Publications by authors named "Ignacio Hernandez"

48 Publications

Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: Data from a Real-World Study in Spain.

Diabetes Ther 2021 May 16;12(5):1535-1551. Epub 2021 Apr 16.

Lilly Spain, Avenida de la Industria 30, Alcobendas, Madrid, Spain.

Introduction: This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain.

Methods: This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan-Meier curves. All analyses were descriptive.

Results: A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8-63.4) for dulaglutide, 45.7% (95% CI 41.0-50.4) for exenatide-QW and 46.6% (95% CI 42.1-51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was - 0.68% for patients who initiated dulaglutide, - 0.54% for patients who initiated exenatide-QW and - 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide.

Conclusion: Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide.
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http://dx.doi.org/10.1007/s13300-021-01039-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099971PMC
May 2021

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Hospital Ramón y Cajal Research Unit (IRYCIS), Cardiology Department, Universidad Francisco de Vitoria, 28223 Madrid, Spain.

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.
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http://dx.doi.org/10.3390/ijms22062902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001911PMC
March 2021

The Role of the SARS-CoV-2 S-Protein Glycosylation in the Interaction of SARS-CoV-2/ACE2 and Immunological Responses.

Viral Immunol 2021 04 19;34(3):165-173. Epub 2021 Feb 19.

Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

The current pandemic is caused by the coronavirus disease 2019 (COVID-19), which is, in turn, induced by a novel coronavirus (SARS-CoV-2) that triggers an acute respiratory disease. In recent years, the emergence of SARS-CoV-2 is the third highly pathogenic event and large-scale epidemic affecting the human population. It follows the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. This novel SARS-CoV-2 employs the angiotensin-converting enzyme 2 (ACE2) receptor, like SARS-CoV, and spreads principally in the respiratory tract. The viral spike (S) protein of coronaviruses facilities the attachment to the cellular receptor, entrance, and membrane fusion. The S protein is a glycoprotein and is critical to elicit an immune response. Glycosylation is a biologically significant post-translational modification in virus surface proteins. These glycans play important roles in the viral life cycle, structure, immune evasion, and cell infection. However, it is necessary to search for new information about viral behavior and immunological host's response after SARS-CoV-2 infection. The present review discusses the implications of the CoV-2 S protein glycosylation in the SARS-CoV-2/ACE2 interaction and the immunological response. Elucidation of the glycan repertoire on the spike protein can propel research for the development of an appropriate vaccine.
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http://dx.doi.org/10.1089/vim.2020.0174DOI Listing
April 2021

Freshness Quality and Shelf Life Evaluation of the Seaweed through Physical, Chemical, Microbiological, and Sensory Methods.

Foods 2021 Jan 18;10(1). Epub 2021 Jan 18.

Department of Chemical Engineering and Food Technology, Faculty of Sciences, University of Cádiz, Puerto Real, 11510 Cádiz, Spain.

In Europe, the consumption of seaweeds and derived products has increased in recent years, due to the expansion of Asian cuisine and the emergence of many top-level chefs. Often in collaboration with scientists, many have initiated a new gastronomy using algae. However, little is known about the quality and degree of freshness of seaweeds for direct consumption or fresh use. For this reason, different analytical methods were applied to test sea vegetables and other marine products. These methods included physical (a, pH, color, and texture), chemical (total volatile base nitrogen, TVB-N; and trimethylamine, TMA-N) parameters, microbiological count, and sensory evaluation. In this study, freshness quality and shelf life of the green seaweed (UR) was evaluated during a 12-day period, stored at 4 and 16 °C. The parameters that proved to be most useful for evaluating its freshness were the TVB, TMA, microbiological, and sensory analyses. The physicochemical and microbiological parameters established a shelf life of UR of 6 days for a storage temperature of 16 °C and up to 10 days for a storage temperature of 4 °C. The changes that UR undergoes during its storage from the sensory point of view are more pronounced than those produced from the physicochemical point of view, which can condition its applications.
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http://dx.doi.org/10.3390/foods10010181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831315PMC
January 2021

Ivabradine induces cardiac protection by preventing cardiogenic shock-induced extracellular matrix degradation.

Rev Esp Cardiol (Engl Ed) 2020 Oct 29. Epub 2020 Oct 29.

Unidad de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain; Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain. Electronic address:

Introduction And Objectives: Ivabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation.

Methods: In a porcine model of cardiogenic shock, we studied the effects of ivabradine on heart integrity, the levels of MMP-9 and EMMPRIN, and the stability of caveolin-3/HCN4 protein complexes with EMMPRIN.

Results: Administration of 0.3 mg/kg ivabradine significantly reduced cardiogenic shock-induced ventricular necrosis and expression of MMP-9 without affecting EMMPRIN mRNA, protein, or protein glycosylation (required for MMP activation). However, ivabradine increased the levels of the caveolin-3/LG-EMMPRIN (low-glycosylated EMMPRIN) and caveolin-3/HCN4 protein complexes and decreased that of a new complex between HCN4 and high-glycosylated EMMPRIN formed in response to cardiogenic shock. We next tested whether caveolin-3 can bind to HCN4 and EMMPRIN and found that the HCN4/EMMPRIN complex was preserved when we silenced caveolin-3 expression, indicating a direct interaction between these 2 proteins. Similarly, EMMPRIN-silenced cells showed a significant reduction in the binding of caveolin-3/HCN4, which regulates the I(f) current, suggesting that, rather than a direct interaction, both proteins bind to EMMPRIN.

Conclusions: In addition to inhibition of the I(f) current, ivabradine may induce cardiac protection by inhibiting ECM degradation through preservation of the caveolin-3/LG-EMMPRIN complex and control heart rate by stabilizing the caveolin-3/HCN4 complex.
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http://dx.doi.org/10.1016/j.rec.2020.09.012DOI Listing
October 2020

Differential effects of nutrient enrichment on carbon metabolism and dissolved organic carbon (DOC) fluxes in macrophytic benthic communities.

Mar Environ Res 2020 Dec 8;162:105179. Epub 2020 Oct 8.

Department of Biology, Faculty of Marine and Environmental Sciences, University of Cadiz, International Campus of Excellence of the Sea (CEIMAR), 11510, Puerto Real (Cádiz), Spain.

Nutrient enrichment can alter negatively benthic communities and reduce their ecological services. This study explores in two contrasting seasons (winter and summer), the effects of in situ nutrient enrichment at the community level on carbon metabolism and dissolved organic carbon (DOC) fluxes in two benthic communities dominated by the seagrass Cymodocea nodosa and by the macroalga Caulerpa prolifera. Under nutrient enrichment, C. nodosa increased total community biomass and diversity in summer, while net community production shifted from net autotrophic to net heterotrophic in winter. In contrast, C. prolifera became heterotrophic in summer, while no significant effects were found in winter. Regarding DOC fluxes, nutrient enrichment shifted C. nodosa from net DOC consumer in winter to a strong net DOC producer in summer, while C. prolifera seemed unaffected. Therefore, nutrient enrichment can promote conditional effects (positive, negative or neutral) in coastal areas depending both on macrophyte assemblages and season.
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http://dx.doi.org/10.1016/j.marenvres.2020.105179DOI Listing
December 2020

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

J Perinat Med 2020 11;48(9):950-958

Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.
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http://dx.doi.org/10.1515/jpm-2020-0355DOI Listing
November 2020

Nanomechanics of graphene oxide-bacteriophage based self-assembled porous composites.

Sci Rep 2020 09 24;10(1):15618. Epub 2020 Sep 24.

Queen Mary University of London, School of Engineering and Materials Science, London, E1 4NS, UK.

Graphene oxide, integrated with the filamentous bacteriophage M13, forms a 3D large-scale multifunctional porous structure by self-assembly, with considerable potential for applications. We performed Raman spectroscopy under pressure on this porous composite to understand its fundamental mechanics. The results show that at low applied pressure, the [Formula: see text] bonds of graphene oxide stiffen very little with increasing pressure, suggesting a complicated behaviour of water intercalated between the graphene layers. The key message of this paper is that water in a confined space can have a significant impact on the nanostructure that hosts it. We introduced carbon nanotubes during the self-assembly of graphene oxide and M13, and a similar porous macro-structure was observed. However, in the presence of carbon nanotubes, pressure is transmitted to the [Formula: see text] bonds of graphene oxide straightforwardly as in graphite. The electrical conductivity of the composite containing carbon nanotubes is improved by about 30 times at a bias voltage of 10 V. This observation suggests that the porous structure has potential in applications where good electrical conductivity is desired, such as sensors and batteries.
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http://dx.doi.org/10.1038/s41598-020-72372-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515913PMC
September 2020

Ivabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial Infarction.

Int J Mol Sci 2020 Sep 8;21(18). Epub 2020 Sep 8.

Cardiology Department, Universidad Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), 28223 Madrid, Spain.

Ivabradine can reduce heart rate through inhibition of the current I() by still unexplored mechanisms. In a porcine model of ischemia reperfusion (IR), we found that treatment with 0.3 mg/kg Ivabradine increased plasma release of microvesicles (MVs) over Placebo, as detected by flow cytometry of plasma isolated from pigs 7 days after IR, in which a tenfold increase of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) containing (both high and low-glycosylated) MVs, was detected in response to Ivabradine. The source of MVs was investigated, finding a 37% decrease of CD31+ endothelial cell derived MVs, while CD41+ platelet MVs remained unchanged. By contrast, Ivabradine induced the release of HCN4+ (mostly cardiac) MVs. While no differences respect to EMMPRIN as a cargo component were found in endothelial and platelet derived MVs, Ivabradine induced a significant release of EMMPRIN+/HCN4+ MVs by day 7 after IR. To test the role of EMMPRIN+ cardiac MVs (EMCMV), H9c2 cell monolayers were incubated for 24 h with 10 EMCMVs, reducing apoptosis, and increasing 2 times cell proliferation and 1.5 times cell migration. The in vivo contribution of Ivabradine-induced plasma MVs was also tested, in which 10 MVs isolated from the plasma of pigs treated with Ivabradine or Placebo 7 days after IR, were injected in pigs under IR, finding a significant cardiac protection by increasing left ventricle ejection fraction and a significant reduction of the necrotic area. In conclusion ivabradine induces cardiac protection by increasing at least the release of EMMPRIN containing cardiac microvesicles.
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http://dx.doi.org/10.3390/ijms21186566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555962PMC
September 2020

Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction.

Biomolecules 2020 08 9;10(8). Epub 2020 Aug 9.

Cardiology Department, Universidad Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), CIBERCV, 28223 Madrid, Spain.

Toll-like receptor 4 (TLR4) contributes to the pathogenesis of coronary ischemia/reperfusion (IR). To test whether the new TLR4 antagonist, ApTOLL, may prevent coronary IR damage, we administered 0.078 mg/kg ApTOLL or Placebo in pigs subjected to IR, analyzing the levels of cardiac troponins, matrix metalloproteinases, pro-, and anti-inflammatory cytokines, heart function, and tissue integrity over a period of 7 days after IR. Our results show that ApTOLL reduced cardiac troponin-1 24 h after administration, improving heart function, as detected by a significant recovery of the left ventricle ejection fraction (LVEF) and the shortening fraction (FS) cardiac parameters. The extension of necrotic and fibrotic areas was also reduced, as detected by Evans blue/2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin/Eosine, and Masson Trichrome staining of heart sections, together with a significant reduction in the expression of the extracellular matrix-degrading, matrix metalloproteinase 9. Finally, the expression of the following cytokines, CCL1, CCL2, MIP1-A-B, CCL5, CD40L, C5/C5A, CXCL1, CXCL10, CXCL11, CXCL12, G-CSF, GM-CSF, ICAM-1, INF-g, IL1-a, ILI-b, IL-1Ra, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, IL16, IL17-A, IL17- E, IL18, IL21, IL27, IL32, MIF, SERPIN-E1, TNF-a, and TREM-1, were also assayed, detecting a pronounced decrease of pro-inflammatory cytokines after 7 days of treatment with ApTOLL. Altogether, our results show that ApTOLL is a promising new tool for the treatment of acute myocardial infarction (AMI).
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http://dx.doi.org/10.3390/biom10081167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464507PMC
August 2020

PCSK9 and HS-CRP Predict Progression of Aortic Stenosis in Patients with Stable Coronary Artery Disease.

J Cardiovasc Transl Res 2021 Apr 23;14(2):238-245. Epub 2020 Jun 23.

Department of Cardiology, IIS-Fundación Jiménez Díaz, Avenida, Reyes Católicos 2, 28040, Madrid, Spain.

It is essential to study the factors associated with the evolution of aortic stenosis progression (ASP) to develop therapies that could reduce it. We studied 283 patients 6 months after acute coronary syndrome (ACS). ASP was defined as an increase in the maximum aortic velocity of at least 0.5 m/s between the echocardiogram performed during ACS hospitalization and the last one recorded in the electronic medical registry. The median follow-up was 72.4 months. Twenty patients (7%) had ASP. A multivariate binary logistic regression analysis was performed showing that PCSK9 plasma levels (OR, 0.668 CI (0.457-0.977); p = 0.038), HS-CRP (OR, 1.034 CI (1.005-1.063); p = 0.022), the presence of dyslipidemia (OR, 4.622 CI (1.285-16.618); p = 0.019), the history of PAD (OR, 9.453 CI (1.703-52.452); p = 0.010), and GFR (OR, 0.962 CI (0.939-0.986); p = 0.002) were independent predicting factors of ASP. In patients with ischemic heart disease, low plasma levels of PCSK9 and elevated levels of HS-CRP are independent predictors of ASP.
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http://dx.doi.org/10.1007/s12265-020-10050-3DOI Listing
April 2021

A spatially explicit analysis of chronic diseases in small areas: a case study of diabetes in Santiago, Chile.

Int J Health Geogr 2020 06 23;19(1):24. Epub 2020 Jun 23.

Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago, Chile.

Background: There is a strong spatial correlation between demographics and chronic diseases in urban areas. Thus, most of the public policies aimed at improving prevention plans and optimizing the allocation of resources in health networks should be designed specifically for the socioeconomic reality of the population. One way to tackle this challenge is by exploring within a small geographical area the spatial patterns that link the sociodemographic attributes that characterize a community, its risk of suffering chronic diseases, and the accessibility of health treatment. Due to the inherent complexity of cities, soft clustering methods are recommended to find fuzzy spatial patterns. Our main motivation is to provide health planners with valuable spatial information to support decision-making. For the case study, we chose to investigate diabetes in Santiago, Chile.

Methods: To deal with spatiality, we combine two statistical techniques: spatial microsimulation and a self-organizing map (SOM). Spatial microsimulation allows spatial disaggregation of health indicators data to a small area level. In turn, SOM, unlike classical clustering methods, incorporates a learning component through neural networks, which makes it more appropriate to model complex adaptive systems, such as cities. Thus, while spatial microsimulation generates the data for the analysis, the SOM method finds the relevant socio-economic clusters. We selected age, sex, income, prevalence of diabetes, distance to public health services, and type of health insurance as input variables. We used public surveys as input data.

Results: We found four significant spatial clusters representing 75 percent of the whole population in Santiago. Two clusters correspond to people with low educational levels, low income, high accessibility to public health services, and a high prevalence of diabetes. However, one presents a significantly higher level of diabetes than the other. The second pair of clusters is made up of people with high educational levels, high income, and low prevalence of diabetes. What differentiates both clusters is accessibility to health centers. The average distance to the health centers of one group almost doubles that of the other.

Conclusions: In this study, we combined two statistical techniques: spatial microsimulation and selforganising maps to explore the relationship between diabetes and socio-demographics in Santiago, Chile. The results have allowed us to corroborate the importance of the spatial factor in the analysis of chronic diseases as a way of suggesting differentiated solutions to spatially explicit problems. SOM turned out to be a good choice to deal with fuzzy health and socioeconomic data. The method explored and uncovered valuable spatial patterns for health decision-making. In turn, spatial microsimulation.
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http://dx.doi.org/10.1186/s12942-020-00217-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310447PMC
June 2020

Prevalence of the potential drug-drug interactions between pangenotypic direct-acting antivirals and the concomitant medications associated with patients with chronic hepatitis C virus infection in Spain.

Gastroenterol Hepatol 2019 Oct 23;42(8):465-475. Epub 2019 Aug 23.

Farmacia Hospitalaria, Hospital de Valme, AGS Sur de Sevilla, España.

Objective: To determine the comorbidity and potential for drug-drug interactions (DDIs) among pangenotypic direct-acting-antivirals (pDAAs) and the concomitant medications associated with chronic hepatitis C (CHC) patients in routine clinical practice in Spain.

Methods: Retrospective observational study. Included patients were ≥18 years, diagnosed with CHC, on antiviral treatment and required medical attention during 2017. Two groups were differentiated according to age ranges (<50 and ≥50 years). The variables collected were: age, gender, general/specific comorbidity, concomitant medication and potential DDIs (www.hep-druginteractions.org). The pDAAs analysed were: a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Bivariate statistical analysis, P<.05.

Results: 3,430 patients with a mean age of 56.9 years and 60.3% males were enrolled. The average Charlson index was 0.8. Age range distribution: 18-49 years (28.9%) and ≥50 years (71.1%). The average number of medications per patient/year was 3.1 (SD 2.6). The total percentage of potential DDIs was: 8.6% minor DDIs, 40.5% clinically significant DDIs and 10.0% contraindicated medication. These DDIs were greater in patients ≥50 years (8.6%, 43.8% and 12.4%, respectively, P<.001). For all ages, SOF/VEL showed a lower percentage of: minor interactions (1.3% vs. 6.6% and 5.9%, P<.001); clinically significant interactions (53.4%, vs. 77.4% and 66.3%, P<.001) and contraindicated medication (1.7% vs. 8.3% and 10.7%, P<.001) compared to GLE/PIB and SOF/VEL/VOX, respectively.

Conclusions: Patients with CHC present high comorbidity and concomitant medication use, particularly elderly patients, thus implying a greater exposure to potential DDIs. Although the DDI rate was considerable with the three combinations analysed, SOF/VEL showed a lower number of clinically significant interactions.
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http://dx.doi.org/10.1016/j.gastrohep.2019.03.014DOI Listing
October 2019

Pressure-induced spin transition and site-selective metallization in CoCl.

Sci Rep 2019 Apr 1;9(1):5448. Epub 2019 Apr 1.

Universidad de Cantabria, MALTA Consolider Team - DCITIMAC, Santander, 39005, Spain.

The interplay between spin states and metallization in compressed CoCl is investigated by combining diffraction, resistivity and spectroscopy techniques under high-pressure conditions and ab-initio calculations. A pressure-induced metallization along with a Co high-spin (S = 3/2) to low-spin (S = 1/2) crossover transition is observed at high pressure near 70 GPa. This metallization process, which is associated with the p-d charge-transfer band gap closure, maintains the localization of 3d electrons around Co, demonstrating that metallization and localized Co -3d low-spin magnetism can coexist prior to the full 3d-electron delocalization (Mott-Hubbard d-d breakdown) at pressures greater than 180 GPa.
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http://dx.doi.org/10.1038/s41598-019-41337-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443712PMC
April 2019

Differential expression of circulating miRNAs as a novel tool to assess BAG3-associated familial dilated cardiomyopathy.

Biosci Rep 2019 03 15;39(3). Epub 2019 Mar 15.

Univ Puerta del Mar, School of Medicine, Cadiz, Spain

A new familial dilated cardiomyopathy (FDCM) was found related to mutations in gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM and circulating miRNAs may have diagnostic and prognostic value in a small cohort of familial related individuals carrying a BAG3 mutation (BAG3+) and/or diagnosed of dilated cardiomyopathy (DCM) (DCM+). The analysis of 1759 circulating miRNAs showed significant differences between BAG3+ and BAG3- individuals for miRNAs mir-3191-3p, 6769b-3p, 1249-ep, 154-5p, 6855-5p, and 182-5p, while comparisons between BAG3+/DCM+ versus BAG3+/DCM- were restricted to miRNAs mir-154-5p, 6885-5p, and 182-5p, showing significant correlation with systolic and diastolic blood pressure, A wave, left atrium length, and left atrium area. Additionally, when stratified by gender and age, miRNAs were statistically correlated with critical parameters, including left ventricle ejection fraction (LVEF) and ventricular diameter, in women and young men. Likewise, 56% of BAG3+/DCM+, significantly co-expressed mir-154-5p and mir-182-5p, and a slight 4% did not express such combination, suggesting that co-expression of mir-154-5p and mir-182-5p may potentially show diagnostic value. Further studies will require long-term follow-up, and validation in larger populations.
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http://dx.doi.org/10.1042/BSR20180934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418398PMC
March 2019

Effect of In Situ short-term temperature increase on carbon metabolism and dissolved organic carbon (DOC) fluxes in a community dominated by the seagrass Cymodocea nodosa.

PLoS One 2019 14;14(1):e0210386. Epub 2019 Jan 14.

Department of Biology, Faculty of Marine and Environmental Sciences, University of Cadiz, Puerto Real (Cádiz), Spain.

Seagrasses form one of the most productive and threatened ecosystems worldwide because of global change and anthropogenic pressures. The frequency of extreme climatic events, such as heat waves, are expected to increase and may drive even more adverse effects than gradual warming. This study explores for the first time the effects of a sudden and temporary increase of temperature in situ on carbon metabolism and dissolved organic carbon (DOC) fluxes in a community dominated by a seagrass (Cymodocea nodosa) during two contrasting seasons (winter and summer). Results showed a positive correlation between temperature and seagrass production between seasons, while the experimental sudden and temporary increase in water temperature did not produce significant differences in carbon community metabolism and DOC fluxes in winter. In contrast, high temperature conditions in summer enhanced significantly the net community production and affected positively to DOC fluxes. Hence, this study indicates that a sudden and temporary increase in water temperature, which characterize marine heat waves, in temperate areas may enhance the autotrophic metabolism of seagrass communities and can yield an increase in the DOC released, in contrast to previous researches suggesting solely negative effects on seagrasses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210386PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331083PMC
October 2019

Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide.

Int J Mol Sci 2018 Oct 19;19(10). Epub 2018 Oct 19.

Cardiology Department, University Francisco de Vitoria/Hospital Ramón y Cajal Research Unit (IRYCIS), CIBERCV, 28223 Madrid, Spain.

Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement. We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis. Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.
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http://dx.doi.org/10.3390/ijms19103248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214015PMC
October 2018

Marine forests of the Mediterranean-Atlantic Cystoseira tamariscifolia complex show a southern Iberian genetic hotspot and no reproductive isolation in parapatry.

Sci Rep 2018 Jul 11;8(1):10427. Epub 2018 Jul 11.

Center of Marine Sciences (CCMAR), CIMAR Laboratorio Associado, Campus de Gambelas, Universidade do Algarve, 8005-139, Faro, Portugal.

Climate-driven range-shifts create evolutionary opportunities for allopatric divergence and subsequent contact, leading to genetic structuration and hybrid zones. We investigate how these processes influenced the evolution of a complex of three closely related Cystoseira spp., which are a key component of the Mediterranean-Atlantic seaweed forests that are undergoing population declines. The C. tamariscifolia complex, composed of C. tamariscifolia s.s., C. amentacea and C. mediterranea, have indistinct boundaries and natural hybridization is suspected. Our aims are to (1) infer the genetic structure and diversity of these species throughout their distribution ranges using microsatellite markers to identify ancient versus recent geographical populations, contact zones and reproductive barriers, and (2) hindcast past distributions using niche models to investigate the influence of past range shifts on genetic divergence at multiple spatial scales. Results supported a single, morphologically plastic species the genetic structure of which was incongruent with a priori species assignments. The low diversity and low singularity in northern European populations suggest recent colonization after the LGM. The southern Iberian genetic hotspot most likely results from the role of this area as a climatic refugium or a secondary contact zone between differentiated populations or both. We hypothesize that life-history traits (selfing, low dispersal) and prior colonization effects, rather than reproductive barriers, might explain the observed genetic discontinuities.
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http://dx.doi.org/10.1038/s41598-018-28811-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041324PMC
July 2018

Balloon Pulmonary Angioplasty for Inoperable Patients With Chronic Thromboembolic Pulmonary Hypertension. Observational Study in a Referral Unit.

Rev Esp Cardiol (Engl Ed) 2019 Mar 30;72(3):224-232. Epub 2018 May 30.

Servicio de Cardiología, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.

Introduction And Objectives: Balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is becoming widely accepted. Procedural refinement has reduced complications. Our primary objective was to analyze the results and complications of the first national BPA program.

Methods: Observational, prospective series that included all consecutive BPA procedures in inoperable CTEPH patients between May 2013 and February 2017 performed at a single institution. We analyzed clinical and hemodynamic improvement, reperfusion pulmonary edema, and mortality.

Results: We performed 156 BPA sessions in 46 patients. Pulmonary vascular resistance was reduced by 44% (10.1 ± 4.9 vs 5.6 ± 2.2 WU; P < .001) and mean pulmonary arterial pressure by 23.6% (49.5 ± 12 vs 37.8 ± 9mmHg; P < .001); cardiac index rose by 17.1% (2.3 vs 2.7 L/min/m; P = .002), N-terminal pro-B-type natriuretic peptide levels were reduced by 79.2% (1233 ± 1327 vs 255.5 ± 318 pg/dL; P < .001) and the 6-minute walk test distance improved by 74 meters (394 vs 468 m; P = .001). Reperfusion pulmonary edema developed after 9 interventions (5.8%) and 1 patient died (mortality 2.1%).

Conclusions: Due to its current refinement, BPA has become a safe and effective treatment for inoperable CTEPH that improves hemodynamics, functional status, and biomarkers with a low rate of severe periprocedural complications and mortality.
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http://dx.doi.org/10.1016/j.rec.2018.02.020DOI Listing
March 2019

Effects of ocean acidification and hydrodynamic conditions on carbon metabolism and dissolved organic carbon (DOC) fluxes in seagrass populations.

PLoS One 2018 8;13(2):e0192402. Epub 2018 Feb 8.

Department of Biology, Faculty of Marine and Environmental Sciences, University of Cadiz, Puerto Real, Cádiz, Spain.

Global change has been acknowledged as one of the main threats to the biosphere and its provision of ecosystem services, especially in marine ecosystems. Seagrasses play a critical ecological role in coastal ecosystems, but their responses to ocean acidification (OA) and climate change are not well understood. There have been previous studies focused on the effects of OA, but the outcome of interactions with co-factors predicted to alter during climate change still needs to be addressed. For example, the impact of higher CO2 and different hydrodynamic regimes on seagrass performance remains unknown. We studied the effects of OA under different current velocities on productivity of the seagrass Zostera noltei, using changes in dissolved oxygen as a proxy for the seagrass carbon metabolism, and release of dissolved organic carbon (DOC) in a four-week experiment using an open-water outdoor mesocosm. Under current pH conditions, increasing current velocity had a positive effect on productivity, but this depended on shoot density. However, this positive effect of current velocity disappeared under OA conditions. OA conditions led to a significant increase in gross production rate and respiration, suggesting that Z. noltei is carbon-limited under the current inorganic carbon concentration of seawater. In addition, an increase in non-structural carbohydrates was found, which may lead to better growing conditions and higher resilience in seagrasses subjected to environmental stress. Regarding DOC flux, a direct and positive relationship was found between current velocity and DOC release, both under current pH and OA conditions. We conclude that OA and high current velocity may lead to favourable growth scenarios for Z. noltei populations, increasing their productivity, non-structural carbohydrate concentrations and DOC release. Our results add new dimensions to predictions on how seagrass ecosystems will respond