Dietary supplementation with chestnut (Castanea sativa) reduces abdominal adiposity in FVB/n mice: a preliminary study

The production of chestnut (Castanea sativa Miller) is mostly concentrated in Europe. Chestnut is recognized by its high content of antioxidants and phytosterols. This work aimed to evaluate the e ects of dietary chestnut consumption over physiological variables of FVB/n mice. Eighteen FVB/n male 7-month-old mice were randomly divided into three experimental groups (n = 6): 1 (control group) fed a standard diet; 2 fed a diet supplemented with 0.55% (w/w) chestnut; and 3 supplemented with 1.1% (w/w) chestnut. Body weight, water, and food intake were recorded weekly. Following 35 days of supplementation, the mice were sacrificed for the collection of biological samples. Chestnut supplementation at 1.1% reduced abdominal adipose tissue. Lower serum cholesterol was also observed in animals supplemented with chestnut. There were no significant di erences concerning the incidence of histological lesions nor in biochemical markers of hepatic damage and oxidative stress. These results suggest that chestnut supplementation may contribute to regulate adipose tissue deposition.This work is supported by National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020, CIMO (UIDB/00690/2020) and UIDB/CVT/00772/2020 Interreg Program for the financial support of the Project IBERPHENOL, Project Number 0377_IBERPHENOL_6_E; co-financed by European Regional Development Fund (ERDF) through POCTEP 2014-2020. This work was also supported by VALORIZEBYPRODUCTS Project, reference n.º 029152, funded by Portuguese Foundation for Science and Technology (FCT) and co-financed by the European Regional Development Fund (FEDER) through COMPETE 2020 - Operational Competitiveness and Internationalization Programme (POCI). This work was also financially supported by Project UID/EQU/00511/2019 - Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE funded by national funds through FCT/MCTES (PIDDAC) and Project “LEPABE-2-ECO-INNOVATION” – NORTE-01-0145-FEDER-000005, funded by Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), by the Research Centre of the Portuguese Institute of Oncology of Porto (CI-IPOP 37-2016) and by the Interact R&D project, operation number NORTE-01-0145-FEDER-000017, in its ISAC research line, co-financed by the ERDF through NORTE 2020. This work was also supported by PhD fellowship SFRH/BD/136747/2018.info:eu-repo/semantics/publishedVersio

The cyclooxigenase-2 inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observations

Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant e cacy, but also considerable toxicity. This study addresses the chemopreventive e ect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16+/-, n = 10, parecoxib-treated); II (HPV16+/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/- n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn’t modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive e ects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.This work is supported by National Funds by FCT—Portuguese Foundation for Science and Technology, under the projects UID/AGR/04033/2019, UID/CVT/00772/2019 and UID/EQU/00511/2019 - Laboratory for Process Engineering, Environment, Biotechnology and Energy—LEPABE funded by national funds through FCT/MCTES (PIDDAC); Project “LEPABE-2-ECO-INNOVATION”—NORTE-01-0145-FEDER-000005, funded by Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund.info:eu-repo/semantics/publishedVersio

Cardiovascular abnormalities in patients with oral cleft: a clinical-electrocardiographic-echocardiographic study

OBJECTIVES: The present study aims to describe the clinical, electrocardiographic, and echocardiographic cardiological findings in a group of patients with oral clefts. METHODS: This is a prospective cross-sectional study on 70 children (age range from 13 days to 19 years) with oral clefts who attended the multidisciplinary program of a university hospital from March 2013 to September 2014. The patients were evaluated by a pediatric cardiologist and underwent detailed anamnesis, physical examination, electrocardiogram, and echocardiogram. RESULTS: Sixty percent of the patients were male; 55.7% presented with cleft lip and palate, and 40.0% presented with health complaints. Comorbidities were found in 44.3%. Relevant pregnancy, neonatal, family and personal antecedents were present in 55.7%, 27.1%, 67.2%, and 24.3% of the patients, respectively. Regarding the antecedents, 15.2% of the patients presented with a cardiac murmur, 49.0% with a familial risk of developing plurimetabolic syndrome, and 6% with family antecedents of rheumatic fever. Electrocardiographic evaluation showed one case of atrioventricular block. Echocardiograms were abnormal in 35.7% of the exams, including 5 cases of mitral valve prolapse — one of which was diagnosed with rheumatic heart disease. CONCLUSION: The finding of a family risk of developing plurimetabolic syndrome and a diagnosis of rheumatic heart disease indicates that patients with oral clefts may be more prone to developing acquired heart disease. Thus, our findings highlight the importance of anamnesis and methodological triangulation (clinical-electrocardiographic-echocardiographic) in the investigation of patients with oral clefts and emphasize that cardiological follow-up to evaluate acquired and/or rhythm heart diseases is necessary. This strategy permits comorbidity prevention and individualized planned treatment

Učinci ekstrakta Cytinus hypocistis (L.) L. u životinjskom modelu neoplazije inducirane papiloma virusom

Infections with certain types of papillomavirus, such as the human papillomavirus 16 (HPV16), are associated with the development of preneoplastic lesions and cancers of the anogenital, and head and neck regions. Cytinus hypocistis (L.) L. extracts are composed of substances presenting antiproliferative, antioxidant, anti-inflammatory and antibacterial properties, which might be promising as new therapeutic compounds. This study analysed the influence of topical application of an extract obtained from C. hypocistis (CH) on K14-HPV16 and FVB/n mice to evaluate its therapeutic and toxicological properties. To achieve the study goals, 30 female mice, 33–37 weeks old, were divided into six groups (n=5/group): I (HPV+CH3.1); II (HPV+CH6.2); III (HPV+CH12.4); IV (FVB/n+CH12.4); V (HPV+control) and VI (FVB/n+-control). CH was applied topically to both ears for 28 days. After this period, all animals were sacrificed for samples collection. Skin lesions were classified histologically. Toxicological parameters included haematological and biochemical blood markers, and hepatic oxidative stress analysis. Transgenic animals showed a decrease in mean body weight regardless of the concentration of extract applied. The extract had no influence on physiological parameters, organ weight, or biochemical and oxidative stress parameters. Histology demonstrated the presence of proliferative epithelial lesions in the skin and oral mucosa of K14-HPV16 mice, with no association with the application of this extract. Overall, the application of CH extract had no influence on the skin lesions and was well tolerated by the animals in these concentrations.Infekcije određenim vrstama papiloma virusa, poput humanog papiloma virusa 16 (HPV16), povezane su s razvojem preneoplastičnih lezija i karcinoma anogenitalnog područja i područja glave i vrata. Ekstrakti Cytinus hypocistis (CH) sadrže tvari koje pokazuju antiproliferativna, antioksidativna, protuupalna i antibakterijska svojstva te bi stoga mogle predstavljati nove, obećavajuće terapijske spojeve. Cilj je ovog rada bio analizirati utjecaj topikalne primjene ekstrakta dobivenog iz C. hypocistis (L.) L. na K14-HPV16 i FVB/n miševima za procjenu njegovih terapijskih i toksikoloških svojstava. Za postizanje ciljeva istraživanja, trideset ženki miševa starosti 33-37 tjedana podijeljeno je u šest skupina (n=5/ skupini): I (HPV+CH3,1); II (HPV+CH6,2); III (HPV+CH12,4); IV (FVB/n+CH12,4); V (HPV+kontrola) i VI (FVB/n+kontrola). CH je tijekom 28 dana topikalno primijenjen na oba uha. Nakon tog razdoblja sve životinje su žrtvovane u svrhu prikupljanja rezulata. Lezije kože su histološki klasificirane. Toksikološki parametri uključivali su hematološke i biokemijske markere krvi te analizu oksidativnog stresa jetre. Transgenične životinje pokazale su smanjenje srednje tjelesne mase, bez obzira na primijenjenu koncentraciju ekstrakta. Ekstrakt nije utjecao na fiziološke parametre, masu organa ili parametre biokemijskog i oksidativnog stresa. Histološki je dokazana prisutnost proliferativnih epitelnih lezija na koži i oralnoj sluznici K14-HPV16 miševa, bez povezanosti s primjenom ovog ekstrakta. Općenito, primjena CH ekstrakta nije utjecala na lezije kože te su ga životinje dobro podnosile u primijenjenim koncentracijama

Toxicological and anti-tumor effects of a linden extract (Tilia platyphyllos Scop.) in a HPV16-transgenic mouse model

Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. have shown in vitro antioxidant, anti-inflammatory and antitumor properties. The aim of this work was to evaluate the therapeutic properties of a hydroethanolic extract obtained from T. platyphyllos in HPV16-transgenic mice. The animals were divided into eight groups according to their sex and phenotype. Four groups of female: HPV+ exposed to linden (HPV linden; n = 6), HPV+ (HPV water; n = 4), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 4) and four groups of male: HPV+ exposed to linden (HPV linden; n = 5), HPV+ (HPV water; n = 5), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 7). The linden (Tilia platyphyllos Scop.) extract was orally administered at a dose of 4.5 mg/10 mL per animal (dissolved in water) and changed daily for 33 days. The hydroethanolic extract of T. platyphyllos consisted of protocatechuic acid and (-)-epicatechin as the most abundant phenolic acid and flavonoid, respectively, and was found to be stable during the studied period. In two male groups a significant positive weight gain was observed but without association with the linden extract. Histological, biochemical, and oxidative stress analyses for the evaluation of kidney and liver damage support the hypothesis that the linden extract is safe and well-tolerated under the present experimental conditions. Skin histopathology does not demonstrate the chemopreventive effect of the linden extract against HPV16-induced lesions. The linden extract has revealed a favourable toxicological profile; however, additional studies are required to determine the chemopreventive potential of the linden extract. This journal isThis work was supported by the project IBERPHENOL, project number 0377_IBERPHENOL_6_E; Interact R&D project, operation number NORTE-01-0145-FEDER-000017, National Funds by FCT – Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020 (CITAB), and project UIDB/ CVT/00772/2020 (CECAV) and the post-graduation grant SFRH/ BD/136747/2018 and 2020.04789.BD; the authors are also grateful to FCT, Portugal and FEDER under programme PT2020 for financial support to CIMO (UIDB/00690/2020) and L. Barros acknowledges the national funding by FCT, P. I., through the institutional scientific employment program-contract. The authors would like to thank Cantinho das Aromáticas organic farmers from Vila Nova de Gaia (Portugal) for providing the samples. This work was financially supported by: Base Funding - UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE - funded by national funds through the FCT/MCTES (PIDDAC).info:eu-repo/semantics/publishedVersio

Efeito da aplicação repetida de Cytinus hypocistis em murganhos transgénicos (K14HPV16): avaliação de humane endpoints

Em, 1959 Russel e Burch propuseram os 3Rs (Reduce, Refine e Replacement) em experimentação animal e desde então as diversas entidades envolvidas na temática têm feito esforços conjuntos para os aplicar (1). Nesse sentido foi gradualmente introduzida a avaliação e registo dos humane endpoints (HE) dos animais durante procedimentos experimentais, para monitorizar o seu sofrimento e tomar decisões sobre a necessidade, ou não, de finalizar o ensaio antes da data prevista (2). Contudo, apesar das exigências legais, observa-se grande escassez de publicações sobre a avaliação de HE nos procedimentos com animais de laboratório. Assim, é nosso objetivo com este trabalho apresentar os HE durante a aplicação diária de um creme com Cytinus hypocistis numa estirpe de murganhos transgénicos.Financiamento nacional pela FCT, Fundação para a Ciência e a Tecnologia, no âmbito da bolsa de doutoramento 2020.07675.BD de Beatriz Medeiros Fonseca.info:eu-repo/semantics/publishedVersio

Infants and newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB registry: a unique and challenging population

SIMPLE SUMMARY: Malignant rhabdoid tumors (MRT) are deadly tumors that predominantly affect infants and young children. Even when considering the generally young age of these patients, the treatment of infants below the age of six months represents a particular challenge due to the vulnerability of this patient population. The aim of our retrospective study was to assess the available information on prognostic factors, genetics, toxicity of treatment and long-term outcomes of MRT. We confirmed that, in a cohort of homogenously treated infants with MRT, significant predictors of outcome were female sex, localized stage, absence of a GLM and maintenance therapy, and these significantly favorably influence prognosis. Stratification-based biomarker-driven tailored trials may be a key option to improve survival rates. ABSTRACT: Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option

Infants and Newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB Registry: A Unique and Challenging Population

Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option

Práticas artísticas no ensino básico e secundário

Sobre a Matéria-Prima, há novidades e perigos. O tempo vivido na Europa e no contexto global tem vindo a acentuar a urgência das prioridades quantificadas, com um discurso dominante onde há menos política (pessoas) e mais representação económica (coisas). O correlato entre pessoas e coisas é, como sabemos, o dinheiro, ou trabalho reificado. A crise europeia, em torno da dívida soberana e dos maiores orçamentos do mundo, da capacidade da sua gestão na linguagem dura dos mercados e das taxas de juro veio modificar os objetivos imediatos da Europa, que em 2000 eram ambiciosos — “a sociedade mais competitiva do mundo em 2010” — para uma estratégia de emergência, agora chamada horizonte 2020. Este é o panorama ideal para colocar o ensino artístico em risco. Os fóruns internacionais passaram a valorizar os resultados da educação em rankings e sondagens de aproveitamento, cuja principal estratégia e preocupação é a mensurabilidade e comparabilidade, como são exemplo os relatórios PISA: avaliam-se em todos os países, as competências em Ciências, Matemática e Língua Materna. A matéria-prima de amanhã corre riscos de desaparecer gradualmente, pelos cortes de carga horária, pela concepção extracurricular da educação artística, pela sua perceção menorizada em função das concepções competitivas da sociedade contemporânea globalizada.info:eu-repo/semantics/publishedVersio

The state of research into children with cancer across Europe : new policies for a new decade

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.peer-reviewe