Publications by authors named "Pilar Romero"

44 Publications

Replacing "Apparent Life Threatening Event" (ALTE) with "Brief Resolved Unexplained Event" (BRUE). A retrospective review of the ALTEs that meet the criteria of a BRUE.

An Pediatr (Engl Ed) 2020 Oct 22;93(4):261-262. Epub 2020 Sep 22.

Unidad de Lactantes y Pediatría General, Servicio de Pediatría, Hospital Doce de Octubre, Madrid, Spain.

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http://dx.doi.org/10.1016/j.anpede.2019.12.010DOI Listing
October 2020

Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg).

Am J Gastroenterol 2021 06;116(6):1220-1229

Gastroenterology Unit, Athens Medical Center, Paleo Faliron General Hospital Athens, Greece.

Introduction: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management."

Methods: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control.

Results: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies.

Discussion: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.
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http://dx.doi.org/10.14309/ajg.0000000000001246DOI Listing
June 2021

A comparison of the value of two machine learning predictive models to support bovine tuberculosis disease control in England.

Prev Vet Med 2021 Mar 15;188:105264. Epub 2021 Jan 15.

Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.

Nearly a decade into Defra's current eradication strategy, bovine tuberculosis (bTB) remains a serious animal health problem in England, with c.30,000 cattle slaughtered annually in the fight against this insidious disease. There is an urgent need to improve our understanding of bTB risk in order to enhance the current disease control policy. Machine learning approaches applied to big datasets offer a potential way to do this. Regularized regression and random forest machine learning methodologies were implemented using 2016 herd-level data to generate the best possible predictive models for a bTB incident in England and its three surveillance risk areas (High-risk area [HRA], Edge area [EA] and Low-risk area [LRA]). Their predictive performance was compared and the best models in each area were used to characterize herds according to risk. While all models provided excellent discrimination, random forest models achieved the highest balanced accuracy (i.e. average of sensitivity and specificity) in England, HRA and LRA, whereas the regularized regression LASSO model did so in the EA. The time since the last confirmed incident was resolved was the only variable in the top-ten ranking in all areas according to both types of models, which highlights the importance of bTB history as a predictor of a new incident. Risk categorisation based on Receiver Operating Characteristic (ROC) analysis was carried out using the best predictive models in each area setting a 99 % threshold value for sensitivity and specificity (97 % in the LRA). Thirteen percent of herds in the whole of England as well as in its HRA, 14 % in its EA and 31 % in its LRA were classified as high-risk. These could be selected for the deployment of additional disease control measures at national or area level. In this way, low-risk herds within the area considered would not be penalised unnecessarily by blanket control measures and limited resources be used more efficiently. The methodology presented in this paper demonstrates a way to accurately identify high-risk farms to inform a targeted disease control and prevention strategy in England that supplements existing population strategies.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105264DOI Listing
March 2021

Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg).

J Clin Gastroenterol 2021 Jan 5;Publish Ahead of Print. Epub 2021 Jan 5.

Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Digestive Service, HM Sanchinarro, Madrid Digestive Unit, Agencia Sanitaria Costa del Sol, Marbella, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Málaga Digestive Unit, Hospital de Valme, Sevilla Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Universidad del País Vasco (UPV/EHU), Donostia Hospital de Tomelloso, Ciudad Real, Tomelloso Gastroenterology Unit, Hospital Universitario Central de Asturias, Oviedo Hospital General Universitario de Valencia, Valencia Hospital San Pedro de Alcántara, Cáceres Hospital Río Hortega Hospital Clínico Universitario, Valladolid, Spain Department of Surgical and Clinical Sciences, University of Bologna, Bologna Gastronterology Area, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy Gastroenterology Unit, AM DC Rogaska, Rogaska Slatina DC Bled Slovenj Gradec General Hospital, Slovenj Gradec, Slovenia Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania Department of Pancreatobiliary and Upper GI Diseases, Moscow Clinical Scientific Center, and A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow Gastrocentre Perm, Perm Kazan State Medical University, Kazan, Russia Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux Cedex, France Trinity College Dublin, Faculty of Health Sciences, Trinity College Dublin, Dublin/IE, Faculty of Health Sciences, Dublin, Ireland.

Background: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors.

Aim: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management".

Methods: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice.

Results: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines.

Conclusion: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.
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http://dx.doi.org/10.1097/MCG.0000000000001482DOI Listing
January 2021

On-POM Ring-Opening Polymerisation of N-Carboxyanhydrides.

Angew Chem Int Ed Engl 2021 02 19;60(7):3449-3453. Epub 2021 Jan 19.

Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, c/ Pedro Cerbuna 12, 50009, Zaragoza, Spain.

