The health from the humanist perspective of Blas Álvarez de Miraval

A pesar de que existen diferentes estudios en las Ciencias de la Actividad Física y del Deporte sobre autores humanistas, el objetivo del presente trabajo es poner en valor la obra de una de las figuras más importantes del humanismo español, Blas Álvarez de Miraval, insigne médico y teólogo, a través del análisis pormenorizado de su obra cumbre, titulada De la conservación de la salud del cuerpo y el alma, cuyos resultados arrojan una visión única y diferente de lo que ha de ser la conservación de la salud desde una perspectiva integral por parte del individuoIn spite of the fact that there are different studies in the Sciences of the Sport on humanist authors, the aim of the present work is to put of relevancy the work of one of the most important figures of the Spanish humanism, Blas Álvarez de Miraval, celebrated doctor and theologian, with regard to the Sciences of the Physical Activity and of the Sport by means of the study detailed of his greatest work, "Of the conservation of the health of the body and the soul", which results throw an only and different vision from what has to be the conservation of the health from the integral care of the individua

Lamivudine plus a boosted-protease inhibitor as simplification strategy in HIV-infected patients with toxicity to nucleoside analogues

Purpose of the study: Dual therapy with lamivudine plus a PI boosted with ritonavir (PI/r) could be an alternative to standard triple therapy or PI/r monotherapy as a simplification strategy in patients with toxicity to nucleoside analogues (NA). Methods: Retrospective cohort study of 44 HIV-infected patients on suppressive HAART, with no chronic HBV, who simplified to this dual therapy since 2008. Virological and immunological outcome, lipids and renal changes were evaluated. Summary of results: Mean age was 50 years (38-70), 66% were male, and the median time of HIV infection was 18.6 years. The median nadir CD4+ count was 150 cells/ml (2–407). At inclusion, patients were receiving therapy with lamivudine plus atazanavir/r in 5 cases, lopinavir/r in 12, and darunavir/r in 27, and they had an HIV RNA level<50 copies/ml for a median time of 794 days (129–2344, 90% >6 months). The NA discontinued was tenofovir (27), didanosine (12), AZT (3), and d4T (2). The reasons for changing were toxicity in 76% of cases, especially renal impairment. They had received a mean of 8 regimens before (2–20), and 55% were in CDC-stage C. In 11 cases, history of resistance was available (to NA in 7 cases, including the 210W mutation in four). The mutations 184V was not observed, but four patients (9%) had a previous failure to therapy including 3tC. Mutations in the protease gene were observed in 8 patients (2 to 7 mutations, the most frequent 77I and 93L), without resistance to the current PI/r. During 62.8 patient-years of follow-up (median, 802 days), only 2 patients failed (4.5%), due to incomplete adherence, at 27 and 141 days. Of note, these two patients had no previous failed with 3tC or PI. Overall, CD4+ count increased for 55 cells/ml. No new adverse events were observed, but total cholesterol (from 180 to 246 mg/dl, p=0.007) and triglycerides (from 166 to 195, p=0.01) increased during the first 24 weeks with improvement at 48 weeks. On the other hand, estimated glomerular filtration rate improved during follow up (from 74.2 ml/min to 83.08 ml/min after 48 weeks, p=0.1). Conclusions: Dual therapy with lamivudine plus a boosted PI is safe and effective as simplification strategy in patients with toxicity to NA. This combination could be an alternative to mono or triple therapy in hard to treat patients, although an initial increase in lipid parameters could be observed

Secondary hyperparathyroidism in HIV-infected patients: relationship with bone remodeling and response to vitamin D supplementation

Purpose of the study: Secondary hyperparathyroidism (SH) is frequent in HIV-infected patients. However, the causes and consequences are not well established. The aim of our study was to determine the relationship between parathyroid hormone (PTH), vitamin D and bone mineral density (BMD) in HIV-infected patients, and the effect of vitamin D replacement on PTH levels. Methods: Prospective study of 506 patients with at least two sequential serum determinations of PTH and 25-hydroxyvitamin D levels. In all cases, a bone dual X-ray absorptiometry (DEXA) was performed at inclusion. Hyperparathyroidism was defined as a PTH level above 65 pg/ml. Summary of results: Mean age was 44 yrs (24–78), and 75% were male. Mean BMI was 23.7 (17.97–33.11), and only 3% were of black race. Median nadir CD4+ was 200 cells/µL (9–499), and median time of HIV infection was 15.3 yrs (1.7–25.2). At inclusion, 488 patients (86%) were on HAART (31% TDF+PI, 44% TDF+NNRTI, 25% non-TDF based regimen) for a median of 929.5 days (154–1969), and 40% were HCV-coinfected. Median eGFR was 97.9 ml/min (62.14–134.08). Overall, mean serum PTH was 56.3 pg/mL (27.2–95.07). SH was observed in 27% of cases, with a marked influence of seasonality (from 44% in January to 10% in August). Mean levels of vitamin D were 17.45 ng/mL (7.6–40.78), with 16% below 10 ng/ml, 59%<20 ng/ml (deficiency), 85%<30 ng/ml (insufficiency). SH was related to vitamin D deficiency (relative risk, RR, 2.44), age (RR 1.04 per year), and a higher decrease in eGFR (RR 1.03 per ml/min), after adjustment by season, antiretroviral therapy, GFR at baseline, and HCV coinfection. DEXA scan showed 18% osteoporosis and 54% osteopenia, and there was an inverse correlation between PTH levels and T and Z score in femoral neck (r=−0.14, p<0.01), higher in those patients below 40 yrs. Vitamin D supplementation in 181 patients produced a significant decrease in serum PTH (57.2 if not treated vs 50.5 pg/ml, p=0.02, 23% continues with SH) and the only factor associated with lack of response was persistent vitamin D deficiency. Conclusion: SH is relatively frequent in HIV patients, in close relation with vitamin D deficiency. It is associated with bone resorption, especially in the femoral neck. The use of vitamin D supplementation improves SH when levels above 20 ng/ml are achieved

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group:median change in (Delta) LVIDDN -0.06 (IQR:-0.15 to + 0.02), P < 0.0001, and LA:Ao -0.08 (IQR:-0.23 to + 0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo

A model for high-mass microquasar jets under the influence of a strong stellar wind

Context. High-mass microquasars (HMMQs) are systems from which relativistic jets are launched. At the scales of several times the binary system size, the jets are expected to follow a helical path caused by the interaction with a strong stellar wind and orbital motion.Such a trajectory has its influence on the non-thermal emission of the jets, which also depends strongly on the observing angle due to Doppler boosting effects. Aims. We explore how the expected non-thermal emission of HMMQ jets at small scales is affected by the impact of the stellar wind and the orbital motion on the jet propagation. Methods. We studied the broadband non-thermal emission, from radio to gamma rays, produced in HMMQ jets up to a distance of several orbital separations, taking into account a realistic jet trajectory, different model parameters, and orbital modulation. The jet trajectory is computed by considering momentum transfer with the stellar wind. Electrons are injected at the position where a recollimation shock in the jets is expected due to the wind impact. Their distribution along the jet path is obtained assuming local acceleration at the recollimation shock, and cooling via adiabatic, synchrotron, and inverse Compton processes. The synchrotron and inverse Compton emission is calculated taking into account synchrotron self-absorption within the jet, free-free absorption with the stellar wind, and absorption by stellar photons via pair production. Results. The spectrum is totally dominated by the jet over the counter-jet due to Doppler boosting. Broadband emission from microwaves to gamma rays is predicted, with radio emission being totally absorbed. This emission is rather concentrated in the regions close to the binary system and features strong orbital modulation at high energies. Asymmetric light curves are obtained owing to the helical trajectory of the jets. Conclusions. The presence of helical shaped jets could be inferred from asymmetries in the light curves, which become noticeable only for large jet Lorentz factors and low magnetic fields. Model parameters could be constrained if accurate phase-resolved lightcurves from GeV to TeV energies were available. The predictions for the synchrotron and the inverse Compton radiation are quite sensitive of the parameters determining the wind-jet interaction structure

Gamma-ray emission from interactions between jets and BLR clouds

Blazars -active galactic nuclei with a jet pointing towards the observer- are the most numerous γ-ray sources detected until date. In this work we show preliminary results of a model in which broad-line region (BLR) clouds penetrate in the jet, producing shocks capable of accelerating relativistic electrons; these electrons emit γ-rays when they interact with the photons coming from the BLR clouds. We calculate semi-analytically the dynamical evolution of a typical cloud inside the jet, the energy distribution of the locally accelerated electrons, and the high-energy emission the latter produce, taking into account relativistic effects. We estimate the dutycycle of these interactions in order to find whether they occur as discrete events or almost continuous. We compare the observed γ-ray fluxes with the ones predicted by our model and discuss the implications in terms of particle acceleration efficiency and mass-loading in the blazar jets

Gamma rays from jets interacting with BLR clouds in blazars

Context. The innermost parts of powerful jets in active galactic nuclei are surrounded by dense, high-velocity clouds from the broad-line region, which may penetrate into the jet and lead to the formation of a strong shock. Such jet-cloud interactions are expected to have measurable effects on the γ-ray emission from blazars. Aims. We characterise the dynamics of a typical cloud-jet interaction scenario, and the evolution of its radiative output in the 0.1-30 GeV energy range, to assess to what extent these interactions can contribute to the γ-ray emission in blazars. Methods. We use semi-analytical descriptions of the jet-cloud dynamics, taking into account the expansion of the cloud inside the jet and its acceleration. Assuming that electrons are accelerated in the interaction and making use of the hydrodynamical information, we then compute the high-energy radiation from the cloud, including the absorption of γ-rays in the ambient photon field through pair creation. Results. Jet-cloud interactions can lead to significant γ-ray fluxes in blazars with a broad-line region (BLR), in particular when the cloud expansion and acceleration inside the jet are taken into account. This is caused by 1) the increased shocked area in the jet, which leads to an increase in the energy budget for the non-thermal emission; 2) a more efficient inverse Compton cooling with the boosted photon field of the BLR; and 3) an increased observer luminosity due to Doppler boosting effects. Conclusions. For typical broad-line region parameters, either (i) jet-cloud interactions contribute significantly to the persistent γ-ray emission from blazars or (ii) the BLR is far from spherical or the fraction of energy deposited in non-thermal electrons is smal

Non-thermal emission from star-forming galaxies detected in gamma rays

Star-forming galaxies (SFGs) emit non-thermal radiation from radio to gamma-rays. We aim to investigate the main mechanisms of global CR transport and cooling in SFGs. The way they contribute in shaping the relations between non-thermal luminosities and SFR could shed light onto their nature. We develop a model to compute the CR populations of SFGs, taking into account their production, transport, and cooling. The model is parameterised only through global galaxy properties, and describes the non-thermal emission in both radio and gamma-rays. We focus on the role of diffusive and advective transport by galactic winds, either driven by turbulent or thermal instabilities. We compare model predictions to observations, for which we compile a homogeneous set of luminosities in these radio bands, and update those available in gamma-rays. Our model reproduces reasonably well the observed relations between the gamma-ray or 1.4 GHz radio luminosities and the SFR, assuming a single power-law scaling of the magnetic field with the latter with index beta=0.3, and winds blowing either at Alfvenic speeds or typical starburst wind velocities. Escape of CR is negligible for > 30 Mo/yr. A constant ionisation fraction of the interstellar medium fails to reproduce the 150 MHz radio luminosity throughout the whole SFR range. Our results reinforce the idea that galaxies with high SFR are CR calorimeters, and that the main mechanism driving proton escape is diffusion, whereas electron escape also proceeds via wind advection. They also suggest that these winds should be CR or thermally-driven at low and intermediate SFR, respectively. Our results globally support that magnetohydrodynamic turbulence is responsible for the dependence of the magnetic field strength on the SFR and that the ionisation fraction is strongly disfavoured to be constant throughout the whole SFR range.Comment: Submitted to Astronomy & Astrophysics (on 12/05/2021

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial

Background: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. Animals: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >= 1.6, normalized left ventricular internal diameter in diastole >= 1.7, and vertebral heart sum >10.5. Methods: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. Results: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). Conclusions and Clinical Importance: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit