Can Exercise Make You Smarter, Happier, and Have More Neurons? A Hormetic Perspective

Exercise can make you smarter, happier and have more neurons depending on the dose (intensity) of the training program. It is well recognized that exercise protocols induce both positive and negative effects depending on the intensity of the exercise, among other key factors, a process described as a hormetic-like biphasic dose-response. However, no evidences have been reported till very recently about the biphasic response of some of the potential mediators of the exercise-induced actions. This hypothesis and theory will focus on the adult hippocampal neurogenesis (AHN) as a putative physical substrate for hormesis responses to exercise in the context of exercise-induced actions on cognition and mood, and on the molecular pathways which might potentially be mediating these actions.The authors acknowledge the support of CSIC (Spanish Council for Scientific Investigation) and the Ministerio de Economía y Competitividad, Spain (research grant reference BFU2013-48907-R).Peer reviewedPeer Reviewe

Relating the Kick Velocities of Young Pulsars with Magnetic Field Growth Timescales Inferred From Braking Indices

A nascent neutron star may be exposed to fallback accretion soon after the proto-neutron star stage. This high accretion episode can submerge the magnetic field deep in the crust. The diffusion of the magnetic field back to the surface will take hundreds to millions of years depending on the amount of mass accreted and the consequent depth the field is buried. Neutron stars with large kick velocities will accrete less amount of fallback material leading to shallower submergence of their fields and shorter time-scales for the growth of their fields. We obtain the relation $\tau_{\rm Ohm} \propto v^{-1}$ between the space velocity of the neutron star and Ohmic time-scale for the growth of the magnetic field. We compare this with the relation between the measured transverse velocities, $v_{\perp}$ and the field growth time-scales, $\mu/\dot{\mu}$, inferred from the measured braking indices. We find that the observational data is consistent with the theoretical prediction though the small number of data precludes a strong conclusion. Measurement of the transverse velocities of pulsars B1509$-$58, J1846$-$0258, J1119$-$6127 and J1734$-$3333 would increase the number of the data and strongly contribute to understanding whether pulsar fields grow following fallback accretion.Comment: Accepted to MNRAS Letters. Title and abstract are change

The near-infrared detection of PSR B0540-69 and its nebula

The ~1700 year old PSR B0540-69 in the LMC is considered the twin of the Crab pulsar because of its similar spin parameters, magnetic field, and energetics. Its optical spectrum is fit by a power-law, ascribed to synchrotron radiation, like for the young Crab and Vela pulsars. nIR observations, never performed for PSR B0540-69, are crucial to determine whether the optical power-law spectrum extends to longer wavelengths or a new break occurs, like it happens for both the Crab and Vela pulsars in the mIR, hinting at an even more complex particle energy and density distribution in the pulsar magnetosphere. We observed PSR B0540-69 in the J, H, and Ks bands with the VLT to detect it, for the first time, in the nIR and characterise its optical-to-nIR spectrum. To disentangle the pulsar emission from that of its pulsar wind nebula (PWN), we obtained high-spatial resolution adaptive optics images with NACO. We could clearly identify PSR B0540-69 in our J, H, and Ks-band images and measure its flux (J=20.14, H=19.33, Ks=18.55, with an overall error of +/- 0.1 magnitudes in each band). The joint fit to the available optical and nIR photometry with a power-law spectrum gives a spectral index alpha=0.70 +/-0.04. The comparison between our NACO images and HST optical ones does not reveal any apparent difference in the PWN morphology as a function of wavelength. The PWN optical-to-nIR spectrum is also fit by a single power-law, with spectral index alpha=0.56+/- 0.03, slightly flatter than the pulsar's. Using NACO at the VLT, we obtained the first detection of PSR B0540-69 and its PWN in the nIR. Due to the small angular scale of the PWN (~4") only the spatial resolution of the JWST will make it possible to extend the study of the pulsar and PWN spectrum towards the mid-IR.Comment: 11 pages, 10 figures, Accepted for publication on Astronomy and Astrophysic

Role of Smad2 in the processes of neuroplasticity related to hippocampal-dependent spatial learning and memory

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 30-03-2017Esta tesis tiene embargado el acceso al texto completo hasta el 30-09-201