The ring-opening polymerisation of α-amino acid N-carboxyanhydrides (NCAs) offers a simple and scalable route to polypeptides with predicted and narrow molecular weight distributions. Here we show how polyoxometalates (POMs)-redox-active molecular metal-oxide anions-can serve as inorganic scaffold initiators for such NCA polymerisations. This "On-POM polymerisation" strategy serves as an innovative platform to design hybrid materials with additive or synergistic properties stemming from the inorganic and polypeptide component parts. We have used this synthetic approach to synthesise a library of bactericidal poly(lysine)-POM hybrid derivatives that can be used to prevent biofilm formation. This versatile "On-POM polymerisation" method provides a flexible synthetic approach for combining inorganic scaffolds with amino acids, and the potential to tailor and improve the specificity and performance of hybrid antimicrobial materials.
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http://dx.doi.org/10.1002/anie.202013563DOI Listing
February 2021

Micellar Nanocarriers from Dendritic Macromolecules Containing Fluorescent Coumarin Moieties.

Polymers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

Departamento de Química Orgánica, Instituto de Nanociencia y Materiales de Aragón (INMA), Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.

The design of efficient drug-delivery vehicles remains a big challenge in materials science. Herein, we describe a novel class of amphiphilic hybrid dendrimers that consist of a poly(amidoamine) (PAMAM) dendritic core functionalized with MPA dendrons bearing cholesterol and coumarin moieties. Their self-assembly behavior both in bulk and in water was investigated. All dendrimers exhibited smectic A or hexagonal columnar liquid crystal organizations, depending on the generation of the dendrimer. In water, these dendrimers self-assembled to form stable spherical micelles that could encapsulate Nile Red, a hydrophobic model compound. The cell viability in vitro of the micelles was studied in HeLa cell line, and proved to be non-toxic up to 72 h of incubation. Therefore, these spherical micelles allow the encapsulation of hydrophobic molecules, and at the same time provided fluorescent traceability due to the presence of coumarin units in their chemical structure, demonstrating the potential of these dendrimers as nanocarriers for drug-delivery applications.
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http://dx.doi.org/10.3390/polym12122872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761282PMC
November 2020

Repurposing Heparin as Antimalarial: Evaluation of Multiple Modifications Toward In Vivo Application.

Pharmaceutics 2020 Aug 29;12(9). Epub 2020 Aug 29.

Barcelona Institute for Global Health (ISGlobal, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain.

Heparin is a promising antimalarial drug due to its activity in inhibiting invasion of red blood cells and to the lack of resistance evolution by the parasite against it, but its potent anticoagulant activity is preventing the advance of heparin along the clinical pipeline. We have determined, in in vitro cultures, the antimalarial activity of heparin-derived structures of different origins and sizes, to obtain formulations having a good balance of in vitro safety (neither cytotoxic nor hemolytic), low anticoagulant activity (≤23 IU/mL according to activated partial thromboplastin time assays), and not too low antimalarial activity (IC50 at least around 100 µg/mL). This led to the selection of five chemically modified heparins according to the parameters explored, i.e., chain length, sulfation degree and position, and glycol-split, and whose in vivo toxicity indicated their safety for mice up to an intravenous dose of 320 mg/kg. The in vivo antimalarial activity of the selected formulations was poor as a consequence of their short blood half-life. The covalent crosslinking of heparin onto the surface of polyethylene glycol-containing liposomes did not affect its antimalarial activity in vitro and provided higher initial plasma concentrations, although it did not increase mean circulation time. Finding a suitable nanocarrier to impart long blood residence times to the modified heparins described here will be the next step toward new heparin-based antimalarial strategies.
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http://dx.doi.org/10.3390/pharmaceutics12090825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557421PMC
August 2020

Coumarin-Containing Pillar[5]arenes as Multifunctional Liquid Crystal Macrocycles.

J Org Chem 2020 Jul 1;85(14):8944-8951. Epub 2020 Jul 1.

Departamento de Quı́mica Orgánica, Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain.

Liquid crystal macrocycles (LCMs) combine the unique properties of liquid crystals with those associated with macrocyclic compounds-shape persistence and the capability of hosting small molecules. Herein, we investigate the grafting of coumarin-containing promesogenic moieties to pillar[5]arene as a strategy to obtain multifunctional LCMs. Pillar[5]arenes containing 10 and 30 coumarin units are glassy materials with nematic mesomorphism. Moreover, the coumarin moieties afford the pillar[5]arene derivatives with enhanced film-forming and photoresponsive properties. Photodimerization of the coumarin moieties results in cross-linked polymer networks, which can be used as alignment layers. Therefore, liquid-crystal coumarin-containing pillar[5]arenes represent a significant addition to the family of LCMs and may become useful for the development of engineered, hierarchical structures and materials.
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http://dx.doi.org/10.1021/acs.joc.0c00852DOI Listing
July 2020

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

Helicobacter 2020 Jun 16;25(3):e12686. Epub 2020 Mar 16.

Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel.

Background: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended.

Aim: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg).

Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019.

Results: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases.

Conclusion: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.
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http://dx.doi.org/10.1111/hel.12686DOI Listing
June 2020

Decision tree machine learning applied to bovine tuberculosis risk factors to aid disease control decision making.

Prev Vet Med 2020 Feb 30;175:104860. Epub 2019 Nov 30.

Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.

Identifying and understanding the risk factors for endemic bovine tuberculosis (TB) in cattle herds is critical for the control of this disease. Exploratory machine learning techniques can uncover complex non-linear relationships and interactions within disease causation webs, and enhance our knowledge of TB risk factors and how they are interrelated. Classification tree analysis was used to reveal associations between predictors of TB in England and each of the three surveillance risk areas (High Risk, Edge, and Low Risk) in 2016, identifying the highest risk herds. The main classifying predictor for farms in England overall related to the TB prevalence in the 100 nearest cattle herds. In the High Risk and Edge areas it was the number of slaughterhouse destinations and in the Low Risk area it was the number of cattle tested in surveillance tests. How long ago the last confirmed incident was resolved was the most frequent classifier in trees; if within two years, leading to the highest risk group of herds in the High Risk and Low Risk areas. At least two different slaughterhouse destinations led to the highest risk group of herds in England, whereas in the Edge area it was a combination of no contiguous low-risk neighbours (i.e. in a 1 km radius) and a minimum proportion of 6-23 month-old cattle in November. A threshold value of prevalence in 100 nearest neighbours increased the risk in all areas, although the value was specific to each area. Having low-risk contiguous neighbours reduced the risk in the Edge and High Risk areas, whereas high-risk ones increased the risk in England overall and in the Edge area specifically. The best classification tree models informed multivariable binomial logistic regression models in each area, adding statistical inference outputs. These two approaches showed similar predictive performance although there were some disparities regarding what constituted high-risk predictors. Decision tree machine learning approaches can identify risk factors from webs of causation: information which may then be used to inform decision making for disease control purposes.
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http://dx.doi.org/10.1016/j.prevetmed.2019.104860DOI Listing
February 2020

Impact of operational factors on HPV positivity rates in an HPV-based screening study in Colombia.

Int J Gynaecol Obstet 2018 Oct 16;143(1):44-51. Epub 2018 Jul 16.

Prevention and Implementation Group, Early Detection and Prevention Section, International Agency for Research on Cancer (IARC), Lyon, France.

Objective: To assess the effect of operational factors on the positivity rates of three HPV assays.

Methods: Within the cross-sectional ESTAMPA study, women aged 30-64 years were recruited at healthcare centers from Soacha, Colombia, during 2012-2015. Cervical samples were collected for cotesting with Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD, USA), and either Aptima (Hologic, Marlborough, MA, USA) or Cobas 4800 (Roche Diagnostics, Indianapolis, IN, USA). The effect of operational factors on assay performance was assessed using adjusted positivity rates obtained from logistic regression models.

Results: There were 4168 women included. For samples collected in assay-specific medium, positivity rate differences were associated with the expertise of the nurse collecting the sample (P=0.014 HC2; P=0.091 Aptima) and if sample collection occurred after an initial cytology (P=0.025 HC2; P=0.033 Aptima). If PreservCyt medium (Hologic) was used, HC2 positivity differences were observed depending on the time between sample collection and processing (P=0.026) and on the laboratory technician processing the samples (P=0.003). No differences were observed for PreservCyt samples processed with Aptima or Cobas.

Conclusion: Nurse expertise, collection of previous cytology, processing time, and laboratory technician could influence HPV assay performance. Suitable quality assurance protocols for HPV-based screening programs are required. ClinicalTrials.gov: NCT01881659.
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http://dx.doi.org/10.1002/ijgo.12574DOI Listing
October 2018

Cationic poly(ester amide) dendrimers: alluring materials for biomedical applications.

J Mater Chem B 2018 Jun 31;6(23):3956-3968. Epub 2018 May 31.

Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, Spain.

