method of triage and shared care with the primary physician. Reduction of direct and indirect costs and family/primary physician education are additional benefits. There also exist challenges for all stakeholders and it is important to address the latter. Conclusion The learnings of the pandemic suggest a vital role for telemedicine in the practice of pediatric rheumatology. This is a fertile area for research and consensus building by international and national pediatric societies and issue position statements like some adult bodies already have. The authors speculate a hybrid system of care in the not-so-distant future.

The literature on COVID-19 continues to increase daily. Cognitive sequelae associated with COVID-19 infection still draw the attention of the scientific community given the lack of consensus about their existence, etiology, characterization and reversibility. The aim of this study is to provide a neuropsychological identikit for younger (

O presente artigo tem por sustentação a reflexão acerca de elementos políticos presentes no texto dramático Bodas de café, produzido pela autora londrinense Nitis Jacon, em 1984. O ponto de partida para a reflexão sobre a peça é a teoria do teatro épico do dramaturgo alemão Bertolt Brecht, o qual se opõe ao teatro dramático, propondo a reflexão crítica por parte do espectador. Dessa forma o objetivo primário da pesquisa é promover uma reflexão das relações humanas com seu meio social no texto dramático, a trajetória do homem e suas transformações. E os objetivos secundários são destacar o trabalho de dramaturgia londrinense, que ainda é pouco pesquisado, e por fim, também contribuir para novas pesquisas acerca do tema dramaturgia londrinense. A pesquisa resgata uma grande época do teatro londrinense, em que se produzia e encenava textos teatrais com uma linguagem própria. Tanto o grupo PROTEU quanto a autora Nitis Jacon fizeram história e abriram caminhos para que Londrina se tornasse esse grande polo cultural e que ainda é pouco conhecido. E nela também enfatizamos a importância da liberdade com príncípio fundamental dos direitos humanos e educacionais.

RESUMO Com o objetivo de avaliar a adsorção e a lixiviação do herbicida chlorsulfuron, foram realizados ensaios em colunas de solo com amostras de Latossolos durante o ano de 1995. Para a avaliação da lixiviação foram utilizadas amostras do horizonte superficial (A) e para a adsorção amostras dos horizontes superficial e subperficial (B). Os resultados demonstraram uma elevada adsorção (Kd = 0,94 a 16,00 dm3 kg-1), atribuível ao alto conteúdo de matéria orgânica e a presença de óxidos de Fe e Al. A maior lixiviação do herbicida ocorreu nas amostras com menor poder de adsorção, demonstrando que, para solos tropicais, a mobilidade do chlorsulfuron apresenta comportamento similar ao observado nos solos de clima temperado.

RESUMO O estudo objetivou compreender a atenção pré-natal em uma região de fronteira na vigência da pandemia da Covid-19. Trata-se de um estudo qualitativo, realizado em serviços da atenção primária à saúde, com 27 participantes, entre mulheres e profissionais de saúde, por meio de entrevistas semiestruturadas, remotas e presenciais, entre agosto de 2021 e janeiro de 2022, cujos dados foram averiguados por análise temática. Foram identificadas quatro categorias temáticas, quais sejam: Início do pré-natal adiado; Parcialidade nas ações em saúde no pré-natal; (Des)informação em saúde em período de pandemia; e Medidas de prevenção à Covid-19 na gestação. A pandemia da Covid-19 gerou retrocessos no pré-natal, como a restrição do acompanhante nas consultas e exames e suspensão de grupos de gestantes, com prejuízos na educação em saúde, adiamento do início do pré-natal e/ou comprometimento da sua realização, particularmente de brasileiras residentes no Paraguai. Teleatendimento, como estratégia para acompanhamento do pré-natal, apareceu timidamente. Os serviços de saúde se reorganizaram para manter as medidas para evitar a infecção e, assim, tentar garantir o seguimento pré-natal de forma presencial.

Background: Recently, the substitution R1051Q in VEGFR2 has been described as a cancer-associated “gain of function” mutation. VEGFR2R1051Q phosphorylation is ligand-independent and enhances the activation of intracellular pathways and cell growth both in vitro and in vivo. In cancer, this mutation is found in heterozygosity, suggesting that an interaction between VEGFR2R1051Q and VEGFR2WT may occur and could explain, at least in part, how VEGFR2R1051Q acts to promote VEGFR2 signaling. Despite this, the biochemical/biophysical mechanism of the activation of VEGFR2R1051Q remains poorly understood. On these bases, the aim of our study is to address how VEGFR2R1051Q influences the biophysical behavior (dimerization and membrane dynamics) of the co-expressed VEGFR2WT. Methods: We employed quantitative FLIM/FRET and FRAP imaging techniques using CHO cells co-transfected with the two forms of VEGFR2 to mimic heterozygosity. Results: Membrane protein biotinylation reveals that VEGFR2WT is more exposed on the cell membrane with respect to VEGFR2R1051Q. The imaging analyses show the ability of VEGFR2WT to form heterodimers with VEGFR2R1051Q and this interaction alters its membrane dynamics. Indeed, when the co-expression of VEGFR2WT/VEGFR2R1051Q occurs, VEGFR2WT shows reduced lateral motility and a minor pool of mobile fraction. Conclusions: This study demonstrates that active VEGFR2R1051Q can affect the membrane behavior of the VEGFR2WT.