Physical-Mechanical Modifications of Eggs for Food-Processing During Storage

Abstract Physical-mechanical properties of egg constituents and their modifications during storage and poststorage greatly influence the efficiency of food processing, such as the separation of white and yolk by mechanical shelling. Thick albumen height, Haugh unit, yolk index and vitelline membrane-yolk system strength of eggs from Hy-Line White and Lohmann Brown hens were analyzed during 7 mo of storage at 0°C performing 3 poststorage treatments: i) immediately after refrigeration, T1; ii) after a further 6 h at 18°C after refrigeration, T2; and iii) after a week at 18°C after refrigeration, T3. For all qualitative parameters considered, this last poststorage treatment appeared to be the factor that produced the highest decrements; with respect to the first poststorage treatment, a further week at 18°C after refrigeration can involve mean decreases of about 19, 14, 14, and 16% in thick albumen height, Haugh unit, yolk index, and vitelline membrane-yolk system strength (in terms of maximum force), respectively. During about 7 mo of storage at 0°C, the latter parameter decreases, on average, by 10%. Increasing the storage time, physical-mechanical behavior was sometimes divergent from the observed trends

Meta-Analysis Design and Results in Real Life: Problem Solvers or Detour to Maze. A Critical Review of Meta-Analysis of DAPT Randomized Controlled Trials.

Therapeutic strategies - such as duration of dual antiplatelet therapy after coronary artery stenting - usually generate a large quantity of meta-analyses. The meta-analyses that include the same randomized clinical trials should produce similar results. Our aim in the study is to analyze the quality and to compare the results of meta-analyses focused on a controversial topic such as dual antiplatelet therapy after percutaneous coronary intervention. We searched all published meta-analyses published up to November 2015 (near DAPT trial publication) selecting those that included the same randomized clinical trials comparing patterns of briefer versus longer-term double antiplatelet therapy. Seventeen meta-analyses achieved our selection criteria. Of the seventeen analyzed, we identified seven (41.1%) based on the same ten randomized clinical trials (RCTs), yet their results varied widely. Many of the meta-analyses differed in only some minor aspect of the design (i.e. eligible studies, length of comparators and statistical methods used). Some authors differed in the number of patients participating in RCTs and even, despite reviewing the same underlying trials, only 2 of the 7 meta-analyses included the same number of patients. Meta-analyses around cardiovascular, all-cause or non-cardiovascular death differ frequently. In the DAPT duration setting, several meta-analyses have been recently published based on the same data, presenting several issues making it difficult to determine clear recommendations on certain points.IN receives research funding from Astrazeneca; has received minor consulting fees from Boston, Medtronic, Astrazeneca; and speaking fees or support for attending scientificmeetings fromBoehringer, Daiichi-Sankyo, Lilly, AstraZeneca and Pfizer. AE is Astrazeneca employee. HB receives research funding from the Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, BMS, Janssen and Novartis; has received consulting fees from Abbott, AstraZeneca, Bayer, BMS-Pfizer, Novartis; and speaking fees or support for attending scientificmeetings from AstraZeneca, Bayer, BMS-Pfizer, Ferrer, Novartis, Servier and MEDSCAPE-the heart.og. The other authors pose no relevant disclosures regarding this manuscript.S

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, revealed cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis

The optical light curve of the LMC pulsar B0540-69 in 2009

This paper reports a detailed analysis of the optical light curve of PSR B0540-69, the second brightest pulsar in the visible band, obtained in 2009 (Jan. 18 and 20, and Dec. 14, 15, 16, 18) with the very high speed photon counting photometer Iqueye mounted at the ESO 3.6-m NTT in La Silla (Chile). The optical light curve derived by Iqueye shows a double structure in the main peak, with a raising edge steeper than the trailing edge. The double peak can be fitted by two Gaussians with the same height and FWHM of 13.3 and 15.5 ms respectively. Our new values of spin frequencies allow to extend by 3.5 years the time interval over which a reliable estimate of frequency first and second derivatives can be performed. A discussion of implications on the braking index and age of the pulsar is carried out. A value of n = 2.087 +/- 0.007 for the overall braking index from 1987 to 2009 is derived. The braking index corrected age is confirmed around 1700 years.Comment: Accepted for publication in MNRA

Cost-effectiveness of sodium zirconium cyclosilicate for the treatment of hyperkalemia in patients with chronic kidney disease or heart failure in Spain

