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Biodiversity genomics research requires reliable organismal identification, which can be difficult based on morphology alone. DNA-based identification using DNA barcoding can provide confirmation of species identity and resolve taxonomic issues but is rarely used in studies generating reference genomes. Here, we describe the development and implementation of DNA barcoding for the Darwin Tree of Life Project (DToL), which aims to sequence and assemble high quality reference genomes for all eukaryotic species in Britain and Ireland. We present a standardised framework for DNA barcode sequencing and data interpretation that is then adapted for diverse organismal groups. DNA barcoding data from over 12,000 DToL specimens has identified up to 20% of samples requiring additional verification, with 2% of seed plants and 3.5% of animal specimens subsequently having their names changed. We also make recommendations for future developments using new sequencing approaches and streamlined bioinformatic approaches.

Abstract Objective: Shifting from meat-centric to plant-rich diets may help to enable healthier and more sustainable food systems. Here we present the results of a 1-week intervention to promote plant-based eating in a meat-centric food context (i.e. canteen). Design: The intervention included environmental restructuring strategies (e.g. promotional materials and menu redevelopment) and improvements to the offer of plant-based meals. The evaluation (sales data; pre-registered) spanned 3 weeks prior to the intervention (baseline), 1 week during the intervention (immediate/short-term impact) and 3 weeks after the intervention (follow-up). Opinion surveys were also used to collect data with customers during the intervention. Setting: Canteen unit of a university campus in Portugal (Lisbon metropolitan area). Participants: In addition to sales data (baseline: 7965 meals; immediate/short-term: 2635 meals; follow-up: 7135 meals), we used opinion surveys to assess customers’ meal appraisals during the intervention (n = 370). Results: The odds of a sold meal being vegetarian were 24 % higher in the intervention week compared with the pre-intervention period [OR = 1·24, 95 % CI (1·10, 1·40)] and 9 % higher in the post-intervention period compared with the pre-intervention period [OR = 1·09, (95 % CI (1·00, 1·19)]. Survey data showed that vegetarian meals compared favourably to meat and fish alternatives in liking, sustainability and satiety. Conclusions: A short-term, theory-driven, operationally feasible intervention was effective in promoting increased plant-based meal choices in a collective meal context. Nevertheless, these changes were not entirely sustained over time. Future studies could test whether prolonged or more transformative interventions are necessary to unlock entrenched food practices more effectively in meat-centric collective meal contexts.

Introduction: The impact of skin diseases on quality of life varies widely, and some can have an impact similar to that of asthma or cystic fibrosis. Material and methods: We conducted a cross-sectional, observational and descriptive study with the aim of describing the degree to which quality of life was affected in paediatric patients managed in a dermatology clinic by means of the Children’s Dermatology Life Quality Index (CDLQI). Results: In our study, the skin disease with the greatest impact on quality of life was atopic dermatitis, chiefly on account of symptoms like pruritus and insomnia. It was followed by acne, mainly due to the associated negative feelings (shame, sadness, etc.). Quality of life in patients with viral warts and molluscum contagiosum was mostly affected by the treatment, chiefly based on cryotherapy. Most patients with nevi or café-au-lait spots did not have a decreased quality of life, although up to one third of them had negative feelings in relation to their skin disease. Discussion: Atopic dermatitis was the common skin disease that caused the greatest impairment in quality of life in our sample, although other diseases also had an impact on different dimensions of quality of life. We ought to underscore the recommendation to use less painful treatments than cryotherapy for viral warts and molluscum contagiosum, as the impairment in quality of life in paediatric patients with these conditions was mainly due to the treatment. Resumen: Introducción: Las enfermedades cutáneas pueden afectar a la calidad de vida de forma muy variable; el impacto de algunas dermatosis puede ser similar al del asma o la fibrosis quística. Material y métodos: Realizamos un estudio observacional, descriptivo y transversal con el objetivo de describir el grado de afectación de la calidad de vida de los niños que acudieron a la consulta monográfica de Dermatología Pediátrica, mediante el Children’s Dermatology Life Quality Index (CDLQI). Resultados: En este estudio la dermatosis con mayor impacto en la calidad de vida fue la dermatitis atópica, debido principalmente a síntomas como el prurito y el insomnio. El segundo grupo diagnóstico con mayor afectación fue el acné, debido principalmente a los sentimientos negativos (vergüenza, tristeza, etc.) asociados al mismo. Los pacientes con verrugas víricas y moluscos contagiosos tuvieron impacto en la calidad de vida debido principalmente al tratamiento de los mismos, que se realizó principalmente con crioterapia. La mayor parte de los pacientes con nevus o manchas café con leche no tuvieron afectación en la calidad de vida, si bien hasta un tercio de ellos tuvieron sentimientos negativos secundarios a su dermatosis. Discusión: La dermatitis atópica fue la enfermedad dermatológica común que más impactó en la calidad de vida en nuestra muestra de pacientes, aunque otros procesos también afectaron a la calidad de vida en distintos aspectos de la misma. Cabe destacar la recomendación de emplear en verrugas víricas y moluscos contagiosos tratamientos más indoloros que la crioterapia, ya que es el tratamiento lo que más impacta en la calidad de vida de los pacientes pediátricos.

