Mejora de la productividad, seguridad y salud en células de desmontaje en una empresa de remanufactura de transmisiones de vehículos

El objeto de este Trabajo Fin de Grado es mejorar la productividad de un proceso productivo de la empresa GKN Ayra Servicio, concretamente el desmontaje de cascos de transmisión de vehículos. Además, este trabajo tiene también como objetivo la mejora de la ergonomía, seguridad y salud de los empleados de esta área de la fábrica. El alcance de este proyecto se limita a implantar mejoras en el proceso productivo citado.Graduado o Graduada en Ingeniería Mecánica por la Universidad Pública de NavarraIngeniaritza Mekanikoko Graduatua Nafarroako Unibertsitate Publikoa

Paliperidone Reversion of Maternal Immune Activation-Induced Changes on Brain Serotonin and Kynurenine Pathways

Emerging evidence indicates that early-life exposure to environmental factors may increase the risk for schizophrenia via inflammatory mechanisms. Inflammation can alter the metabolism of tryptophan through the oxidative kynurenine pathway to compounds with neurotoxic and neuroprotective activity and compromise serotonin (5-HT) synthesis. Here we investigate the role of serotonergic and kynurenine pathways in the maternal immune activation (MIA) animal model of schizophrenia. The potential reversion exerted by long-term antipsychotic treatment was also evaluated. MIA was induced by prenatal administration of polyinosinic:polycytidylic acid (poly (I:C)) in mice. Expression of different proteins and the content of different metabolites involved in the function of serotonergic and kynurenine pathways was assessed by RT-PCR, immunoblot and ELISA analyses in frontal cortex of the offspring after puberty. MIA decreased tissue 5-HT content and promoted changes in the expression of serotonin transporter, 5-HT2A and 5-HT2C receptors. Expression of indoleamine 2,3-dioxygenase 2 (IDO2) and kynurenine 3-monooxygenase (KMO) was increased by poly (I:C) whereas kynurenine aminotransferase II and its metabolite kynurenic acid were not altered. Long-term paliperidone was able to counteract MIA-induced changes in 5-HT and KMO, and to increase tryptophan availability and tryptophan hydroxylase-2 expression in poly (I:C) mice but not in controls. MIA-induced increase of the cytotoxic risk ratio of kynurenine metabolites (quinolinic/kynurenic acid) was also reversed by paliperidone. MIA induces specific long-term brain effects on serotonergic activity. Such effects seem to be related with alternative activation of the kynurenine metabolic pathway towards a cytotoxic status. Atypical antipsychotic paliperodine partially remediates abnormalities observed after MIA.This work was supported by MINECO-FEDER Funds (SAF201675500-R to JL; SAF2017-88126-R to JM); Centro de Investigacion en Red de Salud Mental, CIBERSAM; and the Basque Government (IT1211-19). Editoria

Characterization of dopamine D2 receptor coupling to G proteins in postmortem brain of subjects with schizophrenia

Background: Alterations of dopamine D-1 (D1R) and D-2 receptor (D2R) are proposed in schizophrenia but brain neuroimaging and postmortem studies have shown controversial results in relation to D1R and D2R density. Besides, scarce information on the functionality of brain D1R and D2R is available. The present study characterized G-protein activation by D1R and D2R agonists in postmortem human brain. Furthermore, D2R functional status was compared between schizophrenia and control subjects. Methods: G-protein receptor coupling was assessed in control caudate nucleus and frontal cortex by [S-35]GTP gamma S-binding stimulation induced by increasing concentrations (10(-10)-10(-3) M) of dopamine, and the selective dopaminergic agonists SKF38393 (D1R) and NPA (D2R). Concentration-response curves to NPA stimulation of [S-35]GTP gamma S binding were analyzed in antipsychotic-free (n = 10) and antipsychotic-treated (n = 7) schizophrenia subjects and matched controls (n = 17). Results: In caudate, [S-35]GTP gamma S-binding responses to agonists were compatible with the existence of functional D2R. In contrast, stimulations in cortex showed responses that did not correspond to D1R or D2R. [S-35]GTP gamma S-binding activation by NPA in caudate displayed biphasic curves with similar profile in schizophrenia (EC50H = 7.94 nM; EC50L = 7.08 mu M) and control (EC50H = 7.24 nM; EC50L = 15.14 mu M) subjects. The presence or absence of antipsychotic medication did not influence the pharmacological parameters. Conclusions: Feasibility of functional evaluation of dopamine receptors in postmortem human brain by conventional [S-35]GTP gamma S-binding assays appears to be restricted to signalling through inhibitory G(i/o) proteins. These findings provide functional information about brain D2R status in subjects with schizophrenia and do not support the existence of D2R supersensitive in this mental disorder.This work was supported by the Spanish State Research Agency and EDR Funds (SAF-2017-88126-R to JJM;PID2019-106404RB-100 to LFC), the Basque Government (IT1211/19 to JJM ; ELKARTEK Programme KK-2019/00049 to RD-A), and the National Institutes of Health (R01MH084894 & NIH-R01MH111940 to JG-M)

¿Llegan oportunamente los pacientes con nefropatía diabética al servicio de Nefrología del Hospital Nacional Cayetano Heredia durante el periodo enero 2011- enero 2012?

La nefropatía diabética está reportada, a nivel local, como la primera causa de enfermedad renal crónica terminal; no se puede efectuar prevención secundaria en estos pacientes por la llegada inoportuna a la primera consulta nefrológica. Objetivos: Determinar la proporción de pacientes con nefropatía diabética que llegan en forma oportuna a la primera consulta nefrológica en el Hospital Cayetano Heredia. Material y Método: Se obtuvieron datos demográficos, clínicos y de laboratorio de 73 pacientes con diagnóstico de Diabetes mellitus 2 durante el periodo de enero de 2011 - enero 2012. Se describen tasas y proporciones. Resultados: De 73 pacientes evaluados, 50 (68,49%) llegaron en forma inoportuna (nefropatía diabética estadio IV y V de Mogensen), siendo predominante el estadio IV en 47(64,38%) y estadio V en 3 (4,11%). Sólo 7 (9,59 %) llegaron en estadio II y ningún paciente llegó en estadio I. 12 (92,31%) fueron transferidos de la Emergencia. Los niveles de depuración de creatinina tuvieron una media en 59,24 ± 43 2 cc/min x 1,73 m sc (1,86-293). Los valores de la proteinuria fueron 2,353 ± 3,291 gr/24 horas, con un rango (29 - 15103 gr) de los cuales 43 (61,43%) presentaron proteinuria significativa, 14 (20%) proteinuria masiva y 3 (4,29%) en rango maligno. Conclusiones: En esta serie la mayor proporción de pacientes con nefropatía diabética llegan en forma inoportuna o en estadios avanzados de enfermedad renal crónica a la consulta externa nefrológica

Behavioural Evaluation of a Translational Animal Model of Schizophrenia

Presented at 1st Meeting in Translational Pharmacology 38th SEF national meeting/9th SEFF meeting 19–20 June 2018, SpainSchizophrenia (SZ) is a chronic and disabling psychiatric disorder affecting about 1% of the population worldwide. Schizophrenia comprises positive and negative symptoms as well as cognitive deficits. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop SZ along lifetime, which in combination with stressful events in adolescence may lead to the SZ onset. The aim of the present study was to create a translational “double-hit” animal model of SZ in male and female mice, based in maternal immune activation (MIA, hit-1)—injection of poly(I:C) to pregnant dams, 7.5 mg/kg i.p.—and social isolation (SI, hit-2) in the peri-pubertal period (3–11 weeks). In the four experimental groups (hit-1, hit-2, double-hit and control) locomotion and anxiety were assessed using the Open Field Test (OFT), and the cognitive status (declarative/episodic memory) was evaluated by means of the Novel Object Recognition Test (NORT). No differences were observed in the spontaneous locomotor activity between any of the groups, neither in females nor in males. However, an increase in the percentage of time spent in the centre of the OFT was significantly associated to the hit-1 (MIA) only in female mice (F[1,53] = 4.252; P = 0.044, n = 57). Moreover, a significant decrease in the discrimination index in the NORT was also associated to the hit-1 (MIA) in the subgroup of female mice (F[1,55] = 7.266; P = 0.0093, n = 59). These preliminary results indicate that MIA produces a greater impact in female mice inducing an anxiolytic-like phenotype and cognitive impairments.Basque Government (IT616/13) MSCA-2016-IF 747487 to C.Muguruza

Economics of gastroenteropancreatic neuroendocrine tumors : a systematic review

Despite current interest, enthusiasm and progress in the development of therapies for gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), there are substantial gaps in the published literature regarding cost-of-illness analyses, economic evaluation and budget impact analyses. Compounding the issue is that data on resource utilization and cost-effectiveness of different diagnostic and therapeutic modalities for GEP-NETs are scarce. A systematic review on the economic impact of GEP-NETs was carried out using four databases: EMBASE, PubMed, the National Health Service Economic Evaluation Database and Cochrane review. Fully published articles from January 2000 to May 2017, in English and Spanish, were included. All articles that satisfied the inclusion criteria were included in the systematic review; summary descriptive statistics were used to describe the methodological characteristics. The 14 studies selected included cost-of-illness analyses (n = 4), economic evaluations (n = 7) and budget impact analyses (n = 3). Almost all studies were performed in the United States. Healthcare costs for patients with NETs included medication, outpatient visits, hospitalizations, and check-ups/tests. Reducing adverse events is an area where cost savings could be achieved; however, there was not enough evidence on the cost impact of adverse events. There is a lack of data related to resource utilization in the field of GEP-NETs. Therefore, cost-effectiveness and budget impact studies of existing and emerging treatments are urgently needed to help the decision-making process for patients with NETs

Inhibition of Prolyl Oligopeptidase Restores Prohibitin 2 Levels in Psychosis Models: Relationship to Cognitive Deficits in Schizophrenia

Cognitive impairment represents one of the core features of schizophrenia. Prolyl Oligopeptidase (POP) inhibition is an emerging strategy for compensating cognitive deficits in hypoglutamatergic states such as schizophrenia, although little is known about how POP inhibitors exert their pharmacological activity. The mitochondrial and nuclear protein Prohibitin 2 (PHB2) could be dysregulated in schizophrenia. However, altered PHB2 levels in schizophrenia linked to N-methyl-D-aspartate receptor (NMDAR) activity and cognitive deficits are still unknown. To shed light on this, we measured the PHB2 levels by immunoblot in a postmortem dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects, in the frontal pole of mice treated with the NMDAR antagonists phencyclidine and dizocilpine, and in rat cortical astrocytes and neurons treated with dizocilpine. Mice and cells were treated in combination with the POP inhibitor IPR19. The PHB2 levels were also analyzed by immunocytochemistry in rat neurons. The PHB2 levels increased in DLPFC in cases of chronic schizophrenia and were associated with cognitive impairments. NMDAR antagonists increased PHB2 levels in the frontal pole of mice and in rat astrocytes and neurons. High levels of PHB2 were found in the nucleus and cytoplasm of neurons upon NMDAR inhibition. IPR19 restored PHB2 levels in the acute NMDAR inhibition. These results show that IPR19 restores the upregulation of PHB2 in an acute NMDAR hypoactivity stage suggesting that the modulation of PHB2 could compensate NMDAR-dependent cognitive impairments in schizophrenia.This research was funded by a Miguel Servet grant, MS16/00153-CP16/00153 to BR, financed and integrated into the National R+D+I and funded by the Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health)—General Branch Evaluation and Promotion of Health Research—and the European Regional Development Fund (ERDF). This work was also supported by ISCIII PI18/00213 to BR, the Predoctoral Fellowship Program from the ISCIII (PFIS) FI19/00080 to E.V, FPU fellowship from the Spanish Ministry of Education, Culture, and Sports FPU17/06000 to E.E., the CONICYT-Doctorado Becas Chile 2015, 72160426 to AV, and the CIBERSAM (Spanish Ministry of Economy, Industry, and Competitiveness, Institute of Health Carlos III). CIBERSAM will be encharged to fund open access publication fees

The health and economic burden of smoking in 12 Latin American countries and the potential effect of increasing tobacco taxes: an economic modelling study

Background: Worldwide, smoking tobacco causes 7 million deaths annually, and this toll is expected to increase, especially in low-income and middle-income countries. In Latin America, smoking is a leading risk factor for death and disability, contributes to poverty, and imposes an economic burden on health systems. Despite being one of the most effective measures to reduce smoking, tobacco taxation is underused and cigarettes are more affordable in Latin America than in other regions. Our aim was to estimate the tobacco-attributable burden on mortality, disease incidence, quality of life lost, and medical costs in 12 Latin American countries, and the expected health and economic effects of increasing tobacco taxes. Methods: In this modelling study, we developed a Markov probabilistic microsimulation economic model of the natural history, medical costs, and quality-of-life losses associated with the most common tobacco-related diseases in 12 countries in Latin America. Data inputs were obtained through a literature review, vital statistics, and hospital databases from each country: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Mexico, Paraguay, Peru, and Uruguay. The main outcomes of the model are life-years, quality-adjusted life-years, disease events, hospitalisations, disease incidence, disease cost, and healthy years of life lost. We estimated direct medical costs for each tobacco-related disease included in the model using a common costing methodology for each country. The disease burden was estimated as the difference in disease events, deaths, and associated costs between the results predicted by the model for current smoking prevalence and a hypothetical cohort of people in each country who had never smoked. The model estimates the health and financial effects of a price increase of cigarettes through taxes, in terms of disease and health-care costs averted, and increased tax revenues. Findings: In the 12 Latin American countries analysed, we estimated that smoking is responsible for approximately 345 000 (12%) of the total 2 860 921 adult deaths, 2·21 million disease events, 8·77 million healthy years of life lost, and $26·9 billion in direct medical costs annually. Health-care costs attributable to smoking were estimated to represent 6·9$26·7 billion in health-care costs in the next 10 years, with a total economic benefit of $43·7 billion. Interpretation: Smoking represents a substantial health and economic burden in these 12 countries of Latin America. Tobacco tax increases could successfully avert deaths and disability, reduce health-care spending, and increase tax revenues, resulting in large net economic benefits.Fil: Pichón-riviere, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Alcaraz, Andrea. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Palacios, Alfredo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Rodríguez, Belén. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Reynales Shigematsu, Luz Myriam. Instituto Nacional de Salud Pública; MéxicoFil: Pinto, Márcia. Fundación Oswaldo Cruz; BrasilFil: Castillo Riquelme, Marianela. Ministerio de Salud; ChileFil: Peña Torres, Esperanza. Instituto de Evaluación Tecnológica En Salud; ColombiaFil: Osorio, Diana Isabel. Instituto de Evaluación Tecnológica en Salud; ColombiaFil: Huayanay, Leandro. Universidad Peruana Cayetano Heredia; PerúFil: Loza Munarriz, Cesar. Universidad Peruana Cayetano Heredia; PerúFil: Sáenz de Miera-Juárez, Belén. Universidad Autónoma de Baja California Sur; MéxicoFil: Gallegos Rivero, Verónica. Centro Nacional de Excelencia Tecnológica en Salud; MéxicoFil: De La Puente, Catherine. Universidad de La Frontera; ChileFil: Navia Bueno, María del Pilar. Universidad Mayor de San Andrés; BoliviaFil: Caporale, Joaquín. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Roberti, Javier Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Virgilio, Sacha Alexis. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin