Health-related quality of life and mortality in the ‘Seguimiento Universidad de Navarra’ prospective cohort study

This project was made possible by funding from the Spanish Government- Instituto de Salud Carlos III , and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658 , PI10/02293 , PI13/00615 , PI14/01668 , PI14/01798 , PI14/01764 , PI17/01795 , PI18/00631 , PI20/00564 and G03/140 ), from the Government of Navarra ( 27/2011 , 45/2011 , 122/2014 ), from the National Plan on Drugs ( 2020/021 ) as well as from the University of Navarra .Objective: To study the association between health-related quality of life (HRQoL) and all-cause mortality in a healthy middle-aged Mediterranean cohort. Methods: We included 15,390 participants –mean age 42.8 years at first HRQoL ascertainment, all university graduates–. HRQoL was assessed with the self-administered Medical Outcomes Study Short Form-36 (SF-36) twice, with a 4-year gap. We used multivariable-adjusted Cox regression models to address the relation between self-reported health and Physical or Mental Component Summary (PCS-36 or MCS-36) and mortality, and their interaction with prior comorbidities or adherence to the Mediterranean diet (MedDiet). Results: Over 8.7 years of median follow-up time, 266 deaths were identified. Hazard ratio (HR) for the excellent vs. poor/fair category in self-reported health was 0.30 (95 % confidence interval (CI), 0.16–0.57) in the model with repeated measurements of HRQoL. Both the PCS-36 (HRquartile4(Q4)vs.Q1 0.57 [95%CI, 0.36–0.90], ptrend < 0.001; HRper+10points: 0.64 [95%CI, 0.54–0.75]) and the MCS-36 (HRQ4vs.Q1 0.67 [95%CI, 0.46–0.97], ptrend = 0.025; HRper+10points: 0.86 [95%CI, 0.74–0.99]) were inversely associated with mortality in the model with repeated measurements of HRQoL. Previous comorbidities or adherence to the MedDiet did not modify these associations. Conclusions: Self-reported HRQoL –assessed as self-reported health, PCS-36 and MCS-36– obtained with the Spanish version of the SF-36 were inversely associated with mortality risk, regardless of the presence of previous comorbidities or adherence to the MedDiet.CIBER-OBN G03/140, PI10/02293, PI10/02658, PI13/00615, PI14/01668, PI14/01764, PI14/01798, PI17/01795, PI18/00631, PI20/00564Government-Instituto de Salud Carlos IIIHershey'sHarvard UniversityPlan Nacional sobre Drogas 2020/021 PNSDFederación Española de Enfermedades Raras RD 06/0045 FEDERUniversidad de Navarra 010830European Regional Development Fund ERDFGobierno de Navarra 122/2014, 27/2011, 45/201

Effects of caffeine supplementation on physical performance and mood dimensions in elite and trained-recreational athletes.

Background: Caffeine supplementation (CAFF) has an established ergogenic effect on physical performance and the psychological response to exercise. However, few studies have compared the response to CAFF intake among athletes of different competition level. This study compares the acute effects of CAFF on anaerobic performance, mood and perceived effort in elite and moderately-trained recreational athletes. Methods: Participants for this randomized, controlled, crossover study were 8 elite athletes (in the senior boxing national team) and 10 trained-recreational athletes. Under two experimental conditions, CAFF supplementation (6 mg/kg) or placebo (PLAC), the athletes completed a Wingate test. Subjective exertion during the test was recorded as the rating of perceived exertion (RPE) both at the general level (RPEgeneral) and at the levels muscular (RPEmuscular) and cardiorespiratory (RPEcardio). Before the Wingate test, participants completed the questionnaires Profiles of Moods States (POMS) and Subjective Vitality Scale (SVS). Results: In response to CAFF intake, improvements were noted in Wpeak (11.22 ± 0.65 vs 10.70 ± 0.84; p = 0.003; η2 p =0.44), Wavg (8.75 ± 0.55 vs 8.41 0.46; p = 0.001; η2 p =0.53) and time taken to reach Wpeak (7.56 ± 1.58 vs 9.11 ± 1.53; p < 0.001; η2 p =0.57) both in the elite and trained-recreational athletes. However, only the elite athletes showed significant increases in tension (+ 325%), vigor (+ 31%) and SVS (+ 28%) scores after the intake of CAFF compared to levels recorded under the condition PLAC (p < 0.05). Similarly, levels of vigor after consuming CAFF were significantly higher in the elite than the trained-recreational athletes (+ 5.8%). Conclusions: CAFF supplementation improved anaerobic performance in both the elite and recreational athletes. However, the ergogenic effect of CAFF on several mood dimensions and subjective vitality was greater in the elite athletes.post-print700 K

Health-related quality of life and mortality in the 'Seguimiento Universidad de Navarra' prospective cohort study

