Gender differences in adventure tourists who practice kayaking in Extremadura

Adventure tourism is among the sectors that has experienced the greatest growth in participation in recent years. In addition, it provides a unique opportunity to generate different benefits for rural populations as well as for the preservation of their environment. The objective of this study was to analyze gender differences in the profile, estimated expenditure, perception of economic impact and satisfaction of adventure tourists visiting the Valle del Jerte (Extremadura, Spain) for kayaking activities. The sample was composed of 511 tourists who kayaked in the Valle del Jerte. Gender differences were analyzed by the Mann-Whitney U test in continuous variables and Pearson’s chi-square test in categorical variables. The predominant profile of the kayaking tourist is Spanish, married, employed, with university education, lives with their partner with children at home, chooses a rural home for accommodation, travels with companions, uses their own car for transportation, spends 550 euros on average, has good perceptions of the economic impact of the activity on the destination and is satisfied with the kayak service received. This information is relevant for public and private organizations as well as for the local community to be able to offer services more oriented to the tourist who engages in these activities, as well as to attract more tourists

Cyclooctyne [60]fullerene hexakis adducts: a globular scaffold for copper-free click chemistry

The synthesis of a new highly symmetric hexakis adduct of C60 appended with 12 cyclooctyne moieties has been carried out. This compound has been used for the copper-free strain-promoted cycloaddition reaction to a series of azides with excellent yields.This strategy for the obtention of clicked adducts of [60]fullerene is of special interest for biological applications

Cyclooctyne [60]fullerene hexakis adducts: a globular scaffold for copper-free click chemistry

The synthesis of a new highly symmetric hexakis adduct of C60 appended with 12 cyclooctyne moieties has been carried out. This compound has been used for the copper-free strain-promoted cycloaddition reaction to a series of azides with excellent yields. This strategy for the obtention of clicked adducts of [60]fullerene is of special interest for biological applicationsEuropean Research Council ERC-320441-Chir all carbonMinisterio de Economía y Competitividad CTQ2014-52045-R, CTQ2014-52328-PComunidad Autónoma de Madrid S2013/MIT-28

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2–advanced breast cancer: GEICAM/2014–12 (FLIPPER)

Background The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. Patients and methods In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. Results In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36–0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37–0.64, P = 0.001). The most frequent grade 3–4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3–4 adverse event was fatigue (4.3% vs. 0%). Conclusions Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients

Alteraciones metabólicas secundarias al tratamiento con inhibidores de proteasa en pacientes infectados por el Virus de la Inmunodeficiencia Humana.

INTRODUCCIÓN: Los niños infectados por el VIH son más susceptibles de sufrir los efectos adversos del tratamiento, particularmente de los inhibidores de proteasa, debido al mecanismo de transmisión y las numerosas exposiciones a diferentes esquemas desde su nacimiento. OBJETIVOS: Determinar los efectos metabólicos a corto y a medio plazo del tratamiento con terapia antiretroviral altamente activa (TARAA), causados principalmente por los Inhibidores de proteasa (IP) en los pacientes pediátricos VIH seguidos de manera ambulatoria por unidades especializadas. METODOLOGÍA: Estudio descriptivo y analítico, retrospectivo y transversal, en el que se incluyen pacientes infectados por VIH, sin condicionantes de SIDA y bajo tratamiento antirretroviral combinado, seguidos en consultas de Infectología Pediátrica del Hospital Infantil Universitario Miguel Servet de Zaragoza, vistos en consulta desde el período de febrero de 2017 hasta julio de 2018. RESULTADOS: El 66,7% de los niños tratados con IP en el momento actual presenta cifras de colesterol, LDL y triglicéridos por encima de los valores de normalidad frente al 20%, 6.7% y 6.7% respectivamente, de los niños tratados sin IP. La disminución de cifras de colesterol, LDL y triglicéridos obtenida en analíticas durante y tras el tratamiento con IP en un mismo paciente, ha resultado estadísticamente significativa (p<0,05). La superioridad de cifras de colesterol, LDL y triglicéridos obtenida en analíticas de pacientes tratados con IP frente a valores obtenidos de pacientes tratados sin IP, ha resultado estadísticamente significativa (p<0,05). CONCLUSIONES: Es complicado atribuir a cada fármaco su correspondiente implicación en las diferentes alteraciones metabólicas. Sin embargo, de forma general podría decirse que los IP son los principales responsables de la dislipemia objetivada en sangre.<br /

Physical literacy in older adults : a scoping review protocol

Population aging is a prominent phenomenon worldwide. The increase in physical inactivity and co-morbid diseases poses a major challenge to current community health policies. Physical activity guidelines recommended for older people have not been met by this population group. For this reason, a new model, physical literacy, is being innovated and has gained global attention and has emerged as an effective and innovative active aging strategy to improve physical activity participation of this vulnerable group. However, the evidence on physical literacy in the older adult so far is brief and diffuse. Therefore, the aim was to conduct a scoping review protocol to identify and map physical literacy in older people. This scoping review protocol was based on the Joanna Briggs Institute Method. The search will be performed on Embase, IBSS ProQuest, Medline OVID, PsycINFO Ebsco, PubMed, ScienceDirect, Scopus, SPORTDiscus, Social Services Abstracts ProQuest, Sociological Abstracts ProQuest, Web of Science ISI, Wiley Online Library, Cochrane Library, and ERIC Ebsco databases. All types of studies published since 2001 in English, Spanish, and Portuguese examining physical literacy over the lifespan of older adults were included. Two independent reviewers will organize and select studies according to the objectives and questions of the scoping review. The selected publications will be organized and summarized using a checklist proposed by the PRISMA- ScR. Qualitative data analysis (thematic analysis) will be performed to identify meanings and patterns to answer the research question. The final scoping review will present the main evidence available, key concepts/definitions, research conducted, and knowledge gaps related to physical literacy in older adults, leading to strategies to improve the community health of this population, as well as health literacy.info:eu-repo/semantics/publishedVersio

Clinical and economic impact of ‘ROS1-testing’ strategy compared to a ‘no-ROS1-testing’ strategy in advanced NSCLC in Spain

Background Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. Methods A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (euro 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. Results A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to euro 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 euro/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. Conclusions Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients

Discovery of the first dual GSK3 beta inhibitor/Nrf2 inducer. A new multitarget therapeutic strategy for Alzheimer's disease

The formation of neurofibrillary tangles (NFTs), oxidative stress and neuroinflammation have emerged as key targets for the treatment of Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder. These pathological hallmarks are closely related to the over-activity of the enzyme GSK3β and the downregulation of the defense pathway Nrf2-EpRE observed in AD patients. Herein, we report the synthesis and pharmacological evaluation of a new family of multitarget 2,4-dihydropyrano[2,3-c]pyrazoles as dual GSK3β inhibitors and Nrf2 inducers. These compounds are able to inhibit GSK3β and induce the Nrf2 phase II antioxidant and anti-inflammatory pathway at micromolar concentrations, showing interesting structure-activity relationships. The association of both activities has resulted in a remarkable anti-inflammatory ability with an interesting neuroprotective profile on in vitro models of neuronal death induced by oxidative stress and energy depletion and AD. Furthermore, none of the compounds exhibited in vitro neurotoxicity or hepatotoxicity and hence they had improved safety profiles compared to the known electrophilic Nrf2 inducers. In conclusion, the combination of both activities in this family of multitarget compounds confers them a notable interest for the development of lead compounds for the treatment of AD

An implantation Diamond detector as a beam monitor for an intense radioactive ion beam

We present the characterization of a Diamond detector and its response as a beam rate monitor with full stopping of radioactive ion beams of high intensity. The detector has been implemented in the VAMOS focal plane at GANIL and utilised in conjunction with AGATA and MUGAST detector systems. In the present experiment, for the first time, the beam has been fully stopped, rather than being recorded by a transmission detector. The Diamond detector has been tested for use as a particle counter for monitoring a high intensity, radioactive ion beam in the study of the alpha transfer reaction 7Li(15O,t)19Ne. The present experiment, which took place in July 2019, has used a 15O radioactive beam with a high intensity of 107 particles per second due to the weak reaction population and it has been measured using the VAMOS spectrometer and the AGATA and MUGAST arrays. Detailed monitoring of beam intensities in the range of 106 – 107 particles per second is particularly challenging in radioactive ion beam experiments. Thus, the chosen method involves the diamond detector due to its sub-nanosecond response time as well as its radiation hardness. The study of the alpha transfer reaction 7Li(15O,t)19Ne will be performed to determine the radiative alpha capture rate on 15O which is a key breakout route from the Hot-CNO cycle which leads to a explosive nucleosynthesis in X-ray bursts