Leucine-rich repeat kinase-2 (LRRK2), a gene mutated in familial and sporadic Parkinson’s disease (PD), controls multiple cellular processes important for GLIA physiology. Interestingly, emerging studies report that LRRK2 is highly expressed in oligodendrocyte precursor cells (OPCs) compared to the pathophysiology of other brain cells and oligodendrocytes (OLs) in PD. Altogether, these observations suggest crucial function(s) of LRRK2 in OPCs/Ols, which would be interesting to explore. In this study, we investigated the role of LRRK2 in OLs. We showed that LRRK2 knock-out (KO) OPC cultures displayed defects in the transition of OPCs into OLs, suggesting a role of LRRK2 in OL differentiation. Consistently, we found an alteration of myelin basic protein (MBP) striosomes in LRRK2 KO mouse brains and reduced levels of oligodendrocyte transcription factor 2 (Olig2) and Mbp in olig2:EGFP and mbp:RFP transgenic zebrafish embryos injected with lrrk2 morpholino (MO). Moreover, lrrk2 knock-down zebrafish exhibited a lower amount of nerve growth factor (Ngf) compared to control embryos, which represents a potent regulator of oligodendrogenesis and myelination. Overall, our findings indicate that LRRK2 controls OL differentiation, affecting the number of mature OLs.

In order to reduce greenhouse gas emissions associated with power generation, the replacement of fossil fuels with renewables must be accompanied by the availability of dispatchable sources needed to balance electricity demand and production. Combined cycle (CC) power plants adopting post-combustion capture (PCC) can serve this purpose, ensuring near-zero CO2 emissions at the stack, as well as high efficiency and load flexibility. In particular, the chemical absorption process is the most established approach for industrial-scale applications, although widespread implementation is lacking. In this study, different natural gas combined cycle (NGCC) configurations were modeled to estimate the burden of retrofitting the capture process to existing power plants on thermodynamic performance. Simulations under steady-state conditions covered the widest possible load range, depending on the gas turbine (GT) model. Attention was paid to the net power loss and net efficiency penalty attributable to PCC. The former can be mitigated by lowering the GT air–fuel ratio to increase the CO2 concentration (XCO2) in the exhaust, thus decreasing the regeneration energy. The latter is reduced when the topping cycle is more efficient than the bottoming cycle for a given GT load. This is likely to be the case in the less-complex heat recovery units.

Objectives To develop and validate the cut-offs in the Juvenile DermatoMyositis Activity Index (JDMAI) to distinguish the states of inactive disease (ID), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) in children with juvenile dermatomyositis (JDM).Methods For cut-off definition, data from 139 patients included in a randomised clinical trial were used. Among the six versions of the JDMAI, JDMA1 (score range 0–40) and JDMAI2 (score range 0–39) were selected. Optimal cut-offs were determined against external criteria by calculating different percentiles of score distribution and through receiver operating characteristic curve analysis. External criteria included the modified Pediatric Rheumatology International Trials Organization (PRINTO) criteria for clinically ID in JDM (for ID) and PRINTO levels of improvement in the clinical trial (for LDA and HDA). MDA cut-offs were set at the score interval between LDA and HDA cut-offs. Cut-off validation was conducted by assessing construct and discriminative ability in two cohorts including a total of 488 JDM patients.Results The calculated JDMAI1 cut-offs were ≤2.4 for ID, ≤6.6 for LDA, 6.7–11 for MDA and >11 for HDA. The calculated JDMAI2 cut-offs were ≤5.2 for ID, ≤8.5 for LDA, 8.6–11.3 for MDA and >11.3 for HDA. The cut-offs discriminated strongly among disease activity states defined subjectively by caring physicians and parents, parents’ satisfaction or non-satisfaction with illness outcome, levels of pain, fatigue, physical functional impairment and physical well-being.Conclusions Both JDMAI1 and JDMAI2 cut-offs revealed good metrologic properties in validation analyses and are, therefore, suited for application in clinical practice and research.

[This corrects the article DOI: 10.1371/journal.pone.0304172.].