Abstract Microstructural modification of high chromium cast irons (HCCI) through the precipitation of secondary carbides (SC) during destabilization treatments is essential for improving their tribological response. However, there is not a clear consensus about the first stages of the SC precipitation and how both the heating rate (HR) and destabilization temperature can affect the nucleation and growth of SC. The present work shows the microstructural evolution, with a special focus on the SC precipitation, in a HCCI (26 wt% Cr) during heating up to 800, 900, and 980 °C. It was seen that the HR is the most dominant factor influencing the SC precipitation as well as the matrix transformation in the studied experimental conditions. Finally, this work reports for first time in a systematic manner, the precipitation of SC during heating of the HCCI, providing a further understanding on the early stages of the SC precipitation and the associated microstructural modifications.

ABSTRACTMesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

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Background & Aims: In contrast to mismatch repair deficient colorectal carcinoma (CRC), MMR proficient (pMMR) CRC does not respond to immune checkpoint blockade. We studied immune checkpoint stimulation via glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) on ex vivo functionality of human tumor-infiltrating lymphocytes (TIL) isolated from pMMR primary CRC and liver metastases (CRLM). Methods: Using lymphocytes from resected tumor, adjacent tissues, and peripheral blood mononuclear cells (PBMC) of 132 pMMR primary CRC or CRLM patients, we determined GITR expression and the in vitro T-cell agonistic activity of recombinant GITR ligation. Results: Here, we show that GITR was overexpressed on TIL when compared with other stimulatory immune checkpoints (4-1BB, OX40). Its expression was enhanced in TIL compared with PBMC and adjacent tissues. Among CD4+ TIL, GITR expression was primarily expressed by CD45RA- FoxP3hi activated regulatory T cells. Within CD8+ TIL, GITR was predominantly expressed on functionally exhausted and putative tumor-reactive CD103+ CD39+ TIL. Strikingly, recombinant GITRL reinvigorated ex vivo TIL responses by significantly enhancing CD4+ and CD8+ TIL numbers. Dual treatment with GITRL and nivolumab (anti-PD1) enhanced CD8+ TIL expansion compared with GITRL monotherapy. Moreover, GITRL/anti-PD1 dual therapy further improved anti-PD1-mediated reinvigoration of interferon gamma secretion by exhausted CD8 TIL from primary CRC. Conclusions: GITR is overexpressed on CD4+ and CD8+ TIL from pMMR CRC and CRLM. Agonistic targeting of GITR enhances ex vivo human TIL functionality and may therefore be a promising approach for novel monotherapy or combined immunotherapies in primary pMRR CRC and CRLM.

Abstract is missing (Short communication)

Critical thinking is a key competence in higher education. However, little is known about the conception that students have of this competence. This study aims to analyze what university students understand by critical thinking and if these conceptions agree with those of university teachers analyzed in a previous study. A total of 263 participants took part in the study. The findings reveal that students tend to consider critical thinking as a competence related to reasoning/arguing and questioning/asking oneself. Also, that students’ conception about critical thinking differs from that of teachers. Whereas students tend to consider critical thinking as related to reasoning/arguing, questioning/asking oneself and, to a lesser extent, to acting/compromising. Teachers, on the other hand, tend to consider critical thinking as related to analyzing/organizing and evaluating. No significant differences were found regarding students’ gender and academic year. These results highlight the importance of considering students’ views when designing the curricula and the learning activities to develop students’ critical thinking. Received: 30 June 2022 Accepted: 6 March 2023

In the 21st century, critical thinking (CT) is regularly presented as one of the most important competences to be developed by a majority of educational institutions. Teachers are expected to change and enrich their teaching and learning methodologies so that students could face future challenges. Nonetheless, few are the instruments that measure the perception of critical thinking based on teachers’ conception. The aim of this study is to design and validate an instrument for the assessment of CT in university students based on the conception of CT that university teachers have. For this study, a total of 312 Spanish university students have participated. Based on a good model fit from a Confirmatory Factor Analysis and good reliability indices, the results provide strength to the theoretical model to evaluate critical thinking in university students formed by six dimensions (Analyzing/Organizing; Reasoning/Argumenting; Questioning/Asking oneself; Evaluating; Positioning /Taking decisions, and Acting /Committing oneself) and 42 items. Similarly, age was not a predictor variable for the different dimensions; while gender was statistically in favor of women in some of the dimensions, and tendentially, the dimension of Positioning/Taking decisions, in favor of men. However, despite these differences, the model guaranteed its factorial invariance. These findings have important pedagogical implications for universities in particular, and educational institutions in general, when developing curricula and teaching plans that focus on the development of students’ critical thinking.

Current food systems face immediate and complex challenges in feeding a growing global population. It is necessary to mitigate the environmental impact of food systems while ensuring food security across the globe. Drawing on the example of recent multi-sectoral approaches which focus on the interconnections between public health and the environment, this work offers a narrative review and broader conceptual framework advancing two propositions. The first is that school meals systems have the potential to help enable sustainable food transitions. The second is that favoring well-planned plant-based meals in schools may strengthen this potential. The review and resulting framework highlight the relevance of seeking transdisciplinary dialogue and considering diverse sectors of society, such as public health, the environment, social protection, economic development, and community welfare. We review possible health benefits as well as possible economic and environmental outcomes, especially if school meals are sourced mainly from local communities and eco-friendly agricultural practices. Cross-sectoral implications related to social protection and community welfare are also identified and discussed, as well as potential pathways for materializing sustainable food transitions in schools.

Abstract Begonia is an important horticultural plant group, as well as one of the most speciose Angiosperm genera, with over 2000 described species. Genus wide studies of genome size have shown that Begonia has a highly variable genome size, and analysis of paralog pairs has previously suggested that Begonia underwent a whole genome duplication. We address the contribution of gene duplication to the generation of diversity in Begonia using a multi-tissue RNA-seq approach. We chose to focus on chalcone synthase (CHS), a gene family having been shown to be involved in biotic and abiotic stress responses in other plant species, in particular its importance in maximising the use of variable light levels in tropical plants. We used RNA-seq to sample six tissues across two closely related but ecologically and morphologically divergent species, Begonia conchifolia and B. plebeja, yielding 17,012 and 19,969 annotated unigenes respectively. We identified the chalcone synthase gene family members in our Begonia study species, as well as in Hillebrandia sandwicensis, the monotypic sister genus to Begonia, Cucumis sativus, Arabidopsis thaliana, and Zea mays. Phylogenetic analysis suggested the CHS gene family has high duplicate turnover, all members of CHS identified in Begonia arising recently, after the divergence of Begonia and Cucumis. Expression profiles were similar within orthologous pairs, but we saw high inter-ortholog expression variation. Sequence analysis showed relaxed selective constraints on some ortholog pairs, with substitutions at conserved sites. Evidence of pseudogenisation and species specific duplication indicate that lineage specific differences are already beginning to accumulate since the divergence of our study species. We conclude that there is evidence for a role of gene duplication in generating diversity through sequence and expression divergence in Begonia.

Background Despite the worldwide increasing request of education on paediatric musculoskeletal ultrasound (PedMSUS), content, conduct and format of PedMSUS courses have never been internationally agreed.Objectives To produce educational procedures for the conduct, content and format of EULAR/PReS PedMSUS courses.Methods After a systemic literature review and expert opinion collection, a panel of items for the development of procedures on PedMSUS courses was identified. Agreement on the items was assessed through Delphi surveys among a taskforce of 24 members, which included 18 experts in PedMSUS (8 rheumatologists, 1 radiologist, 9 paediatric rheumatologists), 1 methodologist and rheumatologist expert in MSUS, 2 patient research partners, 1 health professional in rheumatology and 2 EMEUNET/EMERGE members, from 8 different European countries. Each item was assessed through a 5-point Likert scale (0, full disagreement; 5, full agreement); agreement was reached for >75% of answers rating 4–5. All items with agreement were included in the preliminary core set of educational procedures, which underwent external assessment by a broader Consensus group (Faculty and Tutors of previous EULAR PedMSUS courses and PReS Imaging Working Party members), through Delphi survey.Results Two Delphi surveys produced the preliminary core set of procedures for basic, intermediate, advanced and teach-the-teachers (TTT) PedMSUS courses. A Delphi survey within the Consensus group produced agreement on the proposed procedures.Conclusions Shared EULAR/PReS procedures for the conduct, content and format of basic, intermediate, advanced and TTT PedMSUS courses were identified on international basis.

