Resistencia química del Hormigón. XXVIII. Contribución al estudio del sistema Cemento P-550-ARI hidratado-disolución de sulfato de sodio

In this work, which is the following of the others, the performance of a portland cement of a high initial resistance (P-550-ARI) —with a calculated content (Bogue) of 39,2 - 25,7 - 9,9 - 12,0 and 6,9% of C3S - C2S - C3A - C4AF and CaSO4, respectively— is studied when it is submitted to the action of an sodium sulfate solution [2,1 g/l of Na2S04 1,42 g/l of SO4 (II) 1,48 X 10-2 moles/litre of SO4 (II)] running across the beds of granulated cement, made with this hydrated cement cured during 7 or 28 days, determining: a) The evolution of the content on ions Ca (II) and SO4 (II) on the taken diverse fractions of sodium sulfate solution which have run across those beds, so as this of the pH and of the conductivity, b) the variation in the amount of these ions that are forming the correspondents compounds, in the hydrated cement from the beds that have been submitted before and after to the action of the sodium sulfate solution, and c) the structural modifications undergone by the crystalline compounds of the hydrated cement from the beds submitted to the action of the sodium sulfate solution.En el presente trabajo, continuación de otros, se estudia el comportamiento de un cemento portland de alta resistencia inicial (P-550-ARI) con unos contenidos calculados (Bogue) de C3S, C2S, C3A, C3AF y CaS04 del 39,2 - 25,7 - 9,9 - 12,0 y 6,9%, respectivamente, cuando se somete a la acción de una disolución de sulfato de sodio [2,1 g/l de Na2SO4 1,42 g/l de SO4 (II) 1,48 X 10-2 moles/litro de SO4 (ll)], que atraviesa sendos lechos granulados fabricados con dicho cemento hidratado y curado durante 7 y 28 días, determinando: a) la evolución del contenido de iones Ca (II) y SO4 (II) en las diversas fracciones recogidas de la disolución de sulfato de sodio, que han atravesado los lechos de cemento, así como la del pH y de la conductividad, b) la variación de las cantidades de dichos iones, que se encuentran formando los compuestos correspondientes, en el cemento hidratado de los lechos antes y después de someterlos a la acción de la disolución de sulfato de sodio, c) las modificaciones estructurales experimentadas por los compuestos cristalinos del cemento hidratado de los lechos sometidos a la acción de la disolución mencionada

Level of Physical Activity and Its Relationship to Self-Perceived Physical Fitness in Peruvian Adolescents

Background: Physical activity and physical fitness play an important role in adolescence. Both are considered to be indicators of the current and future health status of young adults. The main objective of this article was to report the normative values of the Physical Activity Questionnaire for Adolescents (PAQ-A) and the International Fitness Scale (IFIS) instruments in Peruvian school adolescents. Methods: A sample of 1229 participants (622 girls and 607 boys) aged between 12 and 17 years was used. The type of study was descriptive-comparative. All measures used were obtained by means of self-administered instruments. The PAQ-A was used to assess the level of physical activity and the IFIS to assess the self-perceived physical fitness level of the adolescents. Results: It was observed that the PAQ-A questionnaire results obtained from the total sample was 2.34; significantly higher for boys (2.41) compared with girls (2.27). For the IFIS, the total score was 3.07, with boys obtaining 3.13 and girls 2.97. Conclusions: It was concluded that there was a direct relationship between the level of PA and self-perceived PF in Peruvian adolescents. Furthermore, adolescent boys were more physically active than girls and they had a better self-perceived PF with the exception of flexibility. Finally, there was a higher weight category involved at the lower level of PA

Insights of Phenolic Pathway in Fruits: Transcriptional and Metabolic Profiling in Apricot (Prunus armeniaca)

There is an increasing interest in polyphenols, plant secondary metabolites, in terms of fruit quality and diet, mainly due to their antioxidant effect. However, the identification of key gene enzymes and their roles in the phenylpropanoid pathway in temperate fruits species remains uncertain. Apricot (Prunus armeniaca) is a Mediterranean fruit with high diversity and fruit quality properties, being an excellent source of polyphenol compounds. For a better understanding of the phenolic pathway in these fruits, we selected a set of accessions with genetic-based differences in phenolic compounds accumulation. HPLC analysis of the main phenolic compounds and transcriptional analysis of the genes involved in key steps of the polyphenol network were carried out. Phenylalanine ammonia-lyase (PAL), dihydroflavonol-4-reductase (DFR) and flavonol synthase (FLS) were the key enzymes selected. Orthologous of the genes involved in transcription of these enzymes were identified in apricot: ParPAL1, ParPAL2, ParDFR, ParFLS1 and ParFLS2. Transcriptional data of the genes involved in those critical points and their relationships with the polyphenol compounds were analyzed. Higher expression of ParDFR and ParPAL2 has been associated with red-blushed accessions. Differences in expression between paralogues could be related to the presence of a BOXCOREDCPAL cis-acting element related to the genes involved in anthocyanin synthesis ParFLS2, ParDFR and ParPAL2

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies

Semantic inference using chemogenomics data for drug discovery

<p>Abstract</p> <p>Background</p> <p>Semantic Web Technology (SWT) makes it possible to integrate and search the large volume of life science datasets in the public domain, as demonstrated by well-known linked data projects such as LODD, Bio2RDF, and Chem2Bio2RDF. Integration of these sets creates large networks of information. We have previously described a tool called WENDI for aggregating information pertaining to new chemical compounds, effectively creating evidence paths relating the compounds to genes, diseases and so on. In this paper we examine the utility of automatically inferring new compound-disease associations (and thus new links in the network) based on semantically marked-up versions of these evidence paths, rule-sets and inference engines.</p> <p>Results</p> <p>Through the implementation of a semantic inference algorithm, rule set, Semantic Web methods (RDF, OWL and SPARQL) and new interfaces, we have created a new tool called Chemogenomic Explorer that uses networks of ontologically annotated RDF statements along with deductive reasoning tools to infer new associations between the query structure and genes and diseases from WENDI results. The tool then permits interactive clustering and filtering of these evidence paths.</p> <p>Conclusions</p> <p>We present a new aggregate approach to inferring links between chemical compounds and diseases using semantic inference. This approach allows multiple evidence paths between compounds and diseases to be identified using a rule-set and semantically annotated data, and for these evidence paths to be clustered to show overall evidence linking the compound to a disease. We believe this is a powerful approach, because it allows compound-disease relationships to be ranked by the amount of evidence supporting them.</p

Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor–positive metastatic breast cancer: Patient-reported outcomes in the PEARL study

Background: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. Patients and methods: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. Results: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs. -2.1 for capecitabine (95% confidence interval [CI], 1.4–8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. Conclusion: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. Trial registration number: NCT02028507 (ClinTrials.gov). EudraCT study number: 2013-003170-27. © 2021 The Author(s

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease

[Background and Aims] To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®.[Methods] Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The ‘switch cohort’ [SC] comprised patients who made the switch from Remicade® to CT-P13, and the ‘non-switch’ cohort [NC] patients remained under Remicade®.[Results] A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2–6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05].[Conclusions] Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.This research has been funded by grants from the Instituto de Salud Carlos III [PI13/00041 and FI17/00143]

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial—PEARL

Background: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. Patients and methods: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. Results: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). Conclusions: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life

Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival.

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival. Conclusions Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.This study was funded by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain, the European Union–European Regional Development Fund (EC07/90772 and PI19/00649), and the Consorcio de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV).S