Impact of chronic risperidone use on behavior and survival of 3xTg-AD mice model of Alzheimer's disease and mice with normal aging

Altres ajuts: FLMTV3/2010/062930Psychosis and/or aggression are common problems in dementia, and when severe or persistent, cause considerable patient distress and disability, caregiver stress, and early institutionalization. In 2005, the Food and Drug Administration (FDA) determined that atypical antipsychotics were associated with a significantly greater mortality risk compared to placebo, which prompted the addition of an FDA black-box warning. The American College of Neuropsychopharmacology (ACNP) White Paper, 2008, reviewed this issue and made clinical and research recommendations regarding the use of antipsychotics in dementia patients with psychosis and/or agitation. Increased mortality risk has also been described in cerebrovascular adverse events in elderly users of antipsychotics. In the present work, at the translational level, we used male 3xTg-AD mice (PS1M146V, APPSwe, tauP301L) at advanced stages of the disease reported to have worse survival than females, to study the behavioral effects of a low chronic dose of risperidone (0.1 mg/ kg, s.c., 90 days, from 13 to 16 months of age) and its impact on long-term survival, as compared to mice with normal aging. Animals were behaviorally assessed for cognitive and BPSD (behavioral and psychological symptoms of dementia)-like symptoms in naturalistic and experimental conditions (open-field test, T-maze, social interaction, Morris water maze, and marble test) before and after treatment. Weight, basal glucose levels, and IPGTT (i.p. glucose tolerance test) were also recorded. Neophobia in the corner test was used for behavioral monitoring. Survival curves were recorded throughout the experiment until natural death. The benefits of risperidone were limited, both at cognitive and BPSD-like level, and mostly restricted to burying, agitation/vibrating tail, and other social behaviors. However, the work warns about a clear early mortality risk window during the treatment and long-lasting impact on survival. Reduced life expectancy and life span were observed in the 3xTg-AD mice, but total lifespan (36 months) recorded in C57BL/6 × 129Sv counterparts with normal aging was also truncated to 28 months in those with treatment. Sarcopenia at time of death was found in all groups, but was more severe in wild-type animals treated with risperidone. Therefore, the 3xTg-AD mice and their non-transgenic counterparts can be useful to delimitate critical time windows and for studying the physio-pathogenic factors and underlying causal events involved in this topic of considerable public health significance

Eficacia de la pliometría en la fatiga neuromuscular en triatlón: estudio piloto

Las transiciones en triatlón afectan al rendimiento y riesgo de lesión. El objetivo fue determinar la fatiga neuromuscular inducida por 40 km de ciclismo y la eficacia del entrenamiento pliométrico en la fatiga y rendimiento de la carrera a pie. Participaron doce triatletas, 5 realizaron un entrenamiento pliométrico y 7 continuaron su entrenamiento habitual. Se realizaron tests de salto antes y después de 40 km de ciclismo para determinar la fatiga y se registró el ritmo de 5 km de carrera. Se observaron diferencias significativas en la altura de salto (p<0,05) indicando que 40 km de ciclismo inducen fatiga en la extremidad inferior. Tras el entrenamiento pliométrico se observaron mejoras significativas en el test Squat Jump posterior al ciclismo (p=0,038) y en el ritmo del primer kilómetro (p=0,015). El entrenamiento pliométrico parece ser más eficaz que el entrenamiento habitual para mejorar la fatiga neuromuscular y el ritmo del primer kilómetro

miR-1226 detection in GCF as potential biomarker of chronic periodontitis: a pilot study

The study and identification of new biomarkers for periodontal disease, such as microRNAs (miRNAs), may give us more information about the location and severity of the disease and will serve as a basis for treatment planning and disease-monitoring. miRNAs are a group of small RNAs which are involved in gene regulation by binding to their messenger RNA target (mRNA). In this pilot study, the procedure for purifying miRNAs from gingival crevicular fluid (GCF) was, for the first time, described. In addition, the concentration of miRNAs in GCF was analyzed and compared between patients with moderate or severe chronic periodontitis (CP) and healthy controls. GCF samples were collected from single-rooted teeth of patients with moderate or severe CP (n=9) and of healthy individuals (n=9). miRNAs were isolated from GCF using miRNeasy Serum/Plasma kit (Qiagen, CA. USA). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression of a series of miRNAs candidates that are related to bone metabolism. The significance of differences in miRNA levels between both groups was determined using Mann-Whitney U test. The results from this pilot study indicate that miRNAs can be isolated from GCF. Six different miRNAs were analyzed (miR-671, miR-122, miR-1306, miR-27a, miR-223, miR-1226), but only miR-1226 showed statically significant differences between the CP group and healthy controls (p<0.05). This miRNA was downregulated in patients with CP. Within the limitations of the present study, it may be concluded that miR-1226 can be a promising biomarker for periodontal disease, adding relevant information to common clinical parameters used for diagnosis and prognosis of periodontitis

Cellular Responses in Human Dental Pulp Stem Cells Treated with Three Endodontic Materials

Human dental pulp stem cells (HDPSCs) are of special relevance in future regenerative dental therapies. Characterizing cytotoxicity and genotoxicity produced by endodontic materials is required to evaluate the potential for regeneration of injured tissues in future strategies combining regenerative and root canal therapies. This study explores the cytotoxicity and genotoxicity mediated by oxidative stress of three endodontic materials that are widely used on HDPSCs: a mineral trioxide aggregate (MTA-Angelus white), an epoxy resin sealant (AH-Plus cement), and an MTA-based cement sealer (MTA-Fillapex). Cell viability and cell death rate were assessed by flow cytometry. Oxidative stress was measured by OxyBlot. Levels of antioxidant enzymes were evaluated by Western blot. Genotoxicity was studied by quantifying the expression levels of DNA damage sensors such as ATM and RAD53 genes and DNA damage repair sensors such as RAD51 and PARP-1. Results indicate that AH-Plus increased apoptosis, oxidative stress, and genotoxicity markers in HDPSCs. MTA-Fillapex was the most cytotoxic oxidative stress inductor and genotoxic material for HDPSCs at longer times in preincubated cell culture medium, and MTA-Angelus was less cytotoxic and genotoxic than AH-Plus and MTA-Fillapex at all times assayed

Reutilización de botellas de plástico en la localidad de Saladas

El proyecto de extensión “Construir reciclando”, financiado por la Secretaría de Políticas Universitarias fue realizado por alumnos del Profesorado en Ciencias Químicas y del Ambiente junto a docentes de la FaCENA - UNNE. El mismo estuvo destinado a crear una actitud comprometida con el medio ambiente. El reciclado es un tema que nos afecta a todos por igual. El medio ambiente, los recursos naturales y el ser humano con todas sus actividades están estrechamente relacionados y si alguno de estos componentes influye de manera positiva o negativa sobre el/los otro/s, todo el sistema va a notar ese cambio. Este trabajo se realizó con alumnos y docentes de la Escuela Técnica Dr. Juan Gregorio Pujol, de la localidad de Saladas de la provincia de Corrientes. Las actividades desarrolladas se orientaron hacia la elaboración de ladrillos ecológicos como así también a la confección de “puff ” a partir de botellas de plástico descartable.Fil: Giménez, Andrea F.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Sotelo Gasfrascoli, Lucía V.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Legizamón, Andrea M.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Coronel, Silvia C.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: López, Romina N.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Booth, Yanina M. R.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: López, Antonella E.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Lasala, César G.. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Peyrano, Felicitas. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Vallejos, Margarita. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Chaves, María Guadalupe. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Avanza, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; ArgentinaFil: Acevedo, Belén Andrea. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

Valor pronóstico de la ratio urea / creatinina en la insuficiencia cardiaca descompensada y su relación con el daño renal agudo

Introducción: El empeoramiento de la función renal es un índice de mal pronóstico en pacientes con insuficiencia cardiaca aguda (ICA). El cociente urea/creatinina (U/C) podría tener significación pronóstica en la ICA. Material y métodos: Estudio observacional, prospectivo, cuyo objetivo fue analizar el valor pronóstico del cociente U/C, determinado en las primeras 24-48 h del ingreso, en pacientes hospitalizados por ICA, así como su relación con el filtrado glomerular estimado (FGe) y el daño renal agudo (DRA). Resultados: Se incluyeron un total de 204 pacientes, con edad media de 79, 3 años. La mediana de FGe fue 55 ml/min/1, 73m2. En el análisis multivariante, un cociente U/C > 50 se asoció con una mayor probabilidad de DRA durante el ingreso (36, 5% vs. 21, 9%) y mortalidad por cualquier causa (odds ratio [OR] 2, 75) y por IC (OR 3, 50) durante el seguimiento. La elevación del cociente U/C fue pronóstica solo en los pacientes con FGe normales (mortalidad 4, 4% vs. 22%; p=0, 01). La combinación del cociente U/C con el FGe tuvo mayor capacidad predictiva de DRA que cada uno de ellos por separado (área bajo la curva 0, 718, intervalo de confianza al 95% 0, 643-0, 793; p<0, 001). Conclusiones: Un cociente U/C > 50 predice mortalidad a largo plazo en pacientes con FGe normal, y combinado con el FGe, mejora la identificación del riesgo de DRA, en pacientes ingresados por ICA. Dado lo simple de este biomarcador, sugerimos su uso sistemático en la clínica diaria. Background: Worsening renal function is associated with an adverse prognosis for patients with acute heart failure (AHF). Urea-creatinine ratio (U:C ratio) might be useful for measuring renal function and could help stratify patients with AHF. Material and methods: An observational and prospective study was conducted to analyse the prognostic value of the U:C ratio, measured during the first 24-28 hours of admission, for patients hospitalised for decompensated Heart failure, and its relationship with estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI). Results: The study included 204 patients, with a mean age of 79.3 years, and a median eGFR of 55 mL/min/1.73m2. In the multivariate analysis, an U:C ratio above the median (50) was related to the development of AKI (36.5% vs. 21.9%) and to increased mortality, both overall (OR 2.75) and by HF (OR 3.50) in long term. In combination with eGFR, the U:C ratio showed prognostic value in patients with normal eGFR (mortality of 4.4% for an U:C ratio = 50 vs. 22% for U:C ratio &gt; 50; p=0.01), as well as a better predictive capacity for AKI than each of them separately (AUC, 0.718; 95% CI 0.643-0.793; p&gt;.000). Conclusions: An U:C ratio &gt; 50 is a predictor of increased long-term mortality for patients hospitalised for decompensated HF and with normal eGFR. Given the simplicity of this biomarker, its use in clinical practice should be more systematic

Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study

[EN] Sepsis management remains one of the most important challenges in modern clinical practice. Rapid progression from sepsis to septic shock is practically unpredictable, hence the critical need for sepsis biomarkers that can help clinicians in the management of patients to reduce the proba-bility of a fatal outcome. Circulating nucleoproteins released during the inflammatory response to infection, including neutrophil extracellular traps, nucleosomes, and histones, and nuclear pro-teins like HMGB1, have been proposed as markers of disease progression since they are related to inflammation, oxidative stress, endothelial damage, and impairment of the coagulation response, among other pathological features. The aim of this work was to evaluate the actual potential for decision making/outcome prediction of the most commonly proposed chromatin-related bi-omarkers (i.e., nucleosomes, citrullinated H3, and HMGB1). To do this, we compared different ELISA measuring methods for quantifying plasma nucleoproteins in a cohort of critically ill pa-tients diagnosed with sepsis or septic shock compared to nonseptic patients admitted to the inten-sive care unit (ICU), as well as to healthy subjects. Our results show that all studied biomarkers can be used to monitor sepsis progression, although they vary in their effectiveness to separate sepsis and septic shock patients. Our data suggest that HMGB1/citrullinated H3 determination in plasma is potentially the most promising clinical tool for the monitoring and stratification of septic patients.This activity received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation program. C.R-M. thanks GVA for starting grant (GV/2018/127) and Spanish Ministry of Science and Innovation for research project (PID2020-119127RA-I00); J.B-G thanks ISCIII, AES2018 for iPFIS fellowship (IFI18/00015) and GVA for APOTI fellowship (APOTIP/2017/012); CG thanks Spanish Ministry of Universities for fellowship FPU18/03969; J.L.G-G and F.V.P thank INCLIVA, GVA and AES2016 and AES2019 (ISCIII) for starting grant (GV/2014/132), project PI16/01036 and PI19/00994 and project DTS17/00132 (co-financed by the ERDF). The project leading to these results has received funding from "la Caixa" Foundation (ID 100010434), under agreement CI18-0009. C.R-M., F.V.P. and A.M. thank Grand Challenges Canada. : We want to particularly acknowledge the patients and the INCLIVA Biobank (PT17/0015/0049; B.000768 ISCIII) integrated in the Valencian Biobanking Network and the Spanish National Biobanks Network for their collaboration.Beltrán-García, J.; Manclus Ciscar, JJ.; García-López, EM.; Carbonell, N.; Ferreres, J.; Rodríguez-Gimillo, M.; Garcés, C.... (2021). Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study. International Journal of Molecular Sciences. 22(18):1-15. https://doi.org/10.3390/ijms22189935115221

Valor pronóstico de la ratio urea / creatinina en la insuficiencia cardiaca descompensada y su relación con el daño renal agudo

Introducción: El empeoramiento de la función renal es un índice de mal pronóstico en pacientes con insuficiencia cardiaca aguda (ICA). El cociente urea/creatinina (U/C) podría tener significación pronóstica en la ICA. Material y métodos: Estudio observacional, prospectivo, cuyo objetivo fue analizar el valor pronóstico del cociente U/C, determinado en las primeras 24-48 h del ingreso, en pacientes hospitalizados por ICA, así como su relación con el filtrado glomerular estimado (FGe) y el daño renal agudo (DRA). Resultados: Se incluyeron un total de 204 pacientes, con edad media de 79,3 años. La mediana de FGe fue 55 ml/min/1,73m2. En el análisis multivariante, un cociente U/C > 50 se asoció con una mayor probabilidad de DRA durante el ingreso (36,5% vs. 21,9%) y mortalidad por cualquier causa (odds ratio [OR] 2,75) y por IC (OR 3,50) durante el seguimiento. La elevación del cociente U/C fue pronóstica solo en los pacientes con FGe normales (mortalidad 4,4% vs. 22%; p=0,01). La combinación del cociente U/C con el FGe tuvo mayor capacidad predictiva de DRA que cada uno de ellos por separado (área bajo la curva 0,718, intervalo de confianza al 95% 0,643-0,793; p<0,001). Conclusiones: Un cociente U/C > 50 predice mortalidad a largo plazo en pacientes con FGe normal, y combinado con el FGe, mejora la identificación del riesgo de DRA, en pacientes ingresados por ICA. Dado lo simple de este biomarcador, sugerimos su uso sistemático en la clínica diaria

Multiple approaches at admission based on lung ultrasound and biomarkers improves risk identification in COVID-19 patients

Background: Risk stratification of COVID-19 patients is fundamental to improving prognosis and selecting the right treatment. We hypothesized that a combination of lung ultrasound (LUZ-score), biomarkers (sST2), and clinical models (PANDEMYC score) could be useful to improve risk stratification. Methods: This was a prospective cohort study designed to analyze the prognostic value of lung ultrasound, sST2, and PANDEMYC score in COVID-19 patients. The primary endpoint was in-hospital death and/or admission to the intensive care unit. The total length of hospital stay, increase of oxygen flow, or escalated medical treatment during the first 72 h were secondary endpoints. Results: a total of 144 patients were included; the mean age was 57.5 ± 12.78 years. The median PANDEMYC score was 243 (52), the median LUZ-score was 21 (10), and the median sST2 was 53.1 ng/mL (30.9). Soluble ST2 showed the best predictive capacity for the primary endpoint (AUC = 0.764 (0.658–0.871); p = 0.001), towards the PANDEMYC score (AUC = 0.762 (0.655–0.870); p = 0.001) and LUZ-score (AUC = 0.749 (0.596–0.901); p = 0.002). Taken together, these three tools significantly improved the risk capacity (AUC = 0.840 (0.727–0.953); p = 0.001). Conclusions: The PANDEMYC score, lung ultrasound, and sST2 concentrations upon admission for COVID-19 are independent predictors of intra-hospital death and/or the need for admission to the ICU for mechanical ventilation. The combination of these predictive tools improves the predictive power compared to each one separately. The use of decision trees, based on multivariate models, could be useful in clinical practice. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

Absolute dimensions of solar-type eclipsing binaries. II. V636 Centauri: A 1.05 Msun primary with an active, cool, oversize 0.85 Msun secondary

The influence of stellar activity on the fundamental properties of stars around and below 1 Msun is not well understood. We aim to determine absolute dimensions and abundances for the solar-type detached eclipsing binary V636 Cen. The results are based on uvby light curves, uvby-beta standard photometry, radial velocity observations, and high-resolution spectra. Masses and radii that are precise to 0.5% have been established for the components of V636 Cen. The 0.85 Msun secondary component is moderately active with starspots and CaII H and K emission, and the 1.05 Msun primary shows signs of activity as well, but at a much lower level. We derive a [Fe/H] abundance of -0.20+/-0.08 and similar abundances for Si, Ca, Ti, V, Cr, Co, and Ni. Corresponding solar-scaled stellar models are unable to reproduce V636 Cen, especially its secondary component, which is ~10% larger and ~400 K cooler than predicted. Models adopting significantly lower mixing-length parameters l/H_p remove these discrepancies, seen also for other solar-type binary components. For the observed [Fe/H], Claret models for l/H_p = 1.4 (primary) and 1.0 (secondary) reproduce the components of V636 Cen at a common age of 1.35 Gyr. V636 Cen and 10 other well-studied inactive and active solar-type binaries suggest that chromospheric activity, and its effect on envelope convection, is likely to cause radius and temperature discrepancies, which can be removed by adjusting the model mixing length parameters downwards. Noting this, the sample may also lend support to theoretical 2D radiation hydrodynamics studies, which predict a slight decrease of the mixing length parameter with increasing temperature/mass for inactive main sequence stars.Comment: Accepted for publication in Astronomy and Astrophysic