The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age

Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focus on the maternal genetic makeup of the Neolithic (~ 5500–3000 BCE), Chalcolithic (~ 3000–2200 BCE) and Early Bronze Age (~ 2200–1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character.Concerning research in the Alto Ribatejo, authors wish to thank Fundação para a Ciência e Tecnologia the support of research on the dawn of farming in the Tagus valley (project “Moving Tasks Accross Shapes” – PTDC/EPH-ARQ/4356/2014), as well as the Geosciences Centre of Coimbra University (strategic project UID/Multi/00073/2013). This study was funded by the German Research Foundation (Grant no. Al 287/14–1)

Pricing and reimbursement mechanisms for advanced therapy medicinal products in 20 countries

Introduction: Advanced Therapy Medicinal Products are a type of therapies that, in some cases, hold great potential for patients without an effective current therapeutic approach but they also present multiple challenges to payers. While there are many theoretical papers on pricing and reimbursement (P&R) options, original empirical research is very scarce. This paper aims to provide a comprehensive international review of regulatory and P&R decisions taken for all ATMPs with centralized European marketing authorization in March 2022. Methods: A survey was distributed in July 2022 to representatives of 46 countries. Results: Responses were received from 20 countries out of 46 (43.5%). 14 countries reimbursed at least one ATMP. Six countries in this survey reimbursed no ATMPs. Conclusion: Access to ATMPs is uneven across the countries included in this study. This arises from regulatory differences, commercial decisions by marketing authorization holders, and the divergent assessment processes and criteria applied by payers. Moving towards greater equality of access will require cooperation between countries and stakeholders, for example, through the WHO Regional Office for Europe’s Access to Novel Medicines Platform.Project PID 2019.105597RA.I00 financed by the Spanish Ministry of Science and Innovation/National Research Agency MCIN/AEI/10.13039/ 50110001103

Un año de pacientes nuevos en un Servicio de Salud Mental.

Muestra con 1.406 pacientes nuevos en el Servicio de Salud Mental de Aranjuez (2004), para realizar un perfil sociodemográfico de los pacientes nuevos vistos durante ese año, y conocer la distribución de las categorías diagnósticas totales y en función de las variables sexo y edad

Implementación de un ambiente WEB para la publicación de productos industriales y cobros mediante tarjeta de crédito o por medio de un link de pagos

Este documento tiene como finalidad hacer una mejora a los procesos que se llevan a cabo en la empresa que en sus inicios eran óptimos debido al tamaño de la empresa y su única línea de negocios. Sin embargo, conforme el tiempo avanza, la empresa ha atraído a más clientes lo que conlleva un mayor número de transacciones y con esto un flujo de información mucho mayor al inicial, a tal punto que ya no es posible llevar todos los procesos de forma manual, además que resulta mucho más complejo manipular tal cantidad de información

Estudio descriptivo de los niños y adolescentes nuevos vistos en un servicio de salud mental en el periodo de un año.

En este trabajo se presenta un estudio descriptivo de los niños y adolescentes nuevos vistos en el Servicio de Salud Mental de Aranjuez (Área 11 de la Comunidad de Madrid) durante el año 2004. La muestra clínica consta de 314 pacientes nuevos. El propósito del estudio es doble: por un lado presentar algunas características sociodemográficas de los niños y adolescentes nuevos vistos y, por otro, mostrar los diagnósticos y las diferencias en función de la edad y el sexo. Se ha recurrido al programa informático de los Servicios de Salud Mental de distrito de la Comunidad de Madrid (Registro Acumulado de Casos: R. A. C.) para la obtención de los datos

‘Aplicación de los criterios STOPP - START en la determinación de polifarmacia y prescripción inapropiada que afectan la calidad de vida en los adultos mayores de 65 años de edad o más de los Centros de Salud Las Casas y Conocoto, de septiembre a noviembre del 2.016.’

