456 research outputs found

    Relations of girls students to martial arts knowledge in Physical Education lessons

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    Based on “relation to knowledge” theory of Bernard Charlot, the question of this investigation is: what are the relations of meaning and mobilization of girls with martial arts knowledge? This a qualitative study with the following procedures: lessons observation of judo content in a seventh grade class of Midle School; and semi-estructured interviews with 17 class students. The results indicated less mobilization of girls in comparison to boys. The elements unfavorable to female mobilziation were separated into three categories: (i) masculinization and machismo in martial arts; (ii) the fear of being hurt; (iii) embarrassment to expose yourself. To conclude, is important to emphasize that difficulties of gender and martial arts does not mean discarding them from the pedagogical process, but rather encourages the creation of experiences that subvert and trangress such barries

    Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II : a phase 2 trial in Brazil

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    In Hunter syndrome (mucopolysaccharidosis II [MPS-II]),systemic accumulation of glycosaminoglycans (GAGs) dueto a deficiency of iduronate-2-sulfatase (IDS), caused by mu-tations in theIDSgene, leads to multiple somatic manifesta-tions and in patients with the severe (neuronopathic)phenotype, also to central nervous system (CNS) involve-ment. These symptoms cannot be effectively treated withcurrent enzyme-replacement therapies, as they are unableto cross the blood-brain barrier (BBB). Pabinafusp alfa, anovel IDS fused with an anti-human transferrin receptorantibody, was shown to penetrate the BBB and to addressneurodegeneration in preclinical studies. Subsequent phase1/2 and 2/3 clinical studies in Japan have shown markedreduction of GAG accumulation in the cerebrospinalfluid(CSF), along with favorable clinical responses. A 26-week,open-label, randomized, parallel-group phase 2 study wasconducted in Brazil to further evaluate the safety and efficacyof intravenously administered pabinafusp alfa at 1.0, 2.0,and 4.0 mg/kg/week in MPS-II patients. The safety profilesin the three dosage groups were similar. Neurodevelopmentalevaluation suggested positive neurocognitive signals despite arelatively short study period. The 2.0-mg/kg group, whichdemonstrated marked reductions in substrate concentrationsin the CSF, serum, and urine, was considered to provide thebest combination regarding safety and efficacy signals

    Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology

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    Background:Heme and iron homeostasis is perturbed in Alzheimer’s disease (AD); therefore, the aim of the studywas to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN),mild cognitive impairment (MCI), and AD individuals from the Australian Imaging, Biomarker and Lifestyle FlagshipStudy of Ageing (AIBL) and Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohorts.Methods:Non-targeted proteomic analysis by high-resolution mass spectrometry was performed to quantify relativeprotein abundances in plasma samples from 144 CN individuals from the AIBL and 94 CN from KARVIAH cohorts and21 MCI and 25 AD from AIBL cohort. ANCOVA models were utilized to assess the differences in plasma proteinsimplicated in heme/iron metabolism, while multiple regression modeling (and partial correlation) was performed toexamine the association between heme and iron proteins, structural neuroimaging, and cognitive measures.Results:Of the plasma proteins implicated in iron and heme metabolism, hemoglobin subunitβ(p= 0.001) was significantlyincreased in AD compared to CN individuals. Multiple regression modeling adjusted for age, sex, APOEε4 genotype, anddisease status in the AIBL cohort revealed lower levels of transferrin but higher levels of hemopexin associated with augmentedbrain amyloid deposition. Meanwhile, transferrin was positively associated with hippocampal volume and MMSE performance,and hemopexin was negatively associated with CDR scores. Partial correlation analysis revealed lack of significant associationsbetween heme/iron proteins in the CN individuals progressing to cognitive impairment.Conclusions:In conclusion, heme and iron dyshomeostasis appears to be a feature of AD. The causal relationship betweenheme/iron metabolism and AD warrants further investigation

    Preference, importance and participation of girls and boys in the Physical Education High School class

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    O objetivo do estudo é compreender, sob perspectiva discente, a interferência do marcador gênero nas relações dos/as estudantes de Ensino Médio com a Educação Física (EF). Trata-se de uma pesquisa descritiva com 94 alunos e 88 alunas de 8 escolas estaduais de São Paulo (Brasil), que levantou informações de gosto, importância e participação na disciplina EF, a partir de aplicação de questionário estruturado. Os resultados indicam que meninos atribuem maior importância, gostam e participam mais do que as meninas. Contudo, não é possível afirmar que meninas desgostam, não participam e não atribuem importância. Em cotejo com a literatura, a participação das alunas na EF, além do fator gosto, está concatenada a obrigação ou via “obediência-subversiva” no ambiente ambíguo escolar, de discursos explícitos de igualdade de condições e de práticas implícitas segregacionistas de gênero; por sua vez, a referida ambiência implícita favorece a “colonização” de meninos nas aulas de EF. Concluímos que são os docentes (homens e mulheres) que podem problematizar a desigualdade e ajudar a instituir uma EF com equidade de gênero.The aim of this study is to understand, from the student’s perspective, the interference of gender marker in High School students in relation to Physical Education (PE). This is a descriptive study with 94 boys and 88 girls from 8 public schools of São Paulo State (Brazil), which raised information on preference, importance and participation in PE classes, through the application of a structured questionnaire. The results indicate that boys give greater importance to like and participate more in the class than girls. However, it is not possible to say that girls dislike it, do not participate and do not give importance to it. Research in the literature shows that the participation of students in PE, beyond preference, is associated with the obligation or via “subversive obedience” in the ambiguous school environment, with explicit speeches of equal conditions and implicit gender segregationist practices. On the other hand, the implicit environment supports the “colonization” of boys in PE classes. We conclude that teachers (men and women) are the ones who can problematize inequality and assist students to establish gender equity PE.Facultad de Humanidades y Ciencias de la Educació

    Enzyme replacement therapy with pabinafusp alfa for neuronopathic mucopolysaccharidosis II : an integrated analysis of preclinical and clinical data

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    Enzyme replacement therapy (ERT) improves somatic manifestations in mucopolysaccharidoses (MPS). However, because intravenously administered enzymes cannot cross the blood–brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT in order to achieve CNS effects, but the burdens on patients are inimical to long-term administrations. However, since pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in a mouse model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT that is effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the previously obtained preclinical and clinical evidence related to the use of this drug, presents latest data, and discusses the preclinical, translational, and clinical challenges of evaluating, ameliorating, and preventing neurodegeneration in patients with MPS-II

    Emancipation under the great recession in Spain.

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    ABSTRACT: In this paper we document the behavior of emancipation over one of the biggest boom–bust cycles experienced by the Spanish economy. In principle, the economic difficulties faced by the Spanish youth during the last recession would have hampered a normal emancipation pace. However, we find that the proportion living away from parents among those aged 18–40 has not decreased but increased from 44 % during the boom (2005–2008) to 46 % during the bust (2009–2013). A simple decomposition reveals that this is mainly driven by the substantial rise in the emancipation rate among the full-time employed workers during the bust. To explain this change we discuss several factors such as macroeconomic conditions, rental subsidy policy, higher labor mobility, selection bias, reverse causation, timelag in adjustment and secular trend.MEC(IP: María Paz Espinosa Alejos, UPV

    Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development

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    © The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.This work was financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. This research was also funded by: PTDC/MED-ONC/28660/2017 from Fundação para a Ciência e Tecnologia (FCT) to A.R.G. A.R.G is recipient of Researcher Grant CEECIND/02699/2017 from FCT. The biobanking of CRC samples from Hospital Santa Maria, Lisbon, Portugal was supported by FCT research grant PIC/IC/82821/2007. This work was produced with the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016.info:eu-repo/semantics/publishedVersio

    Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

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    BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. CASES PRESENTATION: We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. CONCLUSION: The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB

    HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome

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    © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.The biobanking of CRC from Hospital Santa Maria, Lisbon, Portugal, was supported by a grant from the Official Portuguese Funding Agency for Science and Technology (FCT: PIC/IC/82821/2007).info:eu-repo/semantics/publishedVersio
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