Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis

Cerebral edema (CED) is a severe complication of acute ischemic stroke. There is uncertainty regarding the predictors for the development of CED after cerebral infarction. We aimed to determine which baseline clinical and radiological parameters predict development of CED in patients treated with intravenous thrombolysis. We used an image-based classification of CED with 3 degrees of severity (less severe CED 1 and most severe CED 3) on postintravenous thrombolysis imaging scans. We extracted data from 42 187 patients recorded in the SITS International Register (Safe Implementation of Treatments in Stroke) during 2002 to 2011. We did univariate comparisons of baseline data between patients with or without CED. We used backward logistic regression to select a set of predictors for each CED severity. CED was detected in 9579/42 187 patients (22.7%: 12.5% CED 1, 4.9% CED 2, 5.3% CED 3). In patients with CED versus no CED, the baseline National Institutes of Health Stroke Scale score was higher (17 versus 10; P<0.001), signs of acute infarct was more common (27.9% versus 19.2%; P<0.001), hyperdense artery sign was more common (37.6% versus 14.6%; P<0.001), and blood glucose was higher (6.8 versus 6.4 mmol/L; P<0.001). Baseline National Institutes of Health Stroke Scale, hyperdense artery sign, blood glucose, impaired consciousness, and signs of acute infarct on imaging were independent predictors for all edema types. The most important baseline predictors for early CED are National Institutes of Health Stroke Scale, hyperdense artery sign, higher blood glucose, decreased level of consciousness, and signs of infarct at baseline. The findings can be used to improve selection and monitoring of patients for drug or surgical treatment

Awareness of cognitive abilities in the execution of activities of daily living after acquired brain injury: an evaluation protocol

Introduction One of the main limitations that can be observed after acquired brain injury (ABI) is the alteration of the awareness of the deficits that can occur in the cognitive skills necessary for performing activities of daily living (ADL). According to the Dynamic Comprehensive Model of Awareness (DCMA), consciousness is composed of offline component, which contains the information stored about characteristics of the tasks and stable beliefs about one’s own capabilities and online awareness, which is activated in the context of the performance of a specific task. The main objective of this project was to generate and validate a detailed cognitive assessment protocol within the context of ADL to evaluate the components of DCMA. Methods and analysis The proposed protocol consists of two ecological tools: The Cog-Awareness ADL Scale to measure offline component and the Awareness ADL-task: Basic and Instrumental ADL performance-based test to measure online awareness. The aim is to identify the presence of cognitive deficits and anosognosia in patients with ABI within the context of everyday life activities. These two measures will be administered to a group of patients with ABI. In addition, these participants will complete another series of classic tests on anosognosia and cognitive functions in order to find the convergent validity of the two tests proposed in this protocol. The external validity of the Cog-Awareness ADL Scale and the relationships between awareness components within the same ADL domain will be also analysed. Ethics and dissemination This study was approved by the Ethics Committee of Biomedical Research of Andalusia, on 13 January /2017 (Proceeding 1/2017). All participants are required to provide written informed consent. The findings from this will be disseminated via scientific publication.Spanish Ministry of Economy and Competitiveness PSI2016-80331-PUniversity of MalagaUniversity of Vic - Central University of Catalonia (UVic-UCC

Scaling Equipment Effect on Technical–Tactical Actions in U-13 Basketball Players: A Maturity Study

The aim of this study was to analyse the performance of technical–tactical actions in two different types of tournaments and the influence of biological age on the performance of young basketball players. Thirty-seven under-13 male basketball players (age = 12.91 ± 0.57 years) were selected from four southeast Spanish teams to participate in two different tournaments on two consecutive days. The following technical–tactical variables were analysed: (a) Ball Obtained; (b) Ball Handler Player Actions; (c) Ball Handler Player Finished Actions; and (d) Ball Handler Shooting Performance. The results showed that reduced basket height and a closer three-point line promoted a higher number of balls obtained, 1 vs. 1 situations, finished ball player actions, shots, and the efficacy of offence phases. There was a significant increase in the number of balls obtained, 1 vs. 1 situations played, the number of plays finished with a lay-up or shot, number of received personal fouls, number of plays finished in 1 vs. 2, and those finished in equality and inferiority with a high defence opposition. The modified version presented a higher number of technical–tactical actions in Late Maturity players. The authors of this study believe that it is necessary to conduct more experimental studies and use bio-banding strategies in young basketball competitions.This research was funded by the Basket 2.0 project (No. 21076/PDC/19) granted by Fundación Séneca—Agencia de Ciencia y Tecnologia de la Región de Murcia and Consejo Superior de Deportes (19/UPB/21)

Mandibular Third Molar Impaction and Bone Change Distal to the Second Molar: A Panoramic Radiographic Study

Background: The mandibular third molar is the most frequently impacted tooth. An impacted mandibular third molar (IMTM) can have negative consequences on the adjacent mandibular second molar (MSM), such as bone loss. An IMTM can be identified using orthopantomography (OPG). Our objective is to compare changes in bone level distal to the mandibular second molar (MSM) in patients with an extracted IMTM versus non-extracted IMTM using OPG. Methods: In this retrospective case-control study, 160 orthopantomograms (OPGs) of 80 patients who attended Dental Hospital of the University of Barcelona (HOUB) were randomly selected. Participants were stratified into a study group and control group. Results: Males and females experienced bone gain in the study group and bone loss in the control group. However, the difference in bone-level change was not statistically significant regarding gender in the study group. Within the study group, the age group of 29-39 years demonstrated significant (p-value = 0.042) bone gain after extraction compared to other age groups. However, the control group demonstrated bone loss in all age groups in which the difference is not statistically significant (p-value 0.794). Conclusions: Bone improvements distal to the MSM were observed after the extraction of an IMTM compared to when an IMTM was not extracted

Decreased circulating Fas ligand in patients with familial combined hyperlipidemia or carotid atherosclerosis Normalization by atorvastatin

AbstractObjectivesWe sought to study whether patients with familial combined hyperlipidemia (FCH) or carotid atherosclerosis have modified circulating solubilized Fas ligand (sFasL) levels, as well as the potential modifications by atorvastatin. We also examined the effect of atorvastatin on FasL expression and sFasL release in cytokine-stimulated cultured human endothelial cells (ECs).BackgroundIn normal situations, FasL is expressed in most cells, including ECs. Proinflammatory stimuli can downregulate its expression in ECs and facilitate the vascular infiltration of inflammatory cells.MethodsWe have measured sFasL plasma levels (by ELISA) in 58 patients with FCH, 14 normocholesterolemic patients with carotid atherosclerosis, and 15 healthy volunteers. We analyzed FasL expression (by Western blot analysis) and sFasL release in cultured ECs stimulated with tumor necrosis factor (TNF)-alpha.ResultsSolubilized FasL levels were decreased in hyperlipidemic patients (49 pg/ml), as compared with healthy volunteers (123 pg/ml, p < 0.0001). Patients were randomized to atorvastatin (n = 28) or bezafibrate (n = 30) during 12 months. Atorvastatin treatment increased sFasL concentrations (111 pg/ml, p < 0.0001), reaching normal values. However, treatment with bezafibrate only marginally affected sFasL (85 pg/ml, p < 0.05). Solubilized FasL was also diminished in patients with carotid atherosclerosis (39 pg/ml), and intensive treatment with atorvastatin normalized sFasL levels (90 pg/ml, p = 0.02). Finally, atorvastatin prevented the diminution of FasL expression and sFasL release elicited by TNF-alpha in cultured ECs.ConclusionsPatients with FCH or carotid atherosclerosis have decreased circulating sFasL levels, probably indicating endothelial dysfunction, but treatment with atorvastatin restored normal blood levels. These data provide a novel effect of atorvastatin and add support for the well-known anti-inflammatory properties of statins

Animal Models of Cardiovascular Diseases

Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases

Proteomic approach in the search of new cardiovascular biomarkers

Proteomic approach in the search of new cardiovascular biomarkers With the increasing incidence of cardiovascular diseases worldwide, specifically atherosclerosis and heart failure, the search for novel biomarkers remains a priority. As opposed to complex diagnostic techniques that may not be suitable to be applied to the wider population, biomarkers are useful for population screening. The search for novel biomarkers is based on knowledge of the molecular and cellular processes that take place in the development of a specific disease. Atherosclerosis and heart failure are characterized by a long period of silent disease progression, allowing early diagnosis and the potential of early therapeutic intervention. The use of the so-called proteomic techniques allows not only protein identification but partial characterization, which includes expression and also post-translational modification of these proteins. This allows for the discovery of previously unknown proteins involved in cardiovascular diseases, including some that may be suitable to be used as biomarkers. However, to approach this issue, we have to overcome difficulties such as tissue heterogeneity (vessel wall or myocardium) and the lack of fresh human samples. We discuss the proteomic study of human plaques, secreted proteins by pathologic and normal vessel wall, and left ventricular hypertrophy as potential sources of new biologic markers of cardiovascular disease

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas alpha-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.We thank Simon Bartlett for language and scientific editing. This study was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2016-80843-R, BIO2012-37926 and BIO2015-67580-P), Fondo de Investigaciones Sanitarias ISCiii-FEDER (PRB2) (IPT13/0001, ProteoRed, Redes RIC RD12/0042/00038 and RD12/0042/0056, Biobancos RD09/0076/00101 and CA12/00371), Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), and FRIAT. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI

CD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (−) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesionsThis work was funded by Spanish Government through a Plan Nacional (CTQ2011–27268), FEDER funds through the Fondo de Investigación Sanitaria (PI10/00072, PI13/00051, PI13/00395, PI13/00802, PI14/00883 and PI14/00386), CIBERDEM group, RETICS RD12/0042/0038, Programa Miguel Servet (CP10/00479) and cvREMOD CENIT project (CEN-20091044), the Basque Government through Etortek 2011 (IE11–301), and Fundacion Lilly, Spanish Society of Atherosclerosis, Spanish Society of Nephrology and Fundacion Renal Iñigo Alvarez de Toled