[Resumen] Antecedentes y objetivo. La hiperpotasemia (HK) es una alteración electrolítica en la concentración de iones potasio (K+), cuyo riesgo aumenta en pacientes con enfermedad renal crónica (ERC) o insuficiencia cardiaca (IC) y/o en pacientes en tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA). Los nuevos quelantes orales de K+ ofrecen un tratamiento seguro y eficaz para mantener la normopotasemia en estos pacientes. El objetivo del análisis es estimar el coste-efectividad del ciclosilicato de sodio y zirconio (CSZ) para el tratamiento de la HK crónica en pacientes con ERC o IC vs. tratamiento estándar (poliestireno sulfonato cálcico y modificaciones del estilo de vida) desde la perspectiva del Sistema Nacional de Salud (SNS) español. Materiales y métodos. Se utilizaron dos modelos de microsimulación que reflejan la historia natural de la ERC y de la IC. En ambos modelos se realizó una simulación de forma individual de los niveles de K+. Con base en la eficacia (reducción de los niveles de K+), la calidad de vida de los pacientes (utilidades según estado de salud, y disutilidades de los eventos derivados de cada patología y los eventos adversos [EA] del tratamiento) y a los costes contemplados (coste del tratamiento para la HK, del tratamiento con iSRAA y su modificación, de los estados de salud, del manejo de los eventos derivados de cada patología, de los episodios de HK, y de los EA del tratamiento) (€, 2022), se obtuvieron resultados de beneficio clínico (años de vida ajustados por calidad [AVAC]) y costes. Se empleó un horizonte temporal de toda la vida del paciente y se aplicó una tasa de descuento del 3% para costes y resultados. Resultados. El CSZ resulta una opción más efectiva en ambas patologías, con una diferencia de AVAC de 0,476 en ERC, y de 0,978 en IC vs. tratamiento estándar, y supone un coste incremental de 3.616 € y 14.749 €, respectivamente, obteniéndose un ratio coste-utilidad incremental (RCUI) de 7.605 €/AVAC en ERC y 15.078 €/AVAC en IC. Conclusiones. El CSZ es una alternativa con una buena relación coste-efectividad para el tratamiento de la HK en pacientes con ERC o IC, teniendo en cuenta los valores de eficiencia de referencia empleados habitualmente en España.[Abstract] Background and objective. Hyperkalemia (HK) is an electrolyte disturbance in the concentration of potassium ions (K+), whose risk increases in patients with chronic kidney disease (CKD) or heart failure (HF) and/or in patients being treated with renin-angiotensin-aldosterone system inhibitors (RAASi). The new oral K+ chelators offer a safe and effective treatment to maintain normokalemia in these patients. The objective of the analysis is to estimate the cost-effectiveness of sodium zirconium cyclosilicate (SZC) for the treatment of chronic HK in patients with CKD or HF versus standard treatment (calcium polystyrene sulfonate and lifestyle modifications) from the perspective of the Spanish National Health System. Materials and methods. Two microsimulation models reflecting the natural history of CKD and HF were used. In both models, K+ levels were simulated individually. Based on efficacy (reduction of K+ levels), quality of life of patients (utilities according to health states, and disutilities of events derived from each pathology and adverse events [AEs] of treatment) and costs considered (cost of treatment for HK, of RAASi treatment and its modification, health states, management of events derived from each pathology, HK episodes, and AEs treatment) (€, 2022), clinical benefit (quality-adjusted life years [QALYs]) and cost results were obtained. A time horizon of the patient's lifetime was used and a discount rate of 3% was applied for costs and outcomes. Results. SZC is a more effective option in both pathologies, with a difference in QALYs of 0.476 in CKD and 0.978 in HF compared to standard treatment, and it represents an incremental cost of € 3,616 and € 14,749, respectively, obtaining an incremental cost-utility ratio of € 7,605 /QALY in CKD and € 15,078 /QALY in HF. Conclusions. SZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain

Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain.

A decrease in adult hippocampal neurogenesis has been linked to age-related cognitive impairment. However, the mechanisms involved in this age-related reduction remain elusive. Glucocorticoid hormones (GC) are important regulators of neural stem/precursor cells (NSPC) proliferation. GC are released from the adrenal glands in ultradian secretory pulses that generate characteristic circadian oscillations. Here, we investigated the hypothesis that GC oscillations prevent NSPC activation and preserve a quiescent NSPC pool in the aging hippocampus. We found that hippocampal NSPC populations lacking expression of the glucocorticoid receptor (GR) decayed exponentially with age, while GR-positive populations decayed linearly and predominated in the hippocampus from middle age onwards. Importantly, GC oscillations controlled NSPC activation and GR knockdown reactivated NSPC proliferation in aged mice. When modeled in primary hippocampal NSPC cultures, GC oscillations control cell cycle progression and induce specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. Finally, in a mouse model of accelerated aging, we show that disruption of GC oscillations induces lasting changes in dendritic complexity, spine numbers and morphology of newborn granule neurons. Together, these results indicate that GC oscillations preserve a population of GR-expressing NSPC during aging, preventing their activation possibly by epigenetic programming through methylation of specific gene promoters. Our observations suggest a novel mechanism mediated by GC that controls NSPC proliferation and preserves a dormant NSPC pool, possibly contributing to a neuroplasticity reserve in the aging brain