We assessed the associations of social distancing and mask use with symptomatic, laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in Porto Alegre, Brazil. We conducted a population-based case-control study during April–June 2020. Municipal authorities furnished case-patients, and controls were taken from representative household surveys. In adjusted logistic regression analyses of 271 case-patients and 1,396 controls, those reporting moderate to greatest adherence to social distancing had 59% (odds ratio [OR] 0.41, 95% CI 0.24–0.70) to 75% (OR 0.25, 95% CI 0.15–0.42) lower odds of infection. Lesser out-of-household exposure (vs. going out every day all day) reduced odds from 52% (OR 0.48, 95% CI 0.29–0.77) to 75% (OR 0.25, 95% CI 0.18–0.36). Mask use reduced odds of infection by 87% (OR 0.13, 95% CI 0.04–0.36). In conclusion, social distancing and mask use while outside the house provided major protection against symptomatic infection.

Objective: To translate the Leuven Knowledge Questionnaire for Congenital Heart Disease into Brazilian Portuguese and to validate its psychometric properties with parents and family caregivers of children with congenital heart disease. Method: This was a six-step methodological study, including the translation, synthesis, back-translation, evaluation of the version translated by the committee of experts, pre-testing, and validation, for which two pilot tests were used including the think-aloud protocol. The content validity index and the frequency of socioeconomic data were calculated in a statistical programming environment. Results: In content validation, the instrument showed good applicability among experts, with average content validity index of 0.8–1, while kappa agreement analysis was between 0.76 to 1; both results were considered adequate for validation. Conclusions: The results suggest reliability among the evaluators, indicating the instrument’s accuracy and the possibility of using it to assess the knowledge of parents and family caregivers about congenital heart disease.

Background & Aims: TIGIT is a co-inhibitory receptor, and its suitability as a target for cancer immunotherapy in HCC is unknown. PD1 blockade is clinically effective in about 20% of advanced HCC patients. Here we aim to determine whether co-blockade of TIGIT/PD1 has added value to restore functionality of HCC tumor-infiltrating T cells (TILs). Methods: Mononuclear leukocytes were isolated from tumors, paired tumor-free liver tissues (TFL) and peripheral blood of HCC patients, and used for flow cytometric phenotyping and functional assays. CD3/CD28 T-cell stimulation and antigen-specific assays were used to study the ex vivo effects of TIGIT/PD1 single or dual blockade on T-cell functions. Results: TIGIT was enriched, whereas its co-stimulatory counterpart CD226 was down-regulated on PD1high CD8+ TILs. PD1high TIGIT+ CD8+ TILs co-expressed exhaustion markers TIM3 and LAG3 and demonstrated higher TOX expression. Furthermore, this subset showed decreased capacity to produce IFN-γ and TNF-α. Expression of TIGIT-ligand CD155 was up-regulated on tumor cells compared with hepatocytes in TFL. Whereas single PD1 blockade preferentially enhanced ex vivo functions of CD8+ TILs from tumors with PD1high CD8+ TILs (high PD1 expressers), co-blockade of TIGIT and PD1 improved proliferation and cytokine production of CD8+ TILs from tumors enriched for PD1int CD8+ TILs (low PD1 expressers). Importantly, ex vivo co-blockade of TIGIT/PD1 improved proliferation, cytokine production, and cytotoxicity of CD8+ TILs compared with single PD1 blockade. Conclusions: Ex vivo, co-blockade of TIGIT/PD1 improves functionality of CD8+ TILs that do not respond to single PD1 blockade. Therefore co-blockade of TIGIT/PD1 could be a promising immune therapeutic strategy for HCC patients.

Resumen: Objetivos: Evaluar el estado psicosocial de los pacientes que acudan a consulta de endocrinología pediátrica por incongruencia de género y determinar el impacto en este sentido de la terapia hormonal cruzada (THC) después de un año. Material y métodos: Se trata de un estudio analítico, prospectivo realizado en adolescentes con incongruencia de género de entre 14 y 18 años que acuden a endocrinología infantil durante 2018-2019. Tamaño muestral: 23 casos transgénero (16 masculinos y 7 femeninos) y 30 controles cis. Variables del estudio en T0 (pretratamiento) y T1 (tras un año de THC): datos sociodemográficos, Test de Utrecht, Test SDQ-Cas, APGAR familiar, Escala STAI, Test de evaluación de depresión BDI-II. Resultados: Se encuentra mejoría significativa (p

Objectives: To evaluate the psychosocial status of the patients who attend a paediatric endocrinology clinic due to gender incongruity (GI), and to establish the impact on this after one-year of cross hormonal therapy (CHT). Material and methods: An analytical and prospective study conducted on adolescents between 14 and 18 years old with GI, and who attended the Endocrinology Clinic during 2018–2019. The sample included 23 transgender cases (16 male and 7 female cases) and 30 cisgender controls. Study variables were collected at T0 (pre-treatment) and T1 (after one year of CHT) and included sociodemographic data, Utrecht test, SDQ-Cas test, family APGAR test, STAI scale-anxiety Grade, and BDI-II depression assessment test. Results: A significant improvement (P

Resumo Fundamento O conhecimento sobre a própria doença pode ser importante para o autocuidado em pacientes com vários problemas e abrange a informação sobre o diagnóstico até as implicações clínicas mais importantes. Objetivo Identificar o nível de conhecimento de crianças e adolescentes com cardiopatia congênita (CC) sobre a sua doença, e analisar a relação entre o nível de conhecimento e a prática de atividade física. Métodos Estudo transversal com 335 pacientes com CC, de 8 a 13 anos, acompanhados em um serviço de cardiologia pediátrica de referência no Sul do Brasil. Os pacientes foram entrevistados em relação ao seu conhecimento sobre a CC e foi realizada revisão dos prontuários para obtenção de detalhes sobre a cardiopatia e os procedimentos. Foi utilizado o nível de significância p < 0,05. Resultados Mais de 50% das crianças e adolescentes não sabiam referir o nome de sua doença ou explicá-la. Após OR ajustado (ORaj), mostraram potencial para respostas incorretas ou não saber sua doença os pacientes cianóticos em relação aos acianóticos (ORaj: 2,29; IC95%: 1,76-6,71; p=0,019); crianças com menor nível de escolaridade (ORaj: 2,20; IC95%: 1,81-5,86; p=0,025); e não praticantes de atividade física (ORaj: 1,88; IC95%: 1,09-3,45; p=0,011). Conclusão As crianças e adolescentes cianóticos, com menor nível de escolaridade e que não praticavam de atividade física apresentaram pouco conhecimento sobre a sua doença. Há necessidade do desenvolvimento de estratégias de intervenções educativas para aumento do conhecimento e mudança comportamental na promoção da atividade física, de acordo com a complexidade da CC. (Arq Bras Cardiol. 2020; 114(5):786-792)

Developing critical thinking skills appears to be a challenge for higher education institutions. However, little is known about the students’ points of view regarding the methodologies they consider to foster the development of this competence. To answer this question, a total of 263 Spanish university students participated in this study and were asked what they understood by critical thinking and the methodologies they considered to be the most effective for developing it. The results indicated that, based on students’ points of view, there were six methodologies that mainly contributed to developing critical thinking: Debates, project-based learning, practices in real contexts, doing research, cooperative learning, and case studies. These results were unanimous regardless of the student’s understanding of critical thinking: Analyzing/organizing, reasoning/arguing, questioning/asking oneself, evaluating, taking a position/taking a decision, compromising/acting. These findings have important theoretical and practical implications for teachers and educational institutions in relation to the development of critical thinking in higher education.

Dimethyl fumarate (DMF) is a therapy for multiple sclerosis (MS) with undetermined mechanism of action. Here the authors find that clinical response to DMF associates with decrease in IL-17-producing CD8+ T cells (Tc17), delineate molecular pathways involved, and show that DMF suppresses Tc17 pathogenicity in a mouse model of MS.

The first record of the amphioxus Branchiostoma californiense on seagrass patches of Halodule wrightii in the Gulf of California is reported. Sixty individuals (19 males, 18 females, and 23 undifferentiated) were collected in May 2017 at Bahía Balandra, Gulf of California, from subtidal seagrass patches at a depth of 0.5 m at low tide. The length and weight ranged from 15.88–28.44 mm and from 0.01–0.11 g for females and 11.7–27.9 mm and 0.01–0.09 g for males, respectively. The minimum size of sexually mature individuals was 11.70 mm for males and 15.88 mm for females; 62% of the specimens were sexually mature. Analysis of the total length-weight relationship suggested an allometric growth pattern among females, males and undifferentiated individuals, whereas an analysis of the entire sample suggested an isometric growth pattern. Typical and additional morphological characters were used to identify the amphioxi. High morphological variability between individuals was found, suggesting the presence of several morphotypes. Branchiostoma californiense had been previously reported as exclusively associated with bare sandy areas, but our study shows that this species can also be found in seagrass patches, using them as breeding and feeding grounds. Thus, seagrass patches are evidenced as suitable habitats for amphioxus.

Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are still unclear. Here the authors show that a SCFA, pentanoate, suppresses autoimmune inflammation in mouse models of colitis and multiple sclerosis via epigenetic modulation of immune cell metabolic and functional pathways.

Abstract Background This study aimed to evaluate the effect of the intake of yerba mate (YM) and green tea (GT) on serum levels of leptin and paraoxonase-1 (PON-1), compared to control. Methods Controlled, randomized clinical trial (RCT) that evaluated 142 men and women affected by overweight or obesity aged 35–60 years, untreated dyslipidemia and no history of coronary artery disease. Participants were randomized to ingest 1000 mL GT, YM or apple tea (AT, control group) daily, during eight weeks. Serum PON-1 and leptin levels were analyzed by ELISA immunoassay at the beginning (baseline) and after eight weeks of intervention. Results The intake of 1 l of YM/day resulted in significant increase in serum levels of PON-1 (9.7%; p = 0.005). The consumption of GT induced no significant difference in the levels of PON-1 (p = 0.154) and leptin (p = 0.783). Intergroup analysis showed a significant difference (p = 0.036) in the variation of PON-1 levels in the YM group when compared to GT and AT groups. In addition, the increase in PON-1 levels in the YM group was significantly associated with increased HDL-c (p = 0.004). Conclusions The intake of yerba mate increased the antioxidant capacity by increasing serum levels of PON-1 and was positively associated with increased HDL-c, stressing the protective role of this beverage against atherosclerotic diseases. GT intake had no significant effect on serum levels of PON-1 and leptin. Trial registration This study is registered with ClinicalTrials.gov under protocol number NCT00933647.

A partir das ações e negociações presentes na instalação de uma cena de música amplificada, busco apreender o que se entende por “músicas do mundo” ou “world music” em festivais da Europa. Abordo a globalização como um fenômeno situado a partir da etnografia da circulação do grupo Siba e a Fuloresta por dois festivais europeus. Discuto o palco como lugar de legitimação de práticas culturais diversas como “música” e as representações construídas nas relações entre programadores, artistas e público em torno da ideia de “diversidade”, investigando especialmente a fabricação de imaginários de Brasil nesse circuito.

Background OX40 (CD134) is a costimulatory molecule of the tumor necrosis factor receptor superfamily that is currently being investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic αOX40 antibodies in the treatment of patients with cancer has fallen short of the high expectation in earlier-stage trials.Methods Using lymphocytes from resected tumor, tumor-free (TF) tissue and peripheral blood mononuclear cells (PBMC) of 96 patients with hepatocellular and colorectal cancers, we determined OX40 expression and the in vitro T-cell agonistic activity of OX40-targeting compounds. RNA-Seq was used to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs).Results Here, we show that OX40 was overexpressed on tumor-infiltrating CD4+ T cells compared with blood and TF tissue-derived T cells. In contrast to a clinical candidate αOX40 antibody, treatment with an Fc-engineered αOX40 antibody (αOX40_v12) with selectively enhanced FcγRIIB affinity, stimulated in vitro CD4+ and CD8+ TIL expansion, as well as cytokine and chemokine secretions. The activity of αOX40_v12 was dependent on FcγRIIB engagement and intrinsic CD3/CD28 signals. The transcriptional landscape of CD4+ and CD8+ TILs shifted toward a prosurvival, inflammatory and chemotactic profile on treatment with αOX40_v12.Conclusions OX40 is overexpressed on CD4+ TILs and thus represents a promising target for immunotherapy. Targeting OX40 with currently used agonistic antibodies may be inefficient due to lack of OX40 multimerization. Thus, Fc engineering is a powerful tool in enhancing the agonistic activity of αOX40 antibody and may shape the future design of antibody-mediated αOX40 immunotherapy.

Abstract Background: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. Objective: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. Methods: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO and LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. Results: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. Conclusion: Statin treatment is efficient in lowering lipids in children with FH. There is need of large, long-term and randomized controlled trials to establish the long-term safety of statins.

Objective: Brazil is a large, heterogeneous, and diverse country, marked by social, economic, and regional inequalities. Stillbirth is a global concern, especially in low‐ and middle‐income countries. This study investigated the prevalence and possible determinants of stillbirth in different regions of Brazil. Methods: This is a cross‐sectional study including all women of reproductive age who had had a pregnancy in the last five years, enrolled in the most recent Brazilian Demographic and Health Survey (DHS/PNDS‐2006/07). Logistic regression was used to assess the association between region and other maternal characteristics and stillbirth risk. Results: The prevalence of stillbirth in Brazil was 14.82 per 1000 births, with great variation by region of the country, and a higher prevalence among the most deprived. The North and Northeast regions had the highest odds of stillbirth compared to the Center‐West, which persisted after adjustment for multiple confounders – including deprivation level and ethnicity. Low maternal age and maternal obesity were also related to higher odds of stillbirth. Conclusion: In Brazil, the region influences stillbirth risk, with much higher risk in the North and Northeast. Variation in socioeconomic level does not explain this finding. Further research on the subject should explore other possible explanations, such as antenatal care and type of delivery, as well as the role of the private and public health systems in determining stillbirth. Preventive strategies should be directed to these historically disadvantaged regions, such as guaranteeing access and quality of care during pregnancy and around the time of birth.

IFN-γ signalling inhibits production of IL-9, the defining cytokine of the Th9 cell subset. Here the authors show that IFN-γ does this by driving IRF1 to compete with IRF4 forIl9promoter binding and skewing these cells towards a Th1 phenotype, an effect that reduces asthmatic inflammation in mice.

This article discusses the heritagisation of folia de reis, a religious and musical practice in Minas Gerais (Brazil). It focuses on the articulations and gaps between the folias de reis groups and the ICH policies in terms of their respective conceptions and uses of the music. An ethnography on the Folia de Reis do Campo Belo reveals the connections between music, religion and memory through which the foliões conceive their heritage. Yet it is the “music-object” paradigm that prevails in the public policies, in line with the parameters of conventional cultural production: the performance formats are glorified, and one of the instruments, the viola, declared “intangible cultural heritage”, has a metonymic relationship with the practice of folia. The aim, therefore, is to examine the intersection of the tangible and intangible in the heritagisation process. Our conclusion points out the participatory dimension of the intangible heritage protection policies, and the challenge of promoting the appreciation of heritage in everyday life through education and collaborative research.

Objective: The purpose of this study was to assess the effect of a gratitude intervention on a community sample of adults in relation to aspects involving well-being and mental health.Methods: A randomized clinical trial was conducted with 1,337 participants, composed of an intervention group (Gratitude group, n = 446), and two control groups (Hassles group, n = 444 and Neutral Events group, n = 447). Participants assigned to the intervention condition were asked to write daily gratitude lists for 14 days, listing moments they had been grateful for during the day. The outcomes analyzed were affect, depression, happiness and life satisfaction. Participants completed the positive affect and negative affect schedule (PANAS), center for epidemiological studies depression scale (CES-D), subjective happiness scale (SHS), and satisfaction with life scale (SWLS) three times: pre- and post-intervention and at 14 days after the end of the intervention. Due to attrition, the number of participants analyzed was 410.Results: Before the intervention, the groups did not differ in any of the variables examined, and loss to follow-up was random among the three groups. The gratitude intervention managed to increase positive affect, subjective happiness and life satisfaction, and reduce negative affect and depression symptoms. This change was greater than the changes in the control groups in relation to positive affect. In the other outcomes analyzed, similar changes were observed in the gratitude intervention and the neutral events intervention.Conclusion: Some similarities were found between the Gratitude and the Neutral Events groups probably because participants in the last group usually recorded positive events from their days on the lists, turning it into an activity very similar to that proposed to the gratitude group. Some limitations of the study are discussed, such as the high dropout rate for self-performed online interventions. It is necessary to investigate which characteristics of an intervention ensure better results when the intervention is performed online.Trial Registration: The study is registered in the Brazilian Clinical Trials Registry, under No. RBR-9j9myd. Trial URL: http://www.ensaiosclinicos.gov.br/rg/RBR-9j9myd/.

ABSTRACT Objective: To evaluate the physical activity level and functional capacity of children and adolescents with congenital heart disease and to describe correlations between functionality, surgical and echocardiographic findings, metabolic and inflammatory profile and differences between acyanotic and cyanotic heart defects. Methods: A cross-sectional study including children and adolescents with congenital heart disease between six and 18 years old that were evaluated with the 6-minute walk test (6MWT) to assess functional capacity. The short version form of the International Physical Activity Questionnaire (IPAQ) was performed to evaluate physical activity levels. Also, echocardiography and blood collection, to evaluate the metabolic (blood glucose, lipids, insulin) and inflammatory markers (C-reactive protein), were assessed. Results: Twenty-five individuals were evaluated. Of them, 14 had acyanotic heart defects and 11 cyanotic heart defects. Mean age was 12.0±3.7 years, and 20 (80%) were male. IPAQ showed that six (24%) individuals were very active, eight (32%) were active, nine (36%) had irregular physical activity, and two (8%) were sedentary. The mean distance walked in the 6MWT, considering all studied individuals, was 464.7±100.4 m, which was 181.4±42.0 m less than the predicted (p=0.005). There was a positive correlation between Z score 6MWT and the number of surgical procedures (r=-0.455; p=0.022). Conclusions: Children and adolescents with congenital heart disease have low functional capacity, but they are not completely sedentary.

O objetivo do estudo foi verificar o risco para síndrome coronariana aguda, em pacientes adultos jovens internados em um hospital de cardiologia do Rio Grande do Sul, entre setembro de 2010 e junho de 2012. Estudo transversal, com pacientes de 20 a 50 anos, ambos os sexos, com diagnóstico de síndrome coronariana aguda. Analisados fatores de risco cardiovasculares como: idade, história familiar positiva, tabagismo, índice de massa corpórea, atividade física, pressão arterial, glicemia, triglicerídeos, colesterol total e lipoproteína de alta densidade. Os resultados evidenciaram que dos 96 pacientes, 52(54,2%) eram do sexo masculino, idade média de 43±7,4 anos e 57(59,4%) com infarto agudo do miocárdio com supradesnivelamento do segmento ST. Os fatores de risco mais prevalentes foram: história familiar positiva 53(55,2%) e tabagismo 49(51%). A abordagem multidisciplinar deve ser instituída para modificação do estilo de vida, evitando ocorrência de novos eventos. ABSTRACT This cross-sectional study to determine risk for acute coronary syndrome in young adults examined patients of both sexes aged 20-50 years admitted to a cardiology hospital in Rio Grande do Sul State between September 2010 and June 2012 with diagnoses of acute coronary syndrome. The cardiovascular risk factors analyzed were: age, family history, smoking, body mass index, physical activity, blood pressure, glucose, triglycerides, total cholesterol and high density lipoproteins. The results comprised 96 patients, mean age 43±7.4 years, 52(54.2%) of them male, and 57(59.4%) with acute myocardial infarction with ST-segment elevation. The most prevalent risk factors were positive family history 53(55.2%) and smoking 49(51%). A multidisciplinary approach should be introduced to modify lifestyle and prevent new events. RESUMEN El objetivo del estudio fue determinar el riesgo de síndrome coronario agudo, en pacientes adultos jóvenes internados en un hospital de cardiología de Rio Grande do Sul, entre septiembre de 2010 y junio de 2012. Estudio transversal realizado junto a pacientes de 20 a 50 años, de ambos sexos, con diagnóstico de síndrome coronario agudo. Se analizaron los factores de riesgo cardiovascular como: edad, historia familiar, tabaquismo, índice de masa corporal, actividad física, presión arterial, glucemia, triglicéridos, colesterol total y lipoproteína de alta densidad. Los resultados consistieron en 96 pacientes, 52(54,2%) hombres, promedio de edad 43±7,4 años y 57(59,4%) con infarto agudo de miocardio y supradesnivelación del segmento ST. Los factores de riesgo más frecuentes fueron: historia familiar 53(55,2%) y tabaquismo 49(51%). El enfoque multidisciplinario debe ser instituido para la modificación de estilo de vida evitando la aparición de nuevos eventos. DOI: http://dx.doi.org/10.12957/reuerj.2015.5934

Abstract Background: Long-term safety, effectiveness and criteria for treatment with statins in children are still unclear in clinical practice. There is very limited evidence for the use of medication to treat children with dyslipidemia secondary to obesity who do not respond well to lifestyle modification. Objective: Systematic review of randomized clinical trials of statin use to treat children and adolescents with dyslipidemia secondary to obesity. Methods: We performed a search in PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO, and LILACS for data to evaluate the effect of statins on: improvement of surrogate markers of coronary artery disease in clinical outcomes of adulthood; increased serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipropotein B (APOB); and decreased serum levels of high-density lipoprotein cholesterol (HDL-C) from inception to February 2016. Participants were children and adolescents. Results: Of the 16793 potentially relevant citations recovered from the electronic databases, no randomized clinical trials fulfilled the inclusion criteria for children with dyslipidemia secondary to obesity. Conclusions: We found no specific evidence to consider statins in the treatment of hypercholesterolemia secondary to obesity in children. The usual practice of extrapolating findings from studies in genetic dyslipidemia ignores the differences in long-term cardiovascular risks and the long-term drug treatment risks, when compared to recommendation of lifestyle changes. Randomized clinical trials are needed to understand drug treatment in dyslipidemia secondary to obesity.