Objective: To study the association between health-related quality of life (HRQoL) and all-cause mortality in a healthy middle-aged Mediterranean cohort. Methods: We included 15,390 participants –mean age 42.8 years at first HRQoL ascertainment, all university graduates–. HRQoL was assessed with the self-administered Medical Outcomes Study Short Form-36 (SF-36) twice, with a 4-year gap. We used multivariable-adjusted Cox regression models to address the relation between self-reported health and Physical or Mental Component Summary (PCS-36 or MCS-36) and mortality, and their interaction with prior comorbidities or adherence to the Mediterranean diet (MedDiet). Results: Over 8.7 years of median follow-up time, 266 deaths were identified. Hazard ratio (HR) for the excellent vs. poor/fair category in self-reported health was 0.30 (95 % confidence interval (CI), 0.16–0.57) in the model with repeated measurements of HRQoL. Both the PCS-36 (HRquartile4(Q4)vs.Q1 0.57 [95%CI, 0.36–0.90], ptrend < 0.001; HRper+10points: 0.64 [95%CI, 0.54–0.75]) and the MCS-36 (HRQ4vs.Q1 0.67 [95%CI, 0.46–0.97], ptrend = 0.025; HRper+10points: 0.86 [95%CI, 0.74–0.99]) were inversely associated with mortality in the model with repeated measurements of HRQoL. Previous comorbidities or adherence to the MedDiet did not modify these associations. Conclusions: Self-reported HRQoL –assessed as self-reported health, PCS-36 and MCS-36– obtained with the Spanish version of the SF-36 were inversely associated with mortality risk, regardless of the presence of previous comorbidities or adherence to the MedDiet.This project was made possible by funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI18/00631, PI20/00564 and G03/140), from the Government of Navarra (27/2011, 45/2011, 122/2014), from the National Plan on Drugs (2020/021) as well as from the University of Navarra

Active interventions in hypercholeteroloemia patiens with high cardiovascular risk in primary care

Introduction: Hypercholesterolemia is a major modifiable risk factors for cardiovascular disease (CVD). Its reduction reduces morbidity and mortality from ischemic heart disease and CVD in general, primary prevention and secondary prevention especially. Objective: To determine whether a notarized and intensive clinical practice can overcome inertia and achieve the therapeutic goal (OT) LDL-C &lt;100 mg &lt;dL in high-risk patients attended in Primary Care (PC) in our country. Methodology: epidemiological, prospective, multicenter study conducted in centers of different ACs By AP consecutive sampling 310 patients at high cardiovascular risk (diabetic or established CVD) previously treated with statins, which did not reach the OT included c-LDL. Results: The study subjects had a mean age of 65.2 years, of which 60.32% were male. The 41.64% had a previous EVC, acute myocardial infarction (20.33%), angina (16.07%), stroke /TIA (9.19%), arthropathy (5.25%), diabetes (70 , 87%), hypertension (71.01%), and abdominal obesity (69.62%). The 43.57% (95% CI: 37,21; 50,08) of patients who performed the 2nd visit (241) got the OT. 62.50% (95% CI: 55.68, 68.98) of those who took the 3rd (216) got the OT. Finally, 77.56% (95% CI: 72.13, 83.08) patients who performed the last visit (205) got the OT. Throughout the study there was a reduction in LDL-C levels from 135.6 mg /dL at baseline, 107.4 mg /dL in the 2nd visit, 97.3 mg /dL in the 3rd visit, up to 90.7 mg /dL at the final visit (p &lt;0.0001) The increase in HDL-C from baseline (50.9 mg /dL) and final (53.6 mg /dL) was also significant (p = 0.013). Conclusions: The reassessment and intensification of treatment in patients at high cardiovascular risk treated in primary care, applying the indications of the guides, achieves the OT in more than three quarters of the previously uncontrolled within half a year. These results should encourage us to overcome the therapeutic inertia in the control of CVD by early and energetic performance against hypercholesterolemia.Introducción: La hipercolesterolemia es uno de los principales factores de riesgo modificables de la enfermedad cardiovascular (ECV). Su reducción disminuye la morbimortalidad por cardiopatía isquémica y ECV en general, en prevención primaria y en prevención secundaria especialmente. Objetivo: Comprobar si una práctica clínica protocolizada e intensiva permite vencer la inercia y alcanzar el objetivo terapéutico (OT) de c-LDL < 100 mg/dL en pacientes de alto riesgo asistidos en Atención Primaria (AP) de nuestro país. Metodología: Estudio epidemiológico, prospectivo, multicentrico, realizado en Centros de AP de diferentes CC.AA. Mediante muestreo consecutivo se incluyeron 310 pacientes de alto riesgo cardiovascular (diabéticos o con ECV establecida), tratados previamente con estatinas, que no alcanzaban el OT de c-LDL. Resultados: Los sujetos del estudio tenían una edad media de 65,2 años, de los que el 60,32% eran varones. El 41,64% presentaba un EVC previo, infarto agudo de miocardio (20,33%), angina (16,07%), ictus/AIT (9,19%), artropatía (5,25%), diabetes (70,87%), hipertensión (71,01%), y obesidad abdominal (69,62%). El 43,57% (IC95%: 37,21; 50,08) de los pacientes que realizaron la 2a visita (241) consiguieron el OT. El 62,50% (IC95%: 55,68; 68,98) de los que realizaron la 3a (216) consiguieron el OT. Finalmente, el 77,56% (IC95%: 72,13; 83,08) de los pacientes que realizaron la última visita (205) consiguieron el OT. A lo largo del estudio hubo una reducción de los niveles de c-LDL desde los 135,6 mg/ dL en la visita basal, 107,4 mg/dL en la 2a visita, 97,3 mg/ dL en la 3a visita, hasta los 90,7 mg/dL en la visita final (p < 0,0001) El incremento de c-HDL entre la visita basal (50,9 mg/dL) y la final (53,6 mg/dL) también fue significativo (p = 0,013). Conclusiones: La reevaluación e intensificación del tratamiento en pacientes de alto riesgo cardiovascular atendidos en Atención Primaria, aplicando las indicaciones de las guías, permite alcanzar el OT en más de las tres cuartas partes de los previamente no controlados en el plazo de medio año. Estos resultados nos deben estimular a superar la inercia terapéutica en el control de la ECV mediante una actuación precoz y enérgica ante la hipercolesterolemi

Viure amb càncer colorectal

Treballs d'Educació Farmacèutica als ciutadans. Unitat Docent d'Estades en Pràctiques Tutelades. Facultat de Farmàcia, Universitat de Barcelona. Curs: 2015-2016. Tutors: Jordi Casas Sánchez i Marian March Pujol

Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSALR mouse model and patient-derived myotubes. In HSALR, antagomiR-218 reached 40-60 pM 2weeks after injection, rescued molecular and functional phenotypes in a dose- and time-dependent manner, and showed a good toxicity profile after a single subcutaneous administration. In muscle tissue, antagomiR rescued the normal subcellular distribution of Mbnl1 and did not alter the proportion of myonuclei containing CUG foci. In patient-derived cells, antagomiR-218 improved defective fusion and differentiation and rescued up to 34% of the gene expression alterations found in the transcriptome of patient cells. Importantly, miR-218 was found to be upregulated in DM1 muscle biopsies, pinpointing this microRNA (miRNA) as a relevant therapeutic target.This work was funded by research grants from Instituto de Salud Carlos III, including funds from FEDER, to M.P.-A. and B.L. (PI17/00352) and HR17-00268 (TATAMI project) from the “la Caixa” Banking Foundation to R.A. I.G.-M. was funded by the Precipita Project titled “Desarrollo de una terapia innovadora contra la distrofia miotónica,” E.C.-H. and J.M.F.-C. were supported by the post-doctoral fellowships APOSTD/2019/142 and APOSTD/2017/088 from the Fondo Social Europeo for science and investigation, while J.E.-E. was the recipient of a Santiago Grisolia fellowship (Grisolip2018/098) from the Generalidad Valenciana. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020). Antibody MB1a (4A8) was provided by MDA Monoclonal Antibody Resource

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes

Effect of the haematocrit layer geometry on Plasmodium falciparum static thin-layer in vitro cultures

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>cultivation of <it>Plasmodium falciparum </it>is usually carried out through the continuous preservation of infected erythrocytes deposited in static thin layers of settled haematocrit. This technique, called the candle-jar method, was first achieved by Trager and Jensen in 1976 and has undergone slight modifications since then. However, no systematic studies concerning the geometry of the haematocrit layer have been carried out. In this work, a thorough investigation of the effects of the geometric culturing conditions on the parasite's development is presented.</p> <p>Methods</p> <p>Several experimental trials exploring different settings have been carried out, covering haematocrit layer depths that ranged from 6 mm to 3 mm and separation between the walls of the culturing device that ranged from 7.5 mm to 9 mm. The obtained results have been analysed and compared to different system-level models and to an Individual-Based Model.</p> <p>Conclusion</p> <p>In line with the results, a mechanism governing the propagation of the infection which limits it to the vicinity of the interface between the haematocrit layer and the culture medium is deduced, and the most appropriate configurations are proposed for further experimental assays.</p

The status of the Quijote multi-frequency instrument

The QUIJOTE-CMB project has been described in previous publications. Here we present the current status of the QUIJOTE multi-frequency instrument (MFI) with five separate polarimeters (providing 5 independent sky pixels): two which operate at 10-14 GHz, two which operate at 16-20 GHz, and a central polarimeter at 30 GHz. The optical arrangement includes 5 conical corrugated feedhorns staring into a dual reflector crossed-draconian system, which provides optimal cross-polarization properties (designed to be < -35 dB) and symmetric beams. Each horn feeds a novel cryogenic on-axis rotating polar modulator which can rotate at a speed of up to 1 Hz. The science driver for this first instrument is the characterization of the galactic emission. The polarimeters use the polar modulator to derive linear polar parameters Q, U and I and switch out various systematics. The detection system provides optimum sensitivity through 2 correlated and 2 total power channels. The system is calibrated using bright polarized celestial sources and through a secondary calibration source and antenna. The acquisition system, telescope control and housekeeping are all linked through a real-time gigabit Ethernet network. All communication, power and helium gas are passed through a central rotary joint. The time stamp is synchronized to a GPS time signal. The acquisition software is based on PLCs written in Beckhoffs TwinCat and ethercat. The user interface is written in LABVIEW. The status of the QUIJOTE MFI will be presented including pre-commissioning results and laboratory testing