Objective
To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme ...that would incorporate both antibodies and the cutaneous disease subset as criteria.
Methods
Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death.
Results
The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody–positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20‐year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti–Scl‐70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti‐Scl‐70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti‐Scl‐70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti–RNA polymerase antibody–positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti–U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications.
Conclusion
These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.
One of the main reasons for studying a foreign language is communicating with others, but many students do not feel confidently enough when trying to develop their speaking skills. Among adolescents’ ...frequent activities are that of listening to music while paying attention to song lyrics. We hypothesize that these musical experiences could influence their speaking skills. The present study aims to consider different factors that could influence students’ speaking proficiency. Among these factors, students’ emotional understanding, their willingness to communicate in a FL and their musical experience are considered. One hundred and twenty-four students of English as a foreign language (EFL) in the fourth year of Secondary Education from three different high schools in Spain took part in the study. Oral data were collected through individual interviews and three scales were administered to measure the different factors. Students’ musical experience and emotional response to music were measured through The Absorption in Music Scale, their emotional understanding of verbal texts through The Situational Test of Emotional Understanding – Brief, and their willingness to communicate in the EFL class through Willingness to Communicate Scale. Although no direct connection was found between students’ musical experience and their speaking proficiency, results demonstrate that students with high emotional understanding show better speaking skills and that students with musical experience exhibited higher emotional understanding. We detected a significant positive connection between emotional understanding and all the five parameters considered to assess students’ speaking proficiency. The connection between willingness to communicate in the EFL class and students’ speaking skills is even greater.
We assessed the profile and frequency of malignancy subtypes in a large single-centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc ...patients with different antibody reactivities and explored the temporal association of cancer with the duration between SSc onset and cancer diagnosis.
We conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by review of patient records. We evaluated development of all cancers in this cohort, and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details, including antibody reactivities, were explored to find associations relevant to the risk for development of cancer in SSc patients.
Among 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (6.8%) (P < 0.0001 and P < 0.001, respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 antibodies = 13.6%, P < 0.002, respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP, and SSc patients with anti-RNAP had a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001).
Our study independently confirms, in what is to the best of our knowledge the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate.
Resumen Se presentan los resultados de una investigación cuyo objetivo es contribuir al desarrollo de prácticas pedagógicas innovadoras mediante la instalación de un laboratorio de experimentación ...pedagógica (LAP) en una escuela vulnerable en Chile. Siguiendo los principios de la investigación-acción, se realizaron 15 actividades formativas sobre prácticas innovadoras y se instaló una sala especializada. En paralelo, se hicieron entrevistas, grupos focales y evaluaciones de proceso. Los resultados muestran: (1) el potencial del cambio pedagógico; (2) nuevas formas de habitar el espacio de clases; (3) la valoración de la experimentación pedagógica. Se concluye que la innovación debe ser un proyecto de escuela y debe promover una perspectiva amplia para entender el aprendizaje.
Résumé Ce travail présente les résultats d’une recherche dont l’objectif est de contribuer au développement de pratiques pédagogiques innovantes grace à l’installation d’un laboratoire d’expérimentation pédagogique (LAP) dans une école chilienne vulnérable. Suivant les principes de la recherche-action, 15 activités de formation concernant les pratiques innovantes ont été menées et une salle spécialisée a été mise en place. En parallèle, des entretiens, des groupes de discussion et des évaluations de processus ont été réalisés. Les résultats montrent que: (1) le potentiel de changement pédagogique; (2) de nouvelles façons de vivre et de penser l’espace de la salle de classe; (3) l’évaluation de l’expérimentation pédagogique. La conclusion est que l’innovation doit être un projet d’école et promouvoir une meilleure compréhension de l’apprentissage.
Abstract This paper presents the results of a research project which aimed to contribute to the development of innovative teaching practices by setting up a teaching experimentation laboratory (LAP) in a vulnerable Chilean school. According to the principles of action research, 15 training activities on innovative practices were carried out and a customized room was set up. Meanwhile, interviews, focus groups and process evaluations were carried out. The results show the following: (1) the potential of pedagogical change; (2) new ways of occupying the classroom space; (3) the evaluation of pedagogical experimentation. The conclusion is that innovation should be a school project and should promote a broad perspective for understanding learning.
Resumo Este texto apresenta os resultados de uma pesquisa cujo objetivo é contribuir para desenvolver práticas pedagógicas inovadoras por meio da instalação de um laboratório de experimentação pedagógica (LAP) em uma escola chilena vulnerável. De acordo com os princípios da pesquisa- -ação, foram realizadas 15 atividades formativas sobre práticas inovadoras e instalou-se uma sala especializada. Paralelamente realizaram-se entrevistas, grupos focais e avaliações de processo. Os resultados mostram o seguinte: (1) o potencial da mudança pedagógica; (2) novas formas de habitar o espaço das classes; (3) a avaliação da experimentação pedagógica. Conclui-se que a inovação deve ser um projeto escolar e deve promover uma ampla perspectiva para entender a aprendizagem.
-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of
-acylethanolamines (NAEs), a family of bioactive lipid mediators. ...Previously, we reported
-(cyclopropylmethyl)-6-((
)-3-hydroxypyrrolidin-1-yl)-2-((
)-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (
,
) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior Mock
, 2020, 16, 667-675. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of
. A high-throughput screening hit was modified at three different substituents to optimize its potency and lipophilicity. Conformational restriction of an
-methylphenethylamine group by replacement with an (
)-3-phenylpiperidine increased the inhibitory potency 3-fold. Exchange of a morpholine substituent for an (
)-3-hydroxypyrrolidine reduced the lipophilicity and further increased activity by 10-fold, affording
as a nanomolar potent inhibitor with drug-like properties.
is a suitable pharmacological tool compound to investigate NAPE-PLD function
and
.
La enseñanza de lenguas que tiene en cuenta música y emociones puede ser de gran utilidad. El objetivo principal de este estudio exploratorio ha sido examinar el uso del videoclip en un contexto de ...educación superior con alumnas eslovacas de español como lengua extranjera (ELE). Para tal fin, en primer lugar, se ha mapeado el consumo de videoclips para aprender español. En segundo lugar, se ha planteado un programa intervención en el aula basado en el trabajo con el videoclip a través de las emociones y, por último, se ha medido la respuesta emocional del alumnado. Los resultados revelan que la mayoría de las estudiantes muestra su conformidad para utilizar el vídeo musical en clase de ELE con el programa de intervención diseñado. Consiguientemente, el vídeo musical resulta una herramienta efectiva para trabajar la competencia comunicativa audiovisual y las emociones en clase de lengua extranjera a nivel universitario.
The current European context is characterised by the emergence of socio-political tensions that threaten to derail the cohesion objectives traditionally promoted by the authorities of the European ...Union. With EU citizenship in the shadow of Brexit, the fear of dismemberment of the current Europe of the 28 looms over a renewed debate on concepts like European identity, European citizenship or EU legitimacy and the involvement of its constituents in European affairs, as well as the role of education for promoting democratic awareness among young Europeans. This work aims to collect, appraise and synthesise qualitative evidence obtained in primary research exploring the perceptions of European university students about their civic and cultural identity. This systematic analysis sets out to identify predictors of positive self-identification with the EU and its institutions, focusing on the impact that different educational interventions have had on the attitudes and perceptions expressed by university students, and the importance of foreign language learning in the results obtained. The authors report their assessment of quality of the findings in a Cochrane-style qualitative evidence synthesis (QES), based on the GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) method. The 12 informed findings described in this study support decision-making in future education policy formulation.
Intraperitoneal pressure (IPP) is gaining consideration as a relevant parameter of peritoneal dialysis (PD) in adults, although many of its aspects are still pending clarification. We address here ...its stability over time and the validity of the usual method of clinical measurement, as proposed by Durand in 1992 but never specifically validated. We performed this validation by comparing Durand’s method and direct measurements with a central venous pressure system. We performed a total of 250 measurement pairs in 50 patients with different intraperitoneal volumes plus in-vitro measurements with a simulated peritoneum. Absolute differences between the two systems in vivo were 0.87 ± 0.91 cmH2O (range 0–5 cmH2O); only 6.4% of them were ≥3 cmH2O. In vitro results for both methods were identical. We also compared IPP measurements in the same patient separated by 1–4 h (514 measurement pairs in 136 patients), 1 week (92 pairs in 92 patients), and 2 years (34 pairs in 17 patients). Net differences of measurements separated by hours or 1 week were close to 0 cmH2O, with oscillations of 1.5 cmH2O in hours and 2.3 cmH2O in 1 week. IPP measured 2 years apart presented a net decrease of 2.5 ± 4.9 cmH2O, without correlation with body mass index changes or any other usual parameter of PD. In hours, 7% of IPP differences were >3 cmH2O, 22% in 1 week, and 50% in 2 years. In conclusion, Durand’s method is precise enough to measure IPP in peritoneal dialysis. This parameter is not stable over long timescales, so it is necessary to use recent measurements.
La educación transmedia ha irrumpido en el campo educativo en los últimos años generando nuevas formas de aprendizaje activo centrado en los estudiantes. Sin embargo, aún se desconoce su efectividad ...y cómo afecta al aprendizaje de lenguas extranjeras. En este artículo se revisa de manera sistemática estudios de la aplicación de Transmedia Storytelling o Narrativas Transmedia para detallar los beneficios del resultado de su aplicación y los principales logros alcanzados por los estudiantes en el aprendizaje de lenguas extranjeras. Esta síntesis cualitativa, que surge de la revisión de estudios publicados al respecto desde el año 2010 al 2020, permite describir el estado actual de la cuestión y recomendar esta innovadora técnica metodológica en el contexto educativo para el desarrollo de las competencias lingüísticas de una lengua extranjera.
Abstract
Understanding how older people respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical if we are to confront the coronavirus disease 2019 (COVID-19) pandemic and ...establish effective vaccination strategies. Immunosenescence reduces the ability to respond to neoantigens and may compromise the life of infected individuals. Here, we analyzed the immunological memory to SARS-CoV-2 in 102 recovered patients aged over 60 years several months after the infection had been resolved. Specific memory T lymphocytes against the virus were measured by interferon-γ (IFN-γ) and granzyme B release by ELISpot; memory B-lymphocyte responses were quantified by detection of anti-S IgG1 producer cells by ELISpot and anti-S and anti-N antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than 7 months after the infection in some of them. Fewer patients maintained memory B lymphocytes, but antibodies, mainly anti-S, were highly durable and positively correlated with T responses. More robust humoral responses were found in patients who had more severe symptoms and had been admitted to hospital. We concluded that specific immunity against SARS-CoV-2 is effectively preserved regardless of age, despite the great heterogeneity of their immune responses, and that memory T lymphocytes and anti-S IgG might be more durable than memory B cells and anti-N IgG.
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