Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

first_page settings Open AccessArticle Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age by Diego Delgado 1, Ane Miren Bilbao 2, Maider Beitia 1, Ane Garate 1, Pello Sánchez 1, Imanol González-Burguera 3,4, Amaia Isasti 4,5, Maider López De Jesús 4,5,6, Jone Zuazo-Ibarra 7, Alejandro Montilla 7 [OrcID] , María Domercq 7 [OrcID] , Estibaliz Capetillo-Zarate 7,8, Gontzal García del Caño 3,4 [OrcID] , Joan Sallés 4,5,6, Carlos Matute 7 and Mikel Sánchez 1,2,* 1 Advanced Biological Therapy Unit, Hospital Vithas Vitoria, 01008 Vitoria-Gasteiz, Spain 2 Arthroscopic Surgery Unit, Hospital Vithas Vitoria, 01008 Vitoria-Gasteiz, Spain 3 Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01008 Vitoria-Gasteiz, Spain 4 Bioaraba, Neurofarmacología Celular y Molecular, 01008 Vitoria-Gasteiz, Spain 5 Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01008 Vitoria-Gasteiz, Spain 6 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain 7 Achucarro Basque Center for Neuroscience, CIBERNED and Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU), 48940 Leioa, Spain 8 IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain * Author to whom correspondence should be addressed. Academic Editor: Francesca Santilli Int. J. Mol. Sci. 2021, 22(4), 1725; https://doi.org/10.3390/ijms22041725 Received: 24 November 2020 / Revised: 12 January 2021 / Accepted: 3 February 2021 / Published: 9 February 2021 (This article belongs to the Section Molecular Endocrinology and Metabolism) Download PDF Browse Figures Citation Export Abstract Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.This work was funded by the Provincial Council of Alava through the AlavaInnova Program, Basque Government through the GAITEK Program, Ministry of Economy, Industry and Competitiveness (CTQ2017-85686-R), Spanish Ministry of Education and Science (PID2019-109724RB-I00), Basque Government (IT1203-19, IT1230-19, and KK-2020/00034) and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Dry selection and wet evaluation for the rational discovery of new anthelmintics

Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a TOMOCOMD-CARDD (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmintics. The model shows an accuracy of 86.84% in the training set and 94.44% in the external prediction set. Finally, we carry out an experiment to predict the biological profile of our ‘in-house’ collections of indole, indazole, quinoxaline and cinnoline derivatives (∼200 compounds). Subsequently, we selected a group of nine of the theoretically most active structures. Then, these chemicals were tested in an invitro assay and one good candidate (VA5-5c) as fasciolicide compound (100% of reduction at concentrations of 50 and 10 mg/L) was discovered.Yovani Marrero-Ponce acknowledges the support from USFQ with partial finance of project ID5455Peer Reviewe

Integrando escalas y métodos LTER para comprender la dinámica global de un espacio protegido de montaña: el Parque Nacional de Ordesa y Monte Perdido

Los espacios protegidos, por el hecho de albergar una gran geo-biodiversidad y asegurar una baja intervención humana, constituyen lugares muy adecuados para el seguimiento de organismos y procesos a escala ecológica, así como para la obtención de series temporales largas a escala geológica. En el marco de la red LTER-España, el Parque Nacional de Ordesa y Monte Perdido (PNOMP) y el Instituto Pirenaico de Ecología-CSIC están impulsando estudios para la detección de cambios a distintas escalas mediante variados métodos y aproximaciones. Destacamos aquí los más consolidados, entre los que se encuentran los análisis de registros de sedimentos en lagos, espeleotemas en cuevas, la dinámica de uno de los pocos glaciares activos de la Península ibérica, el análisis físico-químico de aguas corrientes e ibones de alta montaña, el registro del cambio climático actual en árboles longevos, la afección que éste ejerce sobre masas actuales de pinos en el límite superior del bosque y de abetales en zonas húmedas, la matorralización de algunos pastos y los procesos mecanicistas que subyacen, la reorganización de la diversidad florística en pastos tras el abandono paulatino o drástico de la ganadería, la biodiversidad de las comunidades alpinas y la dinámica poblacional de especies amenazadas o indicadoras de hábitats o de motores de cambio global. Los seguimientos ecológicos actuales muestran que tanto el cambio climático como el de usos del suelo están teniendo una considerable trascendencia en la fisionomía y la estructura de algunos de los ambientes más icónicos y frecuentes del parque (deterioro del glaciar, termofilización de la flora en cumbres alpinas, densificación del bosque en su límite superior, pérdida de productividad en algunos pastos supraforestales, etc.). También sugieren una importante variabilidad espacial en los procesos (por ej. en el PNOMP conviven pastos matorralizados y pastos muy estables), y evidencian que los cambios observados no siempre siguen los paradigmas establecidos (por ej., las especies amenazadas mantienen dinámicas poblacionales estables). La integración de resultados parciales proporcionados por cada aproximación relativiza la importancia de las percepciones que cada estudio destaca por separado, y permite medir los cambios actuales en el marco de referencia de los cambios a escala geológica. Predecir la resistencia y resiliencia de los ecosistemas o las poblaciones de seres vivos para enfrentarse a los futuros cambios ambientales es complicado, no sólo por la falta de conocimientos disponibles sino también porque las respuestas que observamos no siempre son tan rápidas o lineales como se espera. La modelización constituye una herramienta cada vez más utilizada, pero requiere de evidencias reales para validar sus pronósticos, por lo que la observación de los procesos que actúan en el PNOMP ha de incluir un esfuerzo continuado de monitorización multiescalar y multidisciplinar de los distintos componentes de la geo, hidro-, crio- y biosfera, sin olvidar el componente humano. Entender la complejidad supone conectar las interacciones que existen entre todos los sistemas y ponderar sus efectos según las escalas de trabajo.Instituto Pirenaico de Ecología, Consejo Superior de Investigaciones Científicas, EspañaEmpresa pública SARGA, EspañaJOLUBE Consultor Botánico, Editor y Fotógrafo, EspañaDepartament d’Ecologia, Universitat de Barcelona, EspañaUnidad de Tres Cantos, Instituto Geológico y Minero de España, EspañaInstitut de Recerca de Biodiversitat, Universitat de Barcelona, EspañaParque Nacional de Ordesa y Monte Perdido, Españ

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir &lt;100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles.DiscussionWhereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available

Mis casos clínicos de especialidades odontológicas

Libro que muestra la atención de casos clínicos particulares referente a las diferentes especialidades odontológicasLibro que muestra la atención de casos clínicos particulares referente a las diferentes especialidades odontológicasUniversidad Autónoma de Campeche Universidad Autónoma del Estado de Hidalgo Universidad Autónoma del Estado de Méxic

Ciencia Odontológica 2.0

Libro que muestra avances de la Investigación Odontológica en MéxicoEs para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el segundo de una serie de 6 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la UAEH, UAEM, UAC y UdeG