Terapia celular “neuro-restauradora” en la enfermedad de Parkinson: un debate pendiente

Existe en la actualidad un gran entusiasmo sobre las perspectivas derivadas de la denominada terapia celular en la enfermedad de Parkinson. Este entusiasmo ha sobrepasado la esfera de la comunidad médica, llegando hasta el público general, y se ha venido alimentando de un considerable debate ético y político, hurtándose en todo momento la necesidad de un análisis realmente científico sobre las cualidades y limitaciones reales del tratamiento con células madre en las enfermedades neurodegenerativas. La enfermedad de Parkinson con frecuencia se observa desde una perspectiva simplista, como una mera neurodegeneración de la vía dopaminérgica nigroestriada, punto de vista bajo el que se colocan diferentes diseños tendentes a reemplazar la falta de dopamina en el estriado, mediante el empleo de distintos tipos de terapia celular. En este sentido, es necesario señalar por un lado la naturaleza multisistémica y generalizada de la enfermedad, y por otro lado el carácter progresivo del proceso neurodegenerativo de la enfermedad de Parkinson. Bajo este enfoque, pretender que el mero reemplazo de la dopamina estriatal mediante terapia celular sustitutiva, pueda corregir el carácter generalizado y progresivo de la enfermedad es una aspiración quimérica, que únicamente contribuye a generar expectativas infundadas en el público general. Este artículo pretende argumentar desde un punto de vista puramente científico las dudas sobre las expectativas creadas con estos nuevos diseños terapéuticos.At present there is great enthusiasm over the perspectives deriving from so-called cell therapy in Parkinson’s disease. This enthusiasm has spread beyond the ambit of the medical community, reaching the general public, and has been fuelled by a considerable ethical and political debate, sidestepping the need for a really scientific analysis of the real qualities and limitations of treatment with stem-cells in neurodegenerative diseases. Parkinson’s disease is frequently observed from a simplistic perspective, as a mere neurodegeneration of the nigrostriatal dopaminergic pathway. This viewpoint encompasses different designs that tend to replace the lack of dopamine in the striatum through the use of different types of cell therapy. In this respect, it is important to indicate, on the one hand, the multisystemic and generalised nature of the disease and, on the other, the progressive character of the neurodegenerative process of Parkinson’s disease. With this approach, to claim that the mere replacement of striatal dopamine through replacement cell therapy can correct the generalised and progressive character of the disease is a fanciful aspiration, which can only contribute to generating unfounded expectations in the general public. This article attempts to set out from a purely scientific point of view the doubts over the expectations created by these new therapeutic designs

Comparative study of CuO supported on CeO2, Ce0.8Zr0.2O2 and Ce0.8Al0.2O2 based catalysts in the CO-PROX reaction

CuO supported on CeO2, Ce0.8Zr0.2O2 and Ce0.8Al0.2O2 based catalysts (6%wt Cu) were synthesized and tested in the preferential oxidation of CO in a H2-rich stream (CO-PROX). Nanocrystalline supports, CeO2 and solid solutions of modified CeO2 with zirconium and aluminum were prepared by a freeze-drying method. CuO was supported by incipient wetness impregnation and calcination at 400 C. All catalysts exhibit high activity in the CO-PROX reaction and selectivity to CO2 at low reaction temperature, being the catalyst supported on CeO2 the more active and stable. The influence of the presence of CO2 and H2O was also studied

The Landau Pole and Z′Z^{\prime} decays in the 331 bilepton model

We calculate the decay widths and branching ratios of the extra neutral boson $Z^{\prime}$ predicted by the 331 bilepton model in the framework of two different particle contents. These calculations are performed taken into account oblique radiative corrections, and Flavor Changing Neutral Currents (FCNC) under the ansatz of Matsuda as a texture for the quark mass matrices. Contributions of the order of $10^{-1}-10^{-2}$ are obtained in the branching ratios, and partial widths about one order of magnitude bigger in relation with other non- and bilepton models are also obtained. A Landau-like pole arise at 3.5 TeV considering the full particle content of the minimal model (MM), where the exotic sector is considered as a degenerated spectrum at 3 TeV scale. The Landau pole problem can be avoid at the TeV scales if a new leptonic content running below the threshold at $$ TeV is implemented as suggested by other authors.Comment: 20 pages, 5 figures, LaTeX2

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action

BRIVA-LIFE–A multicenter retrospective study of the long-term use of brivaracetam in clinical practice

Objectives: Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy. Materials and Methods: This was a multicenter retrospective study. Patients aged =16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes. Results: A total of 575 patients were included in analyses; most had been treated with =4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were =50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged =65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity. Conclusions: In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure

Surgical treatment for colorectal cancer: Analysis of the influence of an enhanced recovery programme on long-term oncological outcomes-a study protocol for a prospective, multicentre, observational cohort study

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings. Trial registration number NCT04305314

Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory

Atmospheric parameters, such as pressure (P), temperature (T) and density, affect the development of extensive air showers initiated by energetic cosmic rays. We have studied the impact of atmospheric variations on extensive air showers by means of the surface detector of the Pierre Auger Observatory. The rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find that the observed behaviour is explained by a model including the effects associated with the variations of pressure and density. The former affects the longitudinal development of air showers while the latter influences the Moliere radius and hence the lateral distribution of the shower particles. The model is validated with full simulations of extensive air showers using atmospheric profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle Physic