Relación entre el uso de Internet y el rendimiento académico en una muestra de adolescentes canarios

El incremento en el número de ordenadores y conexiones a internet en los hogares canarios plantea la necesidad de analizar el tiempo y uso que se hace de internet en la adolescencia y su relación con el rendimiento escolar. 578 adolescentes respondieron a una entrevista semiestructurada sobre hábitos de consumo. Es frecuente es pasar 2 horas diarias “conectado” con diferencias significativas entre varones y mujeres. El tiempo de consumo se relaciona con el número de faltas a clase y el número de suspensos, pero no con el rendimiento en asignaturas como Lengua y Matemáticas.The increase in the number of computers and access to Internet in Canarian households suggests the necessity of studying the use that adolescents make of it, as well as its influence in their academic performance. 578 adolescents took part in a semi-structured interview on Internet use habits. The results showed that adolescents spend an average of two hours a day connected to Internet, with significant differences between males and females. The time invested in Internet is linked to the number of absences from school and subjects failed. However, there is no influence in the performance in subjects such as Linguistics and Maths

Field observations of wave and current characteristics on a microtidal reflective beach

At Costa Verde beach, Colombia, an intermediate reflective beach, the contributions of gravity (G) and infragravity (IG) waves to the evolution of the free surface and the cross-shore and alongshore velocities during two climatic periods were determined by applying the continuous wavelet transformation to sensor data recorded in field campaigns. In the dry season, the highest values of IG energy were found in the vicinity of the coastline, due to reflection processes in the área near the foreshore. Additionally, the cross-wavelet and coherence spectra between the free surface and the cross-shore and alongshore velocities allowed the identification of cross-shore and alongshore standing ‘‘leaky’’ waves and standing ‘‘edge’’ waves. In the rainy (wet) season, cross-shore and alongshore progressive leaky waves predominated in the área farthest from the shoreline. Close to the shore, mostly cross-shore standing leaky waves predominated because of reflection dynamics. On Costa Verde beach, the wave breaking is usually of the plunging type, which is characteristic of an intermediate reflective beach. The dimensionless fall velocity parameter (X) indicated that Costa Verde assumes the form of an intermediate ridge-runnel beach in the rainy (wet) season (low swell energy) and an intermediate transverse bar and rip beach in the dry season (high swell energy). This means that the Costa Verde beach tends to have small rip currents and pronounced ‘‘cusps.’’ Despite the lack of conclusive evidence to suggest that the appearance of cusps and rip currents is due to the presence of standing edge waves during the dry season, the data show that during the period of high energy swell, IG waves exist simultaneously with the cusps as small rhythmic systems of rip currents

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer

Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1-2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC

A virtual computer lab for distance biomedical technology education

educatio

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe

A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis

This work was partially supported by the CENIT program from the Centro Tecnológico Industrial (CEN-20091016), grants from the Spanish Institute of Health Carlos III (ADE10/00026, PI09/02444, PI12/00511, Acción Transversal de Cáncer) grants from the Fondo de Investigacion Sanitaria/FEDER (08/1276, 08/0024, PS09/02368, 11/00219, 11/00681), and by COST office through COST action BM1206. SCB is supported by contracts from the Fondo de Investigación Sanitaria (CP 03-0070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Centro Tecnológico IndustrialInstituto de Salud Carlos IIIFondo de Investigación Sanitaria / FEDE

Sphingosine 1-phosphate receptor 4 promotes nonalcoholic steatohepatitis by activating NLRP3 inflammasome

BACKGROUND & AIMS: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear. METHODS: We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n-octylphenyl)ethyl]-1,3-propanediol hydrochloride)-like sphingolipid-focused library. RESULTS: The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4(++/-) mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca++ release and deactivated the Nod-like receptor pyrin domaincontainning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate-receptor-dependent [Ca++] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4(+/-) mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome. CONCLUSIONS: S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages

Fractionation of eucalyptus globulus wood by glycerol-water pretreatment: optimization and modeling

A glycerol-organosolv process can be a good alternative for Eucalyptus wood fractionation into its main compounds, improving the enzymatic saccharification of the cellulose. A study of process variables - glycerol−water percent content, temperature, and process time - was carried out using a Box-Behnken experimental design. The cellulose obtained from pretreated solids was recovered almost quantitatively, leading to a solid with a high percentage of cellulose (77 g/100 g of pretreated solid), low lignin content (9 g/100 g of pretreated solid), and 18% of residual hemicellulose in the solid at 200 °C, 56% of glycerol−water and 69 min. The enzymatic saccharification was enhanced achieving 98% cellulose-to-glucose conversion (under conditions: liquid to solid ratio 20 g/g and enzyme loading 20 FPU/g of solid). This study contributes to the improvement of biomass fractionation by exploring an eco-friendly treatment which allows for almost complete wood fractionation into constituents and high levels of glucose recovery available for subsequent yeast fermentation to bioethanol.The authors A. Romani and F. B. Pereira thank to the Portuguese Foundation for Science and Technology (FCT, Portugal) for their fellowships (grant number: SFRH/BPD/77995/2011 and SFRH/BD/64776/2009, respectively)