Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain

Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-α and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-κB)p65 levels were not different between the groups. Interleukin-1beta (IL-1β) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder

Prevalencia en nuestro medio de las deformidades dinámicas posicionales del hallux como secuela de las fracturas de tercio medio y distal de tibia

Dynamic positional deformity of the hallux is a relatively new disease, precisely because of its innovative nature and dynamics may go unnoticed to clinicians. It is because of this, that the limited literature available stresses the importance of making an active search for this pathology in our daily practice. The purpose of this study is to estimate the prevalence of these deformities at the University Hospital Dr. Peset of Valencia as well as make an analysis of their management. An analytical, descriptive and retrospective study was designed in which patients admitted in our center during 2014 and 2015 with medium and distal third tibia fracture were analyzed searching for dynamics positional deformities of the hallux. We found a total of 5 compatible cases from 42 analyzed tibia fractures. This may indicate that as expected dynamic positional deformity of the hallux could be an underrated disease in our medium

Cardiovascular preventive recommendations. PAPPS 2020 update

The recommendations of the semFYC's Program for Preventive Activities and Health Promotion (PAPPS) for the prevention of cardiovascular diseases (CVD) are presented. The following sections are included: Epidemiological review, where the current morbidity and mortality of CVD in Spain and its evolution as well as the main risk factors are described; Cardiovascular (CV) risk tables and recommendations for the calculation of CV risk; Main risk factors such as arterial hypertension, dyslipidemia and diabetes mellitus, describing the method for their diagnosis, therapeutic objectives and recommendations for lifestyle measures and pharmacological treatment; Indications for antiplatelet therapy, and recommendations for screening of atrial fibrillation. The quality of testing and the strength of the recommendation are included in the main recommendations.Se presentan las recomendaciones del Programa de Actividades Preventivas y Promoción de la Salud (PAPPS) de la semFYC, para la prevención de las enfermedades cardiovasculares (CV). Se incluyen los siguientes apartados: Revisión epidemiológica, donde se describe la morbimortalidadCV actual en España y su evolución y los principales factores de riesgo; Tablas de riesgo CV y recomendaciones para el cálculo del riesgo CV; Factores de riesgo mayores como hipertensión arterial, dislipidemia y diabetes mellitus, describiendo el método para su diagnóstico, los objetivos terapéuticos y las recomendaciones de medidas d estilo de vida y de tratamiento farmacológico; Indicaciones de antiagregación, y Recomendaciones para el cribado de la fibrilación auricular. Para las principales recomendaciones se incluyen tablas específicas que recogen la calidad de la evidencia y la fuerza de la recomendación

NEXT-100 Technical Design Report (TDR). Executive Summary

In this Technical Design Report (TDR) we describe the NEXT-100 detector that will search for neutrinoless double beta decay (bbonu) in Xe-136 at the Laboratorio Subterraneo de Canfranc (LSC), in Spain. The document formalizes the design presented in our Conceptual Design Report (CDR): an electroluminescence time projection chamber, with separate readout planes for calorimetry and tracking, located, respectively, behind cathode and anode. The detector is designed to hold a maximum of about 150 kg of xenon at 15 bar, or 100 kg at 10 bar. This option builds in the capability to increase the total isotope mass by 50% while keeping the operating pressure at a manageable level. The readout plane performing the energy measurement is composed of Hamamatsu R11410-10 photomultipliers, specially designed for operation in low-background, xenon-based detectors. Each individual PMT will be isolated from the gas by an individual, pressure resistant enclosure and will be coupled to the sensitive volume through a sapphire window. The tracking plane consists in an array of Hamamatsu S10362-11-050P MPPCs used as tracking pixels. They will be arranged in square boards holding 64 sensors (8 times8) with a 1-cm pitch. The inner walls of the TPC, the sapphire windows and the boards holding the MPPCs will be coated with tetraphenyl butadiene (TPB), a wavelength shifter, to improve the light collection.Comment: 32 pages, 22 figures, 5 table

Epidemiology and cost of herpes zoster and postherpetic neuralgia among patients treated in primary care centres in the valencian community of Spain

<p>Abstract</p> <p>Background</p> <p>Data on the epidemiology and costs related to herpes zoster (HZ) and postherpetic neuralgia (PHN) in Spain are scarce; therefore, studies are needed to evaluate the epidemiological and economic impact of HZ and its most common complication, PHN. The present study aimed to estimate the clinical and economic burden of HZ and PHN in Valencia (Spain).</p> <p>Methods</p> <p>We prospectively analyzed the burden of HZ and PHN and their attributable costs in patients from 25 general practices in the Autonomous Community of Valencia serving 36,030 persons aged > 14 years. All patients with a clinical diagnosis of HZ who attended these centers between December 1^st2006 and November 30^th2007 were asked to participate. Patients included were followed for 1 year.</p> <p>Results</p> <p>Of the 130 cases of HZ followed up, continued pain was experienced by 47.6% (95% confidence interval (CI) = 35.6-56.7%) at 1 month after rash onset, by 14.5% (95% CI = 7.8-1.2%) at 3 months, by 9.0% (95% CI = 3.7-14.3%) at 6 months, and by 5.9% (95% CI = 1.5-10.3%) at 12 months. The percentage of patients with PHN increased with age, from 21.4% (95% CI = 8.3-40) in patients < 50 years to 59.2% (95% CI = 44.4-74) in patients ≥ 70 years. The estimated total cost for the 130 HZ cases during the follow-up period was €49,160 ($67,349). Mean cost per patient was €378 (range 53-2,830) ($517, range 73-3,877).</p> <p>Conclusions</p> <p>This study shows that PHN is a relatively common complication of HZ and that both conditions combined give rise to a significant clinical and economic burden for patients and providers.</p

Design and characterization of the SiPM tracking system of NEXT-DEMO, a demonstrator prototype of the NEXT-100 experiment

NEXT-100 experiment aims at searching the neutrinoless double-beta decay of the Xe-136 isotope using a TPC filled with a 100 kg of high-pressure gaseous xenon, with 90% isotopic enrichment. The experiment will take place at the Laboratorio Subterraneo de Canfranc (LSC), Spain. NEXT-100 uses electroluminescence (EL) technology for energy measurement with a resolution better than 1% FWHM. The gaseous xenon in the TPC additionally allows the tracks of the two beta particles to be recorded, which are expected to have a length of up to 30 cm at 10 bar pressure. The ability to record the topological signature of the beta beta 0 nu events provides a powerful background rejection factor for the beta beta experiment. In this paper, we present a novel 3D imaging concept using SiPMs coated with tetraphenyl butadiene (TPB) for the EL read out and its first implementation in NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment. The design and the first characterization measurements of the NEXT-DEMO SiPM tracking system are presented. The SiPM response uniformity over the tracking plane drawn from its gain map is shown to be better than 4%. An automated active control system for the stabilization of the SiPMs gain was developed, based on the voltage supply compensation of the gain drifts. The gain is shown to be stabilized within 0.2% relative variation around its nominal value, provided by Hamamatsu, in a temperature range of 10 degrees C. The noise level from the electronics and the SiPM dark noise is shown to lay typically below the level of 10 photoelectrons (pe) in the ADC. Hence, a detection threshold at 10 pe is set for the acquisition of the tracking signals. The ADC full dynamic range (4096 channels) is shown to be adequate for signal levels of up to 200 pe/mu s, which enables recording most of the tracking signals

Present Status and Future Perspectives of the NEXT Experiment

NEXT is an experiment dedicated to neutrinoless double beta decay searches in xenon. The detector is a TPC, holding 100 kg of high-pressure xenon enriched in the 136Xe isotope. It is under construction in the Laboratorio Subterráneo de Canfranc in Spain, and it will begin operations in 2015. The NEXT detector concept provides an energy resolutionbetter than 1% FWHM and a topological signal that can be used to reduce the background. Furthermore, the NEXT technology can be extrapolated to a 1 ton-scale experiment

Operation and first results of the NEXT-DEMO prototype using a silicon photomultiplier tracking array

NEXT-DEMO is a high-pressure xenon gas TPC which acts as a technological test-bed and demonstrator for the NEXT-100 neutrinoless double beta decay experiment. In its current configuration the apparatus fully implements the NEXT-100 design concept. This is an asymmetric TPC, with an energy plane made of photomultipliers and a tracking plane made of silicon photomultipliers (SiPM) coated with TPB. The detector in this new configuration has been used to reconstruct the characteristic signature of electrons in dense gas, demonstrating the ability to identify the MIP and ''blob'' regions. Moreover, the SiPM tracking plane allows for the definition of a large fiducial region in which an excellent energy resolution of 1.82% FWHM at 511 keV has been measured (a value which extrapolates to 0.83% at the xenon Qββ)

Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment

NEXT-DEMO is a large scale prototype and demonstrator of the NEXT-100 High Pressure Xenon Gas TPC, which will search for the neutrinoless double beta decay of Xe-136 using 100-150 kg of enriched xenon gas. The apparatus was built to prove the expected performance of NEXT-100, namely, energy resolution better than 1% FWHM at 2.5 MeV and event topological reconstruction. In this paper we describe the operation and initial results of the detector. A resolution of 1.7% FWHM at 511 keV (0.77% FWHM at 2.5 MeV) is obtained in the full fiducial volume of the detector. A topological analysis shows that electrons are identified by the characteristic blob energy deposit associated to the Bragg peak in 98.5% of the cases, with a rate of misidentification (two blobs) of 0.14%