Novel cationic poly(ester amide) dendrimers have been synthesized by copper(i) azide-alkyne cycloaddition (CuAAC) of a tripropargylamine core and azide-terminated dendrons, in turn prepared by iterative amide coupling of the new monomer 2,2'-bis(glycyloxymethyl)propionic acid (bis-GMPA). The alternation of ester and amide groups provided a dendritic scaffold that was totally biocompatible and degradable in aqueous media at physiological and acidic pH. The tripodal dendrimers naturally formed rounded aggregates with a drug that exhibited low water solubility, camptothecin, thus improving its cell viability and anti-Hepatitis C virus (anti-HCV) activity. The presence of numerous peripheral cationic groups enabled these dendrimers to form dendriplexes with both pDNA and siRNA and they showed effective in vitro siRNA transfection in tumoral and non-tumoral cell lines.
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http://dx.doi.org/10.1039/c8tb00639cDOI Listing
June 2018

Francisella philomiragia: Think of Chronic Granulomatous Disease.

J Clin Immunol 2018 04 16;38(3):257-259. Epub 2018 Apr 16.

Internal Medicine Department, La Paz Universitary Hospital, Madrid, Spain.

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http://dx.doi.org/10.1007/s10875-018-0498-7DOI Listing
April 2018

Not Only Columns: High Hole Mobility in a Discotic Nematic Mesophase Formed by Metal-Containing Porphyrin-Core Dendrimers.

Angew Chem Int Ed Engl 2017 01 28;56(5):1259-1263. Epub 2016 Dec 28.

LASCAMM CR-INSTM, CNR-NANOTEC SS di Rende, Dipartimento di Fisica, Università della Calabria, 87036, Rende, Italy.

We report a new family of multifunctional liquid-crystalline porphyrin-core dendrimers that have coumarin functional groups around the porphyrin core. Porphyrin metalation strongly affects the photophysical properties, and therefore Zn and Cu derivatives have also been prepared. All the synthesized dendrimers form a nematic discotic mesophase. Their high tendency for homeotropic alignment makes these dendrimers excellent candidates for device applications, owing to their easy processability, spontaneous alignment between electrodes, and self-healing of defects because of their dynamic nature. The charge mobility values of these materials are the highest ever reported for a nematic discotic phase. Moreover, these values are similar to the highest values reported for ordered columnar mesophases, and this shows that a supramolecular organization in columns is not necessary to achieve high charge mobility.
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http://dx.doi.org/10.1002/anie.201611017DOI Listing
January 2017

Lack of Accuracy of Biomarkers and Physical Examination to Detect Bacterial Infection in Febrile Infants.

Pediatr Emerg Care 2016 Oct;32(10):664-668

From the Pediatrics Department, 12 de Octubre University Hospital, Madrid, Spain.

Objectives: The aim of this study was to analyze the usefulness of physical examination, C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and absolute neutrophils counts (ANCs) for the diagnosis of invasive bacterial infections (IBIs) and potentially serious bacterial infections in infants younger than the age of 3 months presenting with fever without source (FWS) to the emergency department (ED).

Methods: A descriptive retrospective study that includes all infants aged younger than 3 months who presented with FWS to the ED between July 2008 and January 2012. We evaluated diagnostic performance for each test by receiver operating characteristic curve analysis. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were also calculated.

Results: Three hundred eighteen patients met the inclusion criteria. Eleven bacteremia (3.5%) and 76 urinary tract infections (23.9%) were diagnosed. To detect IBI, the areas under the curve for the different tests were as follows: PCT, 0.77 (95% confidence interval [CI], 0.57-0.96); CRP, 0.54 (95% CI, 0.36-0.73); ANC, 0.53 (95% CI, 0.34-0.71); and WBC, 0.42 (0.24-0.61). To detect potentially serious bacterial infections, the areas under the curve were as follows: PCT, 0.66 (95% CI, 0.59-0.74); CRP, 0.68 (0.60-0.76); ANC, 0.64 (0.56-0.71); and WBC, 0.66 (0.58-0.72).

Conclusions: Procalcitonin is better than CRP, WBC, and ANC to confirm or dismiss the presence of an IBI in infants aged younger than 3 months presenting with FWS to the ED. However, it could not identify almost 30% of infants with IBI. Most patients diagnosed with IBI (10 of 11) presented abnormal values in at least one of the analytical parameters and/or physical appearance. Four of 5 patients with IBI and well appearing presented abnormal results in at least one of the analytical parameters. Therefore, the development of tools combining different tests including the new biomarkers could increase the reliability of the tests for the diagnosis of IBI in these patients.
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http://dx.doi.org/10.1097/PEC.0000000000000401DOI Listing
October 2016

H-Bonded Donor-Acceptor Units Segregated in Coaxial Columnar Assemblies: Toward High Mobility Ambipolar Organic Semiconductors.

