Publications by authors named "Carolina Sánchez"

40 Publications

Generation of Chloroplast Molecular Markers to Differentiate and Its Hybrids as a First Approach to Its Reintroduction in Rapa Nui (Easter Island).

Plants (Basel) 2021 Feb 10;10(2). Epub 2021 Feb 10.

Advanced Genomics Core, Universidad Mayor, Santiago 8580745, Chile.

is an endemic tree of Rapa Nui with religious and cultural relevance that despite being extinct in the wild, still persists in botanical gardens and private collections around the world. The authenticity of some toromiro trees has been questioned because the similarities among hybrid lines leads to misclassification of the species. The conservation program of toromiro has the objective of its reinsertion into Rapa Nui, but it requires the exact genotyping and certification of the selected plants in order to efficiently reintroduce the species. In this study, we present for the first time the complete chloroplast genome of and four other specimens, which were sequenced de-novo and assembled after mapping the raw reads to a chloroplast database. The length of the chloroplast genomes ranges from 154,239 to 154,473 bp. A total of 130-143 simple sequence repeats (SSR) loci and 577 single nucleotide polymorphisms (SNPs) were identified.
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http://dx.doi.org/10.3390/plants10020342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916652PMC
February 2021

Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department.

Emergencias 2020 Nov;32(6):386-394

Área de Urgencias, Hospital Clinic, Universitat de Barcelona, España.

Objectives: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease 2019 (COVID-19).

Material And Methods: Retrospective observational study of consecutive patients who came to the ED over a period of 2 months and were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given in the ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit were compared, and factors associated with revisits were explored.

Results: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99; P = .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63; P = .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06; P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21, P = .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67; P = .002) and fever (OR, 4.73; 95% CI, 1.99-11.27; P = .001).

Conclusion: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization.
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November 2020

Activation of OX40 and CD27 Costimulatory Signalling in Sheep through Recombinant Ovine Ligands.

Vaccines (Basel) 2020 Jun 22;8(2). Epub 2020 Jun 22.

Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, 28130 Madrid, Spain.

Members of the tumour necrosis factor (TNF) superfamily OX40L and CD70 and their receptors are costimulating signalling axes critical for adequate T cell activation in humans and mice but characterisation of these molecules in other species including ruminants is lacking. Here we cloned and expressed the predicted ovine orthologues of the receptors OX40 and CD27, as well as soluble recombinant forms of their potential ovine ligands, OX40L and CD70. Using biochemical and immunofluorescence analyses, we show that both signalling axes are functional in sheep. We show that oligomeric recombinant ligand constructs are able to induce signalling through their receptors on transfected cells. Recombinant defective human adenoviruses were constructed to express the soluble forms of OX40L and CD70. Both proteins were detected in the supernatant of adenovirus-infected cells and shown to activate NF-κB signalling pathway through their cognate receptor. These adenovirus-secreted OX40L and CD70 forms could also activate ovine T cell proliferation and enhance IFN-γ production in CD4 and CD8 T cells. Altogether, this study provides the first characterisation of the ovine costimulatory OX40L-OX40 and CD70-CD27 signalling axes, and indicates that their activation in vivo may be useful to enhance vaccination-induced immune responses in sheep and other ruminants.
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http://dx.doi.org/10.3390/vaccines8020333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350415PMC
June 2020

Addition of a Viral Immunomodulatory Domain to Etanercept Generates a Bifunctional Chemokine and TNF Inhibitor.

J Clin Med 2019 Dec 20;9(1). Epub 2019 Dec 20.

Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Cantoblanco, 28049 Madrid, Spain.

The inhibition of tumor necrosis factor (TNF) through the use of either antibodies or soluble receptors is a highly effective strategy for the clinical control of chronic inflammatory conditions such as rheumatoid arthritis. Different viruses have similarly exploited this concept by expressing a set of specifically tailored secreted TNF decoy receptors to block host inflammatory responses. Poxviruses have been shown to encode at least two distinct molecules, termed Cytokine response modifier D (CrmD) and CrmB, in which a TNF inhibitor is combined with a chemokine inhibitor on the same molecule. The ectromelia virus CrmD protein was found to be a critical determinant of virulence in vivo, being able to control local inflammation to allow further viral spread and the establishment of a lethal infection. Strikingly, both the TNF and the chemokine inhibitory domains are required for the full activity of CrmD, suggesting a model in which inhibition of TNF is supported by the concomitant blockade of a reduced set of chemokines. Inspired by this model, we reasoned that a similar strategy could be applied to modify the clinically used human TNF receptor (etanercept), producing a generation of novel, more effective therapeutic agents. Here we show the analysis of a set of fusion proteins derived from etanercept by addition of a viral chemokine-binding protein. A bifunctional inhibitor capable of binding to and blocking the activity of TNF as well as a set of chemokines is generated that is active in the prevention of arthritis in a murine disease model.
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http://dx.doi.org/10.3390/jcm9010025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020083PMC
December 2019

NOTCH3 Gene Mutation in a Chilean Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Family.

J Stroke Cerebrovasc Dis 2020 Feb 6;29(2):104530. Epub 2019 Dec 6.

Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago, Chile; Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address:

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke disorder caused by mutations in the NOTCH3 gene. We report the first Chilean CADASIL family with complete radiological and histological studies.

Methods: The family tree was constructed from an autopsy-confirmed confirmed patient, and includes 3 generations. We performed clinical, pathologic, genetic, and radiologic examinations on members of a family with CADASIL.

Results: In the second generation, findings compatible with CADASIL were identified in 6 individuals, all of whom had a missense mutation in exon 3 (c.268C>T) resulting in an arginine to cysteine amino acid substitution at position 90 (R90C). In the third generation, a missense mutation was detected in one of the 4 asymptomatic individuals.

Conclusions: There are similarities in clinical presentation between this family and previously described Asian and European series with R90C mutations. Detecting genotypes with a gain or loss of cysteine residues opens the door to future gene transfection-based therapies.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104530DOI Listing
February 2020

Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study.

Authors:
Òscar Miró Joan Padrosa Koji Takagi Étienne Gayat Víctor Gil Pere Llorens Francisco Javier Martín-Sánchez Pablo Herrero-Puente Javier Jacob María Mir Montero Josep Tost María Pilar López Díez Lissete Traveria Raquel Torres-Gárate María Isabel Alonso Carmen Agüera Amparo Valero Patricia Javaloyes W Frank Peacock Héctor Bueno Alexandre Mebazaa Marta Fuentes Cristina Gil Héctor Alonso Pablo Garmila Guillermo Llopis García María Cecilia Yáñez-Palma Sergio Iglesias López Rosa Escoda Carolina Xipell Carolina Sánchez Josep María Gaytan María José Pérez-Durá Eva Salvo José Pavón Antonio Noval José Manuel Torres María Luisa López-Grima Amparo Valero Marian Ángeles Juan Alfons Aguirre Julián Errasti Morales Silvia Mínguez Masó María Isabel Alonso Francisco Ruiz José Miguel Franco Ana Belén Mecina Josep Tost Susana Sánchez Virginia Carbajosa Pascual Piñera José Andrés Sánchez Nicolás Raquel Torres Garate Aitor Alquezar Miguel Alberto Rizzi Sergio Herrera Alex Roset Irene Cabello Fernando Richard José María Álvarez Pérez María Pilar López Diez Joaquín Vázquez Álvarez Belén Prieto García María García García yMarta Sánchez González Patricia Javaloyes Víctor Marquina Inmaculada Jiménez Néstor Hernández Benjamín Brouzet Sergio Ramos Ana López Juan Antonio Andueza Rodolfo Romero Martín Ruíz Roberto Calvache María Teresa Lorca Luis Calderón Beatriz Amores Arriaga Beatriz Sierra Enrique Martín Mojarro Lisette Travería Bécquer Guillermo Burillo Lluís Llauger García Gerard Corominas LaSalle Carmen Agüera Urbano Ana Belén García Soto Elisa Delgado Padial Ester Soy Ferrer Manuel Garrido Francisco Javier Lucas Rut Gaya Carlos Bibiano María Mir Beatriz Rodríguez Natalia Sánchez José Luis Carballo Esther Rodríguez-Adrada Belén Rodríguez

Eur J Intern Med 2019 Dec 23;70:24-32. Epub 2019 Aug 23.

Hospital Rey Juan Carlos de Mostoles de Madrid, Spain.

Objective: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation.

Methods: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (<6/6-10/11-15/>15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH <6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units.

Results: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4-11): 2934 (34.3%) had a LOH <6 days, 3184 (37.2%) 6-10 days, 1287 (15.0%) 11-15 days, and 1158 (13.5%) >15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0-64.9) when LOH was 11-15 days, and by 72.0% (95%CI = 42.6-107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4-36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk.

Conclusions: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments.
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http://dx.doi.org/10.1016/j.ejim.2019.08.007DOI Listing
December 2019

Identification of lupeol produced by (Kunth) H. Rob. leaf callus culture.

Nat Prod Res 2021 Feb 8;35(3):503-507. Epub 2019 Jul 8.

Centro de Investigaciones Biotecnológicas del Ecuador, ESPOL Polytechnic University, Escuela Superior Politécnica del Litoral, ESPOL, Guayaquil, Ecuador.

The lupeol detection in callus of (Kunth) H. Rob. leaves is discussed. Leaf segments previously treated with sodium hypochlorite, ethanol, and distilled water were placed in MS basal medium (Murashige and Skoog) for 7 days. Next, callus induction were done in two complemented MS medium for 6 weeks. Then, callus propagation were performed in MS medium supplemented with 1.0 mg/L of benzylaminopurine (BAP) and 0.5 mg/L of 2,4-dichlorophenoxyacetic acid (2,4-D) for 50 days. Fresh callus were extracted every 10 days in an ultrasonic bath using ethyl acetate (1.0 g/10 mL). The identification was carried out by Gas Chromatography-Mass Spectrometry (GC-MS) using selected ion monitoring (SIM) acquisition mode with characteristic ions of lupeol. The results obtained indicate the occurrence of lupeol in callus extract after twenty days of proliferation. These findings could be use in subsequent scale-up studies for biomass production containing this active compound in order to replace conventional methods.
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http://dx.doi.org/10.1080/14786419.2019.1636239DOI Listing
February 2021

Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes.

Eur J Heart Fail 2019 11 18;21(11):1353-1365. Epub 2019 Jun 18.

Emergency Department, Short-Stay Unit and Home Hospitalization, Hospital General de Alicante, Alicante, Spain.

Objective: To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED).

Methods And Results: Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1-year all-cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in-hospital all-cause mortality, prolonged hospitalisation, 7-day post-discharge ED revisit for AHF and 30-day post-discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm + wet, 1929 (17.1%) cold + wet, 675 (6.0%) warm + dry, and 99 (0.9%) cold + dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm + wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1-year mortality was 30.8%, and compared to warm + dry, the adjusted hazard ratios were significantly increased for cold + wet (1.660; 95% confidence interval 1.400-1.968) and cold + dry (1.672; 95% confidence interval 1.189-2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in-hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk.

Conclusions: Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival.
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http://dx.doi.org/10.1002/ejhf.1502DOI Listing
November 2019

Effect of risk of malnutrition on 30-day mortality among older patients with acute heart failure in Emergency Departments.

Eur J Intern Med 2019 Jul 7;65:69-77. Epub 2019 May 7.

Hospital Sant Pau i Santa Tecla, Tarragona, Spain.

Background: Little is known about the prevalence and impact of risk of malnutrition on short-term mortality among seniors presenting with acute heart failure (AHF) in emergency setting. The objective was to determine the impact of risk of malnutrition on 30-day mortality risk among older patients who attended in Emergency Departments (EDs) for AHF.

Material And Methods: We performed a secondary analysis of the OAK-3 Registry including all consecutive patients ≥65 years attending in 16 Spanish EDs for AHF. Risk of malnutrition was defined by the Mini Nutritional Assessment Short Form (MNA-SF) < 12 points. Unadjusted and adjusted logistic regression models were used to assess the association between risk of malnutrition and 30-day mortality.

Results: We included 749 patients (mean age: 85 (SD 6); 55.8% females). Risk of malnutrition was observed in 594 (79.3%) patients. The rate of 30-day mortality was 8.8%. After adjusting for MEESSI-AHF risk score clinical categories (model 1) and after adding all variables showing a significantly different distribution among groups (model 2), the risk of malnutrition was an independent factor associated with 30-day mortality (adjusted OR by model 1 = 3.4; 95%CI 1.2-9.7; p = .020 and adjusted OR by model 2 = 3.1; 95%CI 1.1-9.0; p = .033) compared to normal nutritional status.

Conclusions: The risk of malnutrition assessed by the MNA-SF is associated with 30-day mortality in older patients with AHF who were attended in EDs. Routine screening of risk of malnutrition may help emergency physicians in decision-making and establishing a care plan.
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http://dx.doi.org/10.1016/j.ejim.2019.04.014DOI Listing
July 2019

Subversion of natural killer cell responses by a cytomegalovirus-encoded soluble CD48 decoy receptor.

PLoS Pathog 2019 04 4;15(4):e1007658. Epub 2019 Apr 4.

Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.

Throughout evolution, cytomegaloviruses (CMVs) have been capturing genes from their hosts, employing the derived proteins to evade host immune defenses. We have recently reported the presence of a number of CD48 homologs (vCD48s) encoded by different pathogenic viruses, including several CMVs. However, their properties and biological relevance remain as yet unexplored. CD48, a cosignaling molecule expressed on the surface of most hematopoietic cells, modulates the function of natural killer (NK) and other cytotoxic cells by binding to its natural ligand 2B4 (CD244). Here, we have characterized A43, the vCD48 exhibiting the highest amino acid sequence identity with host CD48. A43, which is encoded by owl monkey CMV, is a soluble molecule released from the cell after being proteolytically processed through its membrane proximal region. A43 is expressed with immediate-early kinetics, yielding a protein that is rapidly detected in the supernatant of infected cells. Remarkably, surface plasmon resonance assays revealed that this viral protein binds to host 2B4 with high affinity and slow dissociation rates. We demonstrate that soluble A43 is capable to abrogate host CD48:2B4 interactions. Moreover, A43 strongly binds to human 2B4 and prevents 2B4-mediated NK-cell adhesion to target cells, therefore reducing the formation of conjugates and the establishment of immunological synapses between human NK cells and CD48-expressing target cells. Furthermore, in the presence of this viral protein, 2B4-mediated cytotoxicity and IFN-γ production by NK cells are severely impaired. In summary, we propose that A43 may serve as a functional soluble CD48 decoy receptor by binding and masking 2B4, thereby impeding effective NK cell immune control during viral infections. Thus, our findings provide a novel example of the immune evasion strategies developed by viruses.
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http://dx.doi.org/10.1371/journal.ppat.1007658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448830PMC
April 2019

Insights into ligand binding by a viral tumor necrosis factor (TNF) decoy receptor yield a selective soluble human type 2 TNF receptor.

J Biol Chem 2019 03 5;294(13):5214-5227. Epub 2019 Feb 5.

From the Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain

Etanercept is a soluble form of the tumor necrosis factor receptor 2 (TNFR2) that inhibits pathological tumor necrosis factor (TNF) responses in rheumatoid arthritis and other inflammatory diseases. However, besides TNF, etanercept also blocks lymphotoxin-α (LTα), which has no clear therapeutic value and might aggravate some of the adverse effects associated with etanercept. Poxviruses encode soluble TNFR2 homologs, termed viral TNF decoy receptors (vTNFRs), that display unique specificity properties. For instance, cytokine response modifier D (CrmD) inhibits mouse and human TNF and mouse LTα, but it is inactive against human LTα. Here, we analyzed the molecular basis of these immunomodulatory activities in the ectromelia virus-encoded CrmD. We found that the overall molecular mechanism to bind TNF and LTα from mouse and human origin is fairly conserved in CrmD and dominated by a groove under its 50s loop. However, other ligand-specific binding determinants optimize CrmD for the inhibition of mouse ligands, especially mouse TNF. Moreover, we show that the inability of CrmD to inhibit human LTα is caused by a Glu-Phe-Glu motif in its 90s loop. Importantly, transfer of this motif to etanercept diminished its anti-LTα activity in >60-fold while weakening its TNF-inhibitory capacity in 3-fold. This new etanercept variant could potentially be used in the clinic as a safer alternative to conventional etanercept. This work is the most detailed study of the vTNFR-ligand interactions to date and illustrates that a better knowledge of vTNFRs can provide valuable information to improve current anti-TNF therapies.
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http://dx.doi.org/10.1074/jbc.RA118.005828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442024PMC
March 2019

Care Bundles after Discharging Patients with Chronic Obstructive Pulmonary Disease Exacerbation from the Emergency Department.

Med Sci (Basel) 2018 Aug 7;6(3). Epub 2018 Aug 7.

Emergencies Group: Processes and Pathologies, Institut d'Investigacions Biomèdiques August Pi i Sunyer, C/Rosselló 149, 08036 Barcelona, Spain.

Chronic obstructive pulmonary disease (COPD) is the second leading cause of emergency department (ED) admissions to hospital, and nearly a third of patients with acute exacerbation (AE) of COPD are re-admitted to hospital within 28 days after discharge. It has been suggested that nearly a third of COPD admissions could be avoided through the implementation of evidence-based care interventions. A COPD discharge bundle is a set of evidence-based practices, aimed at improving patient outcomes after discharge from AE COPD; body of evidence supports the usefulness of discharge care bundles after AE of COPD, although there is a lack of consensus of what interventions should be implemented. On the other hand, the implementation of those interventions also involves different challenges. Important care gaps remain regarding discharge care bundles for patients with acute exacerbation of COPD discharged from EDs There is an urgent need for investigations to guide future implementation of care bundles for those patients discharged from EDs.
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http://dx.doi.org/10.3390/medsci6030063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164584PMC
August 2018

Effects on short term outcome of non-invasive ventilation use in the emergency department to treat patients with acute heart failure: A propensity score-based analysis of the EAHFE Registry.

Eur J Intern Med 2018 07 21;53:45-51. Epub 2018 Mar 21.

Emergency Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.

Objective: To assess the effects of non-invasive ventilation (NIV) in emergency department (ED) patients with acute heart failure (AHF) on short term outcomes.

Methods: Patients from the EAHFE Registry (a multicenter, observational, multipurpose, cohort-designed database including consecutive AHF patients in 41 Spanish EDs) were grouped based on NIV treatment (NIV+ and NIV-groups). Using propensity score (PS) methodology, we identified two subgroups of patients matched by 38 covariates and compared regarding 30-day survival (primary outcome). Interaction was investigated for age, sex, ischemic cardiomyopathy, chronic obstructive pulmonary disease, AHF precipitated by an acute coronary syndrome (ACS), AHF classified as hypertensive or acute pulmonary edema (APE), and systolic blood pressure (SBP). Secondary outcomes were intensive care unit (ICU) admission; mechanical ventilation; in-hospital, 3-day and 7-day mortality; and prolonged hospitalization (>7 days).

Results: Of 11,152 patients from the EAHFE (age (SD): 80 (10) years; 55.5% women), 718 (6.4%) were NIV+ and had a higher 30-day mortality (HR = 2.229; 95%CI = 1.861-2.670) (p < 0.001). PS matching provided 2 groups of 490 patients each with no significant differences in 30-day mortality (HR = 1.239; 95%CI = 0.905-1.696) (p = 0.182). Interaction analysis suggested a worse effect of NIV on elderly patients (>85 years, p < 0.001), AHF associated with ACS (p = 0.045), and SBP < 100 mmHg (p < 0.001). No significant differences were found in the secondary endpoints except for more prolonged hospitalizations in NIV+ patients (OR = 1.445; 95%CI = 1.122-1.862) (p = 0.004).

Conclusion: The use of NIV to treat AHF in ED is not associated with improved mortality outcomes and should be cautious in old patients and those with ACS and hypotension.
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http://dx.doi.org/10.1016/j.ejim.2018.03.008DOI Listing
July 2018

Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis.

Neurobiol Aging 2018 04 29;64:123-138. Epub 2017 Dec 29.

Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, USA; Harvard School of Public Health, Boston, MA, USA. Electronic address:

The occurrence of mutations of TDP-43, FUS, and C9ORF72 in amyotrophic lateral sclerosis (ALS) suggests pathogenic alterations to RNA metabolism and specifically to microRNA (miRNA) biology. Moreover, several ALS-related proteins impact stress granule dynamics affecting miRNA biogenesis and cellular miRNA levels. miRNAs are present in different biological fluids and have been proposed as potential biomarkers. Here we used next-generation sequencing to perform a comparative analysis of the expression profile of circulating miRNAs in the serum of 2 mutant superoxide dismutase 1 transgenic mice. Top hit candidates were then validated using quantitative real-time polymerase chain reaction, confirming significant changes for 6 miRNAs. In addition, one of these miRNAs was also altered in mutant TDP-43 mice. Then, we tested this set of miRNAs in the serum from sporadic ALS patients, observing a significant deregulation of hsa-miR-142-3p and hsa-miR-1249-3p. A negative correlation between the revised ALS functional rating scale and hsa-miR-142-3p levels was found. Bioinformatics analysis of the regulatory network governed by hsa-miR-142-3p identified TDP-43 and C9orf72 as possible targets, suggesting a connection with ALS pathogenesis. This study identifies miRNAs that are altered in ALS that may serve as potentials biomarkers.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.12.020DOI Listing
April 2018

[Prehospital emergency care of patients with acute heart failure in Spain: the SEMICA study (Emergency Medical Response Systems for Patients with Acute Heart Failure)].

Emergencias 2017 07;29(4):223-230

Servicio de Medicina Preventiva, Hospital Clínico San Carlos, Madrid; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Universidad Complutense de Madrid, España.

Objectives: To study the means of emergency transport used to bring patients with acute heart failure (AHF) to hospital emergency departments (EDs) and explore associations between factors, type of transport, and prehospital care received.

Material And Methods: We gathered the following information on patients treated for AHF at 34 Spanish hospital EDs: means of transport used (medicalized ambulance [MA], nonmedicalized ambulance [NMA], or private vehicle) and treatments administered before arrival at the hospital. Twenty-seven independent variables potentially related to type of transport used were also studied. Indicators of AHF severity were triage level assigned in the ED, need for admission, need for intensive care, in-hospital mortality, and 30-day mortality.

Results: A total of 6106 patients with a mean (SD) age of 80 years were included; 56.5% were women, 47.2% arrived in PVs, 37.8% in NMAs, and 15.0% in MAs. Use of an ambulance was associated with female sex, age over 80 years, chronic obstructive pulmonary disease, a history of AHF, functional dependency, New York Heart Association class III-IV, sphincteral incontinence, labored breathing, orthopnea, cold skin, and sensory depression or restlessness. Assignment of a MA was directly associated with living alone, a history of ischemic heart disease, cold skin, sensory depression or restlessness, and high temperature; it was inversely associated with a history of falls. The rates of receipt of prehospital treatments and AHF severity level increased with use of MAs vs. NMAs vs. PV. Seventy-three percent of patients transported in MAs received oxygen, 29% received a diuretic, 13.5% a vasodilator, and 4.7% noninvasive ventilation.

Conclusion: Characteristics of the patient with AHF are associated with the assignment of type of transport to a hospital ED. Assignment appears to be related to severity. Treatment given during MA transport could be increased.
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July 2017

Short-term reconsultation, hospitalisation, and death rates after discharge from the emergency department in patients with acute heart failure and analysis of the associated factors. The ALTUR-ICA Study.

Med Clin (Barc) 2018 03 21;150(5):167-177. Epub 2017 Jul 21.

Servicio de Urgencias, Corta Estancia y Hospitalización a Domicilio, Hospital General de Alicante, Departamento de Medicina Clínica, Universidad Miguel Hernández, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-FISABIO), Alicante, España. Electronic address:

Background And Objectives: The aim of this study was to define the following in patients with acute heart failure (AHF) discharged directly from accident and emergency (A&E): rates of reconsultation to A&E and hospitalisation for AHF, and all-cause death at 30 days, rate of combined event at 7 days and the factors associated with these rates.

Patients And Method: The study included patients consecutively diagnosed with AHF during 2 months in 27 Spanish A&E departments who were discharged from A&E without hospitalisation. We collected 43 independent variables, monitored patients for 30 days and evaluated predictive factors for adverse events using Cox regression analysis.

Results: We evaluated 785 patients (78±9) years, 54.7% women). The rates of reconsultation, hospitalisation, and death at 30 days and the combined event at 7 days were: 26.1, 15.7, 1.7 and 10.6%, respectively. The independent factors associated with reconsultation were no endovenous diuretics administered in A&E (HR 2.86; 95% CI 2.01-4.04), glomerular filtration rate (GFR)<60ml/min/m (1.94; 1.37-2.76) and previous AHF episodes (1.48; 1.02-2.13); for hospitalisation these factors were no endovenous diuretics in A&E (2.97; 1.96-4.48), having heart valve disease (1.61; 1.04-2.48), blood oxygen saturation at arrival to A&E<95% (1.60; 1.06-2.42); and for the combined event no endovenous diuretics in A&E (3.65; 2.19-6.10), GFR<60ml/min/m (2.22; 1.31-3.25), previous AHF episodes (1.95; 1.04-3.25), and use of endovenous nitrates (0.13; 0.02-0.99).

Conclusion: This is the first study in Spain to describe the rates of adverse events in patients with AHF discharged directly from A&E and define the associated factors. These data should help establish the most adequate approaches to managing these patients.
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http://dx.doi.org/10.1016/j.medcli.2017.06.004DOI Listing
March 2018

Draft Genome Sequences of Five Species Isolated from the Gut of Patients with Suspected Infection.

Genome Announc 2017 May 18;5(20). Epub 2017 May 18.

Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Santiago, Chile

We present draft genome sequences of five species from patients suspected of infection. Genome completeness was confirmed by presence of bacterial orthologs (97%). Gene searches using Hidden-Markov models revealed that the isolates harbor between seven and 11 genes involved in antibiotic resistance to tetracyclines, beta-lactams, and vancomycin.
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http://dx.doi.org/10.1128/genomeA.00379-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477334PMC
May 2017

A Useful Allene for the Stereoselective Synthesis of Protected Quaternary 2-Amino-2-vinyl-1,3-diols.

J Org Chem 2017 02 25;82(3):1851-1855. Epub 2017 Jan 25.

Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Facultat de Química, Universitat de Barcelona , Martí i Franquès 1, Barcelona 08028, Spain.

Treatment of readily available allene 1 with CyBH followed by addition of an aldehyde led to quaternary protected 2-amino-2-vinyl-1,3-diols in high yield and excellent stereochemical purity. The choice of benzoyl as N-protecting group is critical since the observed N- to O-Bz transfer during the process prevents later undesired isomerizations in the adducts and keeps all heteroatoms protected.
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http://dx.doi.org/10.1021/acs.joc.6b02765DOI Listing
February 2017

Accurate Assessment of the Oxygen Reduction Electrocatalytic Activity of Mn/Polypyrrole Nanocomposites Based on Rotating Disk Electrode Measurements, Complemented with Multitechnique Structural Characterizations.

J Anal Methods Chem 2016 30;2016:2030675. Epub 2016 Nov 30.

Dipartimento di Ingegneria dell'Innovazione, Università del Salento, Via Monteroni, 73100 Lecce, Italy.

This paper reports on the quantitative assessment of the oxygen reduction reaction (ORR) electrocatalytic activity of electrodeposited Mn/polypyrrole (PPy) nanocomposites for alkaline aqueous solutions, based on the Rotating Disk Electrode (RDE) method and accompanied by structural characterizations relevant to the establishment of structure-function relationships. The characterization of Mn/PPy films is addressed to the following: (i) morphology, as assessed by Field-Emission Scanning Electron Microscopy (FE-SEM) and Atomic Force Microscope (AFM); (ii) local electrical conductivity, as measured by Scanning Probe Microscopy (SPM); and (iii) molecular structure, accessed by Raman Spectroscopy; these data provide the background against which the electrocatalytic activity can be rationalised. For comparison, the properties of Mn/PPy are gauged against those of graphite, PPy, and polycrystalline-Pt (poly-Pt). Due to the literature lack of accepted protocols for precise catalytic activity measurement at poly-Pt electrode in alkaline solution using the RDE methodology, we have also worked on the obtainment of an intralaboratory benchmark by evidencing some of the time-consuming parameters which drastically affect the reliability and repeatability of the measurement.
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http://dx.doi.org/10.1155/2016/2030675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155125PMC
November 2016

IMPROV-ED study: outcomes after discharge for an episode of acute-decompensated heart failure and comparison between patients discharged from the emergency department and hospital wards.

Clin Res Cardiol 2017 May 22;106(5):369-378. Epub 2016 Dec 22.

Emergency Department, Home Hospitalization and Short Stay Unit, Hospital General de Alicante, Alicante, Spain.

Objective: To define the short- and mid-term outcomes of patients discharged after an episode of acute-decompensated heart failure (ADHF) and evaluate the differences between patients discharged directly from the emergency department (ED) and those discharged after hospitalization.

Methods: We performed a prospective, multicenter, cohort-designed study, including consecutive patients diagnosed with ADHF in 27 Spanish EDs. Thirty-four variables on epidemiology, comorbidity, baseline status, vital signs, signs of congestion, laboratory tests, and treatment were collected in every patient. The primary outcome was a combined endpoint of ED revisit (without hospitalization) or hospitalization due to ADHF, or all-cause death. Secondary outcomes were each of these three events individually. Outcomes were obtained by survival analysis at different timepoints in the entire cohort, and crude and adjusted comparisons were carried out between patients discharged directly from the ED and after hospitalization.

Results: Of the 3233 patients diagnosed with ADHF during a 2-month period, we analyzed 2986 patients discharged alive: 787 (26.4%) discharged from the ED and 2199 (73.6%) after hospitalization. The cumulative percentages of events for the whole cohort (at 7/30/180 days) for the combined endpoint were 7.8/24.7/57.8; for ED revisit 2.5/9.4/25.5; for hospitalization 4.6/15.3/40.7; and for death 0.9/4.3/16.8. After adjustment for patient profile and center, significant increases were found in the hazard ratios for ED- compared to hospital-discharged patients in the combined endpoint, ED revisit and hospitalization, being higher at short-term [at 7 days, 2.373 (1.678-3.355), 2.069 (1.188-3.602), and 3.071 (1.915-4.922), respectively] than at mid-term [at 180 days, 1.368 (1.160-1.614), 1.642 (1.265-2.132), and 1.302 (1.044-1.623), respectively]. No significant differences were found in death.

Conclusions: Patients with ADHF discharged from the ED have worse outcomes, especially at short term, than those discharged after hospitalization. The definition and implementation of effective strategies to improve patient selection for direct ED discharge are needed.
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http://dx.doi.org/10.1007/s00392-016-1065-yDOI Listing
May 2017

High quality RNA extraction from Maqui berry for its application in next-generation sequencing.

Springerplus 2016 3;5(1):1243. Epub 2016 Aug 3.

Laboratorio de Biotecnología Vegetal, Centro de Genómica y Bioinformática, Universidad Mayor, 8580000 Santiago, Chile.

Maqui berry (Aristotelia chilensis) is a native Chilean species that produces berries that are exceptionally rich in anthocyanins and natural antioxidants. These natural compounds provide an array of health benefits for humans, making them very desirable in a fruit. At the same time, these substances also interfere with nucleic acid preparations, making RNA extraction from Maqui berry a major challenge. Our group established a method for RNA extraction of Maqui berry with a high quality RNA (good purity, good integrity and higher yield). This procedure is based on the adapted CTAB method using high concentrations of PVP (4 %) and β-mercaptoethanol (4 %) and spermidine in the extraction buffer. These reagents help to remove contaminants such as polysaccharides, proteins, phenols and also prevent the oxidation of phenolic compounds. The high quality of RNA isolated through this method allowed its uses with success in molecular applications for this endemic Chilean fruit, such as differential expression analysis of RNA-Seq data using next generation sequencing (NGS). Furthermore, we consider that our method could potentially be used for other plant species with extremely high levels of antioxidants and anthocyanins.
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http://dx.doi.org/10.1186/s40064-016-2906-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970997PMC
August 2016

Deep sequencing reveals the complete genome and evidence for transcriptional activity of the first virus-like sequences identified in Aristotelia chilensis (Maqui Berry).

Viruses 2015 Apr 3;7(4):1685-99. Epub 2015 Apr 3.

Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Santiago 8580000, Chile.

Here, we report the genome sequence and evidence for transcriptional activity of a virus-like element in the native Chilean berry tree Aristotelia chilensis. We propose to name the endogenous sequence as Aristotelia chilensis Virus 1 (AcV1). High-throughput sequencing of the genome of this tree uncovered an endogenous viral element, with a size of 7122 bp, corresponding to the complete genome of AcV1. Its sequence contains three open reading frames (ORFs): ORFs 1 and 2 shares 66%-73% amino acid similarity with members of the Caulimoviridae virus family, especially the Petunia vein clearing virus (PVCV), Petuvirus genus. ORF1 encodes a movement protein (MP); ORF2 a Reverse Transcriptase (RT) and a Ribonuclease H (RNase H) domain; and ORF3 showed no amino acid sequence similarity with any other known virus proteins. Analogous to other known endogenous pararetrovirus sequences (EPRVs), AcV1 is integrated in the genome of Maqui Berry and showed low viral transcriptional activity, which was detected by deep sequencing technology (DNA and RNA-seq). Phylogenetic analysis of AcV1 and other pararetroviruses revealed a closer resemblance with Petuvirus. Overall, our data suggests that AcV1 could be a new member of Caulimoviridae family, genus Petuvirus, and the first evidence of this kind of virus in a fruit plant.
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http://dx.doi.org/10.3390/v7041685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411674PMC
April 2015

Draft Genome of Chilean Honeybee (Apis mellifera) Gut Strain Lactobacillus kunkeei MP2.

Genome Announc 2014 Oct 9;2(5). Epub 2014 Oct 9.

Centro de Genómica y Bioinformática (CGyB), Facultad de Ciencias, Universidad Mayor, Santiago, Chile

Here, we report the first draft genome sequence of Lactobacillus kunkeei strain MP2, isolated from a Chilean honeybee gut. The sequenced genome has a total size of 1.58 Mb distributed into 44 contigs and 1,356 protein-coding sequences.
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http://dx.doi.org/10.1128/genomeA.01013-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192385PMC
October 2014

Attenuation of early atherosclerotic lesions by immunotolerance with β2 glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a murine model.

J Vasc Surg 2015 Dec 17;62(6):1625-31. Epub 2014 Jul 17.

Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, Madrid, Spain.

Objective: This study assessed the effect of cellular and humoral autoimmune response inhibition after immunization with β2-glycoprotein I (β2-GPI) and the effect of immunomodulation with interleukin (IL)-2 and IL-10 in the development of early atherosclerotic vascular lesion in a murine model. Atherosclerosis is increasingly considered a chronic inflammatory disease with pathogenic autoimmune processes. Regulatory T cells, and their cytokines, have been implicated in the inhibition of the development of atherosclerotic lesions and involved in the immunologic tolerance induction.

Methods: Eight-week-old male C57BL6 LDL-receptor deficient (LDLR(-/-)) mice were fed a cholesterol-rich (2.8%), high-saturated-fat (82%) diet for a week and divided in five groups. The groups received the following intravenous immunizations: group I (control group): one dose of 5 μg β2-GPI; group II: 5 μg β2-GPI I and 1 μg IL-2; group III: 5 μg β2-GPI and 0.75 μg of IL-10; and group IV: 5 μg β2-GPI, 1 μg IL-2, and 0.75 μg IL-10. The aortas of the mice were assessed 8 weeks after inoculation to determine the aortic lesion size and composition in all groups.

Results: β2-GPI immunization attenuated the early atherosclerotic lesions development compared with the control group (P = .001). Macroscopic and histologic aortic atherosclerotic lesions were significantly decreased in the IL-2 and IL-10-treated groups in β2-GPI-tolerant mice compared with the β2-GPI-tolerant group without cytokine injection (P = .001). The association of both cytokines did not provoke a major inhibition in the atherosclerosis development when compared with groups injected with the two cytokines separately.

Conclusions: The immunotolerance induction against β2-GPI attenuates the development of atherosclerosis lesions in an animal model, enhanced by downregulation of the cellular and humoral autoimmune response provoked by IL-2 and IL-10.
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http://dx.doi.org/10.1016/j.jvs.2014.05.096DOI Listing
December 2015

Transient electrostatic interactions dominate the conformational equilibrium sampled by multidomain splicing factor U2AF65: a combined NMR and SAXS study.

J Am Chem Soc 2014 May 29;136(19):7068-76. Epub 2014 Apr 29.

University Grenoble Alpes, ‡CNRS, and §CEA, Protein Dynamics and Flexibility, Institut de Biologie Structurale , 38000 Grenoble, France.

Multidomain proteins containing intrinsically disordered linkers exhibit large-scale dynamic modes that play key roles in a multitude of molecular recognition and signaling processes. Here, we determine the conformational space sampled by the multidomain splicing factor U2AF65 using complementary nuclear magnetic resonance spectroscopy and small-angle scattering data. Available degrees of conformational freedom are initially stochastically sampled and experimental data then used to delineate the potential energy landscape in terms of statistical probability. The spatial distribution of U2AF65 conformations is found to be highly anisotropic, comprising significantly populated interdomain contacts that appear to be electrostatic in origin. This hypothesis is supported by the reduction of signature PREs reporting on expected interfaces with increasing salt concentration. The described spatial distribution reveals the complete spectrum of the unbound forms of U2AF65 that coexist with the small percentage of a preformed RNA-bound domain arrangement required for polypyrimidine-tract recognition by conformational selection. More generally, the proposed approach to describing conformational equilibria of multidomain proteins can be further combined with other experimental data that are sensitive to domain dynamics.
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http://dx.doi.org/10.1021/ja502030nDOI Listing
May 2014

The role of molecular structure of sugar-phosphate backbone and nucleic acid bases in the formation of single-stranded and double-stranded DNA structures.

Biopolymers 2014 Jun;101(6):640-50

Autonomous University of Puebla, Puebla, 72570, Mexico.

Our previous DFT computations of deoxydinucleoside monophosphate complexes with Na(+)-ions (dDMPs) have demonstrated that the main characteristics of Watson-Crick (WC) right-handed duplex families are predefined in the local energy minima of dDMPs. In this work, we study the mechanisms of contribution of chemically monotonous sugar-phosphate backbone and the bases into the double helix irregularity. Geometry optimization of sugar-phosphate backbone produces energy minima matching the WC DNA conformations. Studying the conformational variability of dDMPs in response to sequence permutation, we found that simple replacement of bases in the previously fully optimized dDMPs, e.g. by constructing Pyr-Pur from Pur-Pyr, and Pur-Pyr from Pyr-Pur sequences, while retaining the backbone geometry, automatically produces the mutual base position characteristic of the target sequence. Based on that, we infer that the directionality and the preferable regions of the sugar-phosphate torsions, combined with the difference of purines from pyrimidines in ring shape, determines the sequence dependence of the structure of WC DNA. No such sequence dependence exists in dDMPs corresponding to other DNA conformations (e.g., Z-family and Hoogsteen duplexes). Unlike other duplexes, WC helix is unique by its ability to match the local energy minima of the free single strand to the preferable conformations of the duplex.
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http://dx.doi.org/10.1002/bip.22432DOI Listing
June 2014

Latin-American Special Olympics athletes: evaluation of oral health status, 2010.

Spec Care Dentist 2013 Sep-Oct;33(5):209-12. Epub 2013 Mar 7.

University of Puerto Rico School of Dental Medicine, Puerto Rico.

Objectives: The purpose of this study was to evaluate the oral health status and dental needs of the athletes with intellectual disabilities from Latin-American and Caribbean countries who were participating in the II Latin-American Special Olympics games held in Puerto Rico, February 2010.

Methods: There were 930 athletes who participated in the games, of whom 445 received a dental examination, including 367 from Latin-American and 78 from Caribbean countries. Forty-four trained and standardized dental professionals performed dental screenings of athletes with intellectual disabilities, following Special Olympic Special Smiles and CDC protocols. These criteria were used to record untreated caries, missing and filled teeth, and gingival status. Socio-demographics, existence, and severity of pain and oral hygiene habits were assessed by questionnaire. Statistical analysis was performed using EPI-INFO and SPSS Statistical Program to produce descriptive statistics and chi-square test.

Results: Untreated dental caries was recorded for more than half of the examined athletes. Missing teeth were noted in more than one-third of the athletes. More than half of the participants had signs of gingival disease and half needed preventive mouth guards. Statistics for each Latin-American country suggests a dissimilar trend of dental decay and treatment needs among nations.

Conclusions: While the Special Olympic athletes may not be representative of the entire population of individuals with intellectual disabilities in their specific country, the general consistency of the oral health status of these athletes from the 31 countries supports the certainty of the need for increased dental services for individuals with intellectual disability in the respective countries.
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http://dx.doi.org/10.1111/scd.12019DOI Listing
September 2015

An orphan viral TNF receptor superfamily member identified in lymphocystis disease virus.

Virol J 2013 Jun 7;10:188. Epub 2013 Jun 7.

Centro de Biología Molecular ¨Severo Ochoa¨, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.

Background: Lymphocystis disease virus (LCDV) is a large icosahedral dsDNA-containing virus of the Lymphocystivirus genus within the Iridoviridae family that can cause disease in more than 140 marine and freshwater fish species. While several isolates have been charcaterized and classified into distinct genotypes the complete genomic sequence is currently only available from two species, the LCDV-1, isolated from flounder (Platichtys flesus) in Europe and the LCDV-C, isolated from Japanese cultured flounder (Paralichthys olivaceus) in China. Analysis of the genome of LCDV-C showed it to encode a protein named LDVICp016 with similarities to the Tumour necrosis factor receptor (TNFR) superfamily with immunomodulatory potential.

Findings: We have expressed and purified the recombinant protein LDVICp016 and screened for potential interaction partners using surface plasmon resonance. Commercially available human and mouse members of the TNF superfamily (TNFSF), along with a representative set of fish-derived TNFSF were tested.We have found the LDVICp016 protein to be secreted and we have identified a second viral TNFR encoded by ORF 095 of the same virus. None of the 42 tested proteins were found to interact with LDVICp016.

Conclusions: We show that LDVICp016 is a secreted protein belonging to the TNF receptor family that may be part of a larger gene family in Lymphocystiviruses. While the ligand of this protein remains unknown, possibly due to the species specific nature of this interaction, further investigations into the potential role of this protein in the blockade of immune responses in its fish host are required.
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http://dx.doi.org/10.1186/1743-422X-10-188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691878PMC
June 2013

Antioxidant effect of human adult adipose-derived stromal stem cells in alveolar epithelial cells undergoing stretch.

Respir Physiol Neurobiol 2013 Aug 30;188(1):1-8. Epub 2013 Apr 30.

Critical Care Department, Hospital Universitario de Getafe, Madrid, Spain.

Introduction: Alveolar epithelial cells undergo stretching during mechanical ventilation. Stretch can modify the oxidative balance in the alveolar epithelium. The aim of the present study was to evaluate the antioxidant role of human adult adipose tissue-derived stromal cells (hADSCs) when human alveolar epithelial cells were subjected to injurious cyclic overstretching.

Methods: A549 cells were subjected to biaxial stretch (0-15% change in surface area for 24h, 0.2Hz) with and without hADSCs. At the end of the experiments, oxidative stress was measured as superoxide generation using positive nuclear dihydroethidium (DHE) staining, superoxide dismutase (SOD) activity in cell lysates, 8-isoprostane concentrations in supernatant, and 3-nitrotyrosine by indirect immunofluorescence in fixed cells.

Results: Cyclically stretching of AECs induced a significant decrease in SOD activity, and an increase in 8-isoprostane concentrations, DHE staining and 3-nitrotyrosine staining compared with non-stretched cells. Treatment with hADSCs significantly attenuated stretch-induced changes in SOD activity, 8-isoprostane concentrations, DHE and 3-nitrotyrosine staining.

Conclusion: These data suggest that hADSCs have an anti-oxidative effect in human alveolar epithelial cells undergoing cyclic stretch.
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http://dx.doi.org/10.1016/j.resp.2013.04.007DOI Listing
August 2013

Total synthesis of (-)-isoavenaciolide.

J Org Chem 2013 Feb 31;78(4):1519-24. Epub 2013 Jan 31.

Departament de Química Orgànica and Institut de Biomedicina de la Universitat de Barcelona, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1, 08028-Barcelona, Spain.

An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1-undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2-thiophenecarboxaldehyde.
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http://dx.doi.org/10.1021/jo302598hDOI Listing
February 2013