La población adulta mayor incrementa en el transcurso del tiempo, con la coexistencia de múltiples patologías, por ello es fácil incurrir en prescripciones inapropiadas de fármacos lo que puede provocar serias reacciones medicamentosas en los pacientes (1), aumentando el costo del cuidado de la salud y disminución en la calidad de vida de los individuos involucrados.(2) En el presente estudio se aplicó los criterios STOPP-START, a la población adulta mayor con criterios de polifarmacia que asiste a los centros de salud de las Casas y Conocoto; que permitirán valorar la prescripción inapropiada que puedan afectar la calidad de vida de esta población. Se realizó un estudio de corte y asociación de variables con el fin de evaluar las probables diferencias y similitudes en estas dos áreas de salud; para determinar la prescripción inapropiada en los pacientes con polifarmacia mediante el uso de los criterios STOPP-START y a su vez valorar la calidad de vida con el cuestionario de Salud SF-12. Se encontró asociación entre mala calidad de vida del Adulto Mayor con polifarmacia y la prescripción inapropiada; además de una asociación con el número de prescriptores, así en el C.S. Las Casas el RR = 2,07, chi2 = 6,59 con p < 0,05 y C.S. Conocoto el RR = 2,77, chi2 = 5,56 con p < 0,05. Este estudio propone tener una línea de base que permitirá conocer la realidad de este grupo et

Neuroprotective Effects of Bioavailable Polyphenol-Derived Metabolites against Oxidative Stress-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells

Oxidative stress is involved in cell death in neurodegenerative diseases. Dietary polyphenols can exert health benefits, but their direct effects on neuronal cells are debatable because most phenolics are metabolized and do not reach the brain as they occur in the dietary sources. Herein, we evaluate the effects of a panel of bioavailable polyphenols and derived metabolites at physiologically relevant conditions against H2O2-induced apoptosis in human neuroblastoma SH-SY5Y cells. Among the 19 metabolites tested, 3,4-dihydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid, gallic acid, ellagic acid, and urolithins prevented neuronal apoptosis via attenuation of ROS levels, increased REDOX activity, and decreased oxidative stress-induced apoptosis by preventing the caspase-3 activation via the mitochondrial apoptotic pathway in SH-SY5Y cells. This suggests that dietary sources containing the polyphenol precursors of these molecules such as cocoa, berries, walnuts, and tea could be potential functional foods to reduce oxidative stress associated with the onset and progress of neurodegenerative diseases.This work was funded by Projects CICYT AGL2011-22447, AGL2015-64124-R (MINECO, Spain), 201370E068 (CSIC, Spain), and BACCHUS (FP7-KBBE-2012-6-single stage, European Commission Grant Agreement 312090). A.G.-S. and M.A.N.-S. are holders of a “Juan de la Cierva” contract and an FPI grant, respectively, from MINECO.Peer reviewe

A Human Pharmacokinetic Study

Funding: This research was supported by the Projects PID2019-103914RB-I00 and PID2019-109369RBI00 from the Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033, Spain). C.E.I.- A. is the holder of a predoctoral grant FPU18/03961 from MICIN. M.C.L.-H. is a receipt of a Juan de la Cierva Grant IJC2020-044353-I/MCIN/AEI/10.13039/501100011033/EU/PRTR.Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, including the brain, by crossing the blood-brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed here to explore (i) whether resveratrol and (or) its derived metabolites are found in the cargo of human plasma exosome-containing EVs (E-EVs), (ii) when this incorporation occurs, and (iii) whether resveratrol intake stimulates the release of E-EVs. Thus, in a pharmacokinetic study, healthy volunteers (n = 16) consumed 1 capsule (420 mg resveratrol) in the evening before attending the clinic and one more capsule on the day of the pharmacokinetics. The plasma and the isolated E-EVs were analyzed using UPLC-ESI-QTOF-MS. Of 17 metabolites in the plasma, 9 were identified in the E-EVs, but not free resveratrol. The kinetic profiles of resveratrol metabolites were similar in the plasma and the E-EVs, a higher metabolite concentration being detected in the plasma than in the E-EVs. However, the plasma/E-EVs ratio decreased in the gut microbial metabolites, suggesting their better encapsulation efficiency in E-EVs. In addition, glucuronide conjugates of resveratrol, dihydroresveratrol, and lunularin were incorporated into the E-EVs more efficiently than their corresponding sulfates despite glucuronides reaching lower plasma concentrations. Notably, more E-EVs were detected 10 h after resveratrol consumption. This exploratory study provides the first evidence that (i) resveratrol metabolites are transported by E-EVs, with a preference for glucuronide vs. sulfates, (ii) the gut microbial metabolites concentration and kinetic profiles are closely similar in E-EVs and plasma, and (iii) resveratrol intake elicits E-EVs secretion. Overall, these results open new research avenues on the possible role of E-EVs in (poly)phenol health effects.publishersversionpublishe