J Am Chem Soc 2016 09 14;138(38):12511-8. Epub 2016 Sep 14.

Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón (ICMA), Facultad de Ciencias, Universidad de Zaragoza-CSIC , 50009 Zaragoza, Spain.

A novel approach to ambipolar semiconductors based on hydrogen-bonded complexes between a star-shaped tris(triazolyl)triazine and triphenylene-containing benzoic acids is described. The formation of 1:3 supramolecular complexes was evidenced by different techniques. Mesogenic driving forces played a decisive role in the formation of the hydrogen-bonded complexes in the bulk. All of the complexes formed by nonmesogenic components gave rise to hexagonal columnar (Colh) liquid crystal phases, which are stable at room temperature. In all cases, X-ray diffraction experiments supported by electron density distribution maps confirmed triphenylene/tris(triazolyl)triazine segregation into hexagonal sublattices and lattices, respectively, as well as remarkable intracolumnar order. These highly ordered nanostructures, obtained by the combined supramolecular H-bond/columnar liquid crystal approach, yielded donor/acceptor coaxial organization that is promising for the formation of ambipolar organic semiconductors with high mobilities, as indicated by charge transport measurements.
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http://dx.doi.org/10.1021/jacs.6b06792DOI Listing
September 2016

Asistole after electroconvusise therapy.

Rev Psiquiatr Salud Ment 2017 Jan - Mar;10(1):61-62. Epub 2016 Mar 31.

Servicio de Anestesia y Reanimación, Hospital Galdakao, Usansolo, Bizkaia, España.

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http://dx.doi.org/10.1016/j.rpsm.2016.03.001DOI Listing
January 2018

Supramolecular columnar liquid crystals formed by hydrogen bonding between a clicked star-shaped s-triazine and benzoic acids.

Chemistry 2015 Jun 11;21(24):8859-66. Epub 2015 May 11.

Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, 50009 Zaragoza (Spain).

A star-shaped tris(triazolyl)triazine is shown to establish hydrogen-bond interactions with polycatenar benzoic acids. The formation of hydrogen-bonded triazine/acid complexes has been demonstrated both in solution and in bulk by different techniques. The complexes, mainly formed by nonmesogenic components, all show enantiotropic hexagonal columnar mesomorphism, which relies on the formation of hydrogen-bond complexes in a triazine/acid ratio of 1:3. This approach combines the straightforward synthesis of a nonmesomorphic triazine core by click chemistry, and the preparation of a supramolecular complex, providing a much more convenient route than covalent synthesis to modify the periphery of triazine discotics and thus to modulate their functionality.
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http://dx.doi.org/10.1002/chem.201500477DOI Listing
June 2015

Multifunctional supramolecular dendrimers with an s-triazine ring as the central core: liquid crystalline, fluorescence and photoconductive properties.

Chemistry 2014 Aug 17;20(32):10027-37. Epub 2014 Jun 17.

Departamento de Química Orgánica, Facultad de Ciencias-Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, 50009 Zaragoza (Spain).

Novel liquid crystal (LC) dendrimers have been synthesised by hydrogen bonding between an s-triazine as the central core and three peripheral dendrons derived from bis(hydroxymethyl)propionic acid. Symmetric acid dendrons bearing achiral promesogenic units have been synthesised to obtain 3:1 complexes with triazine that exhibit LC properties. Asymmetric dendrons that combine the achiral promesogenic unit and an active moiety derived from coumarin or pyrene structures have been synthesised in order to obtain dendrimers with photophysical and electrochemical properties. The formation of the complexes was confirmed by IR and NMR spectroscopy data. The liquid crystalline properties were investigated by differential scanning calorimetry, polarising optical microscopy and X-ray diffractometry. All complexes displayed mesogenic properties, which were smectic in the case of symmetric dendrons and their complexes and nematic in the case of asymmetric dendrons and their dendrimers. A supramolecular model for the lamellar mesophase, based mainly on X-ray diffraction studies, is proposed. The electrochemical behaviour of dendritic complexes was investigated by cyclic voltammetry. The UV/Vis absorption and emission properties of the compounds and the photoconductive properties of the dendrons and dendrimers were also investigated.
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http://dx.doi.org/10.1002/chem.201402646DOI Listing
August 2014

NMR spectroscopic study of the self-aggregation of 3-hexen-1,5-diyne derivatives.

Chemistry 2013 Jul 20;19(31):10271-9. Epub 2013 Jun 20.

Instituto de Nanociencia de Aragón, Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain.

The self-assembly of polycatenar molecules derived from 1,6-diphenyl-3,4-dipropyl-3-hexen-1,5-diyne has been studied in detail by solution NMR spectroscopy. The analysis of the concentration- and temperature-dependent evolution of the chemical shifts and the diffusion coefficients in [D12]cyclohexane agrees well with an isodesmic model of association in this solvent. The association constants for the stacking and entropy and enthalpy of the process have been obtained. The driving force for the aggregation process is provided by a negative enthalpy (ΔH), which is partially compensated by a negative entropy (ΔS). A structural study of the self-assembly in solution has been carried out with the help of NOESY NMR spectroscopic experiments.
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http://dx.doi.org/10.1002/chem.201204604DOI Listing
July 2013

Solid-state and solution structure of a hypervalent AX5 compound: Sb(C6F5)5.

Angew Chem Int Ed Engl 2012 Mar 3;51(11):2754-7. Epub 2012 Feb 3.

Instituto de Síntesis Química y Catálisis Homogénea, Universidad de Zaragoza-C.S.I.C., Spain.

Eliminating restraints: a trigonal-bipyramidal structure has been found to be the energetically favored geometry of the hypervalent AX(5) molecule Sb(C(6)F(5))(5) in the solid state and also in fluid solution, where molecules move freely and no crystal packing effects operate.
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http://dx.doi.org/10.1002/anie.201108858DOI Listing
March 2012

[Persistent polyclonal B-cell lymphocytosis: study of 35 cases].

Med Clin (Barc) 2011 May 10;136(13):565-73. Epub 2011 Mar 10.

Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, España.

Background And Objectives: Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity, presenting especially in adult smoker women. It is characterized by an increase of serum IgM, DR7-HLA haplotype, cytogenetic abnormalities and multiple IgH/BCL-2 rearrangements. To date, it has not been elucidated whether this is a benign or premalignant disorder. We analyzed the PPBL characteristics with especial attention to its evolution.

Patients And Methods: Thirty-five PPBL patients from 5 hospitals in Catalonia were retrospectively analyzed. A simultaneous morphologic review of the blood smears was performed by members of the GCCH in a 16 multiple-observer optic microscope. Clinical and biological data were also analyzed.

Results: PPBL presents in the majority of cases with persistent polyclonal B-cell lymphocytosis and affects primarily smoker women. The morphologic hallmark, in absence of viral infections, is the presence of activated lymphocytes with bilobulated and/or cleaved nuclei, and nuclear pockets in the ultrastructural study. Increased serum IgM, HLA-DR7 haplotype, chromosomal abnormalities such as i(3)(q10) and multiple IgH/BCL-2 rearrangements were detected. Thirty-four out of 35 patients are alive after a median follow up of 70.7 months. One patient died because of lung adenocarcinoma and another developed a follicular lymphoma without relation to PPBL.

Conclusions: PPBL has an asymptomatic and stable evolution, although it frequently presents genetic abnormalities. It remains unknown whether it is a premalignant entity, similar to monoclonal gammopathies of unknown significance. Hence, accurate cytologic diagnosis and follow-up are essential.
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http://dx.doi.org/10.1016/j.medcli.2010.09.048DOI Listing
May 2011

Clonal spread of levofloxacin-resistant streptococcus pneumoniae invasive isolates in Madrid, Spain, 2007 to 2009.

Antimicrob Agents Chemother 2011 May 7;55(5):2469-71. Epub 2011 Mar 7.

Departamento de Microbiología Clínica, Hospital Clínico San Carlos., Plaza de Cristo Rey s/n, 28040 Madrid, Spain.

Among 1,349 Streptococcus pneumoniae invasive isolates, 45 (3.3%) were levofloxacin resistant. Serotype distribution was as follows: 8 (n=32 isolates), 19A (n=4 isolates), 7F (n=3 isolates), 9V (n=2 isolates), 10A (n=1 isolate), 19F (n=1 isolate), 6B (n=1 isolate), and nontypeable (n=1 isolate). Levofloxacin-resistant isolates had dual mutations in the gyrA and parC genes. Serotype 8 strains corresponded to a capsular switching of the Sweden(15A)-25 clone. Levofloxacin resistance was also detected among multiresistant (ST276(19A), Spain9V-ST156, ST88(19F), and ST1542(6B)) and among usually antibiotic-susceptible (Netherlands7F-ST191, ST1201(19A), and ST2639(10A)) clones.
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http://dx.doi.org/10.1128/AAC.01380-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088247PMC
May 2011

Characterization of gliadin-specific Th17 cells from the mucosa of celiac disease patients.

Am J Gastroenterol 2011 Mar 4;106(3):528-38. Epub 2011 Jan 4.

Unidad de Inmunología, Facultad de Medicina, Universidad de Córdoba, Córdoba, Spain.

Objectives: Celiac disease (CD) is a disorder characterized by a deregulated immune response to ingested wheat gluten and related cereal proteins in susceptible individuals. It has been considered that the onset of CD is mediated by a skewed Th1 response. However, the participation of Th17 cells in the pathogenesis of the disease, a key cell population in other autoimmune disorders, has not been studied in detail. We have investigated the presence of Th17 cells in the mucosa of active CD patients and their functional implications in the pathogenesis of the disease.

Methods: T cells obtained from duodenum biopsies from 15 untreated patients and 11 control individuals were characterized by flow cytometry, immunoassays, and real-time PCR.

Results: We found gliadin-specific CD4(+) interleukin (IL)-17A-producing T cells in the mucosa of CD patients with a phenotype consisting of TCR (T-cell receptor)αβ(+) CD45RO(+) CD161(+) CCR6(+) (C-C chemokine receptor type 6) and IL-23R(+). Functional analysis showed that Th17 cells from CD patients are different from those of control individuals in terms of cytokines production. Th17 cells from CD patients, but not from controls, simultaneously express transforming growth factor-β (TGFβ). Th17 CD cells also produce interferon-γ (IFNγ), IL-21, and IL-22. The analysis of the transcription factors revealed a high expression of interferon regulatory factor-4 as a feature of gliadin-specific cells from CD patients with respect to controls.

Conclusions: Gliadin-specific Th17 cells are present in the mucosa of CD patients having a dual role in the pathogenesis of the disease as they produce proinflammatory cytokines (such as IL-17, IFNγ, IL-21), mucosa-protective IL-22, and regulatory TGFβ, which actively modulates IL-17A production by T cells in the celiac mucosa.
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http://dx.doi.org/10.1038/ajg.2010.465DOI Listing
March 2011

Synthesis, dynamic behavior, and reactivity of new unsaturated heterotrinuclear 46 valence electron complexes.

Inorg Chem 2011 Jan 8;50(1):285-98. Epub 2010 Dec 8.

Departamento de Química Inorgánica and Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza, CSIC, 50009 Zaragoza, Spain.

The reaction of [NBu(4)](2)[(C(6)F(5))(2)Pt(μ-PPh(2))(2)Pd(μ-PPh(2))(2)Pt(C(6)F(5))(2)] (1a) with [AgPPh(3)](+) results in the oxidation of two bridging diphenylphosphanides to give the 46e species [(PPh(3))(C(6)F(5))(2)Pt(2)(μ-P(2)Ph(2))Pd(μ-PPh(2))(μ-Ph(2)P(4)-P(3)Ph(2))Pt(1)(C(6)F(5))(2)] (3). Complex 3 displays two tetracoordinated terminal platinum centers and a central Pd atom that is bonded to three P atoms and that completes its coordination sphere by a rather long (3.237 Å) dative Pt(2) → Pd bond. Complex 3 is also obtained when [(R(F))(2)Pt(μ-PPh(2))Pd(μ-PPh(2))(μ-Ph(2)P-PPh(2))Pt(R(F))(2)] (2) is reacted with PPh(3). Analogously, the addition of PPh(2)Et, CO or pyridine to 2 affords the 46e complexes of general formula [(L)(C(6)F(5))(2)Pt(2)(μ-P(2)Ph(2))Pd(μ-PPh(2))(μ-Ph(2)P(4)-P(3)Ph(2))Pt(1)(C(6)F(5))(2)] (L = PPh(2)Et, 4; L = CO, 6; L = pyridine, 7). The geometry around Pt(2) is determined by the bulkiness of L bonded to Pt. Thus, in complexes 3 (L = PPh(3)) and 4 (L = PPh(2)Et), the ligand L occupies the trans position with respect to μ-P(2), and in 6 (L = CO), the ligand L occupies the cis position with respect to μ-P(2). Interestingly, for 7 (L = py), both isomers 7-trans and 7-cis, could be isolated. Although 4 did not react with an excess of PPh(2)Et, the reaction with the less sterically demanding CH(3)CN ligand resulted in the opening of the Pt(2)-P(2)-Pd cycle with formation of the saturated 48e species [(PPh(2)Et)(C(6)F(5))(2)Pt(μ-PPh(2))Pd(MeCN)(μ-PPh(2))(μ-Ph(2)P-PPh(2))Pt(C(6)F(5))(2)] (8). The saturated 48e complex [(CO)(C(6)F(5))(2)Pt(μ-PPh(2))Pd(MeCN)(μ-PPh(2))(μ-Ph(2)P-PPh(2))Pt(C(6)F(5))(2)] (9) was obtained by acetonitrile addition to 6. Beside the hindered rotation of the pentafluorophenyl groups and a flip-flop motion of the Pd-P-Pt(1)-P-P ring observed at low T, a rotation about the Pt(2)-P(2) bond and a P-C oxidative addition/reductive elimination process occur for 3 and 4 at room temperature. A "through-space" (19)F-(31)P spin-spin coupling between an ortho-F and the P(4) is observed for complexes 3 and 4, having the C(6)F(5) groups bonded to Pt(2) in mutually trans position. The XRD structures of complexes 3, 6, 7-trans, 7-cis, 8, and 9 are described.
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http://dx.doi.org/10.1021/ic101934tDOI Listing
January 2011

Prevention of in vitro hepatic stellate cells activation by the adenosine derivative compound IFC305.

Biochem Pharmacol 2010 Dec 9;80(11):1690-9. Epub 2010 Sep 9.

Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México 04510, D.F., Apdo. postal 70-243, Mexico.

We have previously shown that adenosine and the aspartate salt of adenosine (IFC305) reverse pre-established CCl(4)-induced cirrhosis in rats. However, their molecular mechanism of action is not clearly understood. Hepatic stellate cells (HSC) play a pivotal role in liver fibrogenesis leading to cirrhosis, mainly through their activation, changing from a quiescent adipogenic state to a proliferative myofibrogenic condition. Therefore, we decided to investigate the effect of IFC305 on primary cultured rat HSC. Our results reveal that this compound suppressed the activation of HSC, as demonstrated by the maintenance of a quiescent cell morphology, including lipid droplets content, inhibition of α-smooth muscle actin (α-SMA) and collagen α1(I) expression, and up-regulation of MMP-13, Smad7, and PPARγ expression, three key antifibrogenic genes. Furthermore, IFC305 was able to repress the platelet-derived growth factor (PDGF)-induced proliferation of HSC. This inhibition was independent of adenosine receptors stimulation; instead, IFC305 was incorporated into cells by adenosine transporters and converted to AMP by adenosine kinase. On the other hand, addition of pyrimidine ribonucleoside as uridine reversed the suppressive effect of IFC305 on the proliferation and activation of HSC, suggesting that intracellular pyrimidine starvation would be involved in the molecular mechanism of action of IFC305. In conclusion, IFC305 inhibits HSC activation and maintains their quiescence in vitro; these results could explain in part the antifibrotic liver beneficial effect previously described for this compound on the animal model.
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http://dx.doi.org/10.1016/j.bcp.2010.08.017DOI Listing
December 2010

Orthogonal action of noncovalent interactions for photoresponsive chiral columnar assemblies.

Angew Chem Int Ed Engl 2010 Jul;49(29):4910-4

Instituto de Ciencia de Materiales de Aragón, Química Orgánica, Facultad de Ciencias, Universidad de Zaragoza-C.S.I.C. 50009 Zaragoza, Spain.

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http://dx.doi.org/10.1002/anie.201000580DOI Listing
July 2010

[Gly482Ser polymorphism of the coactivator-1alpha of the activated receptor of peroxisome gamma proliferation in individuals from Maracaibo, Venezuela].

Invest Clin 2009 Sep;50(3):285-94

Cátedra de Bioquímica Clínica, Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.

The aim of this study was to determine the association of the Gly482Ser polymorphism of the PGC-1 gene with insulin resistance and type 2 diabetes mellitus in subjects from the city of Maracaibo. The study was performed on 64 no-diabetic subjects (36 without insulin resistance and 28 with insulin resistance) and 13 with type 2 diabetes. A clinical and nutritional history was carried out and the evaluation of anthropometric parameters was included. Fasting serum glucose, fasting serum insulin, total cholesterol, HDL-C and LDL-C, were measured. The Gly482Ser polymorphism was detected by PCR-RFLP. It was found that the allelic frequencies for A and G were 0.36 and 0.64, respectively. The population was found in genetic equilibrium of Hardy Weinberg. The genotypes of the polymorphism Gly482Ser were not associated with insulin resistance and type 2 diabetes mellitus (OR = 1.320, p = 0.74; OR = 2, p = 0.47 respectively). Nevertheless, the diabetic subjects with the genotype AA presented values of LDL-C higher (p < 0.05) than the individuals with the genotypes GG and GA. The diabetics with the genotype GA showed significantly higher concentrations of triglycerides (>150 mg/dL) compared with the genotype GG. According to the results, the polymorphism Gly482Ser of the PGC-1 gene would be able to contribute to the cardiovascular risk in type 2 diabetics, while in the insulin resistant individuals, this polymorphism was not associated with cardiovascular risk factors.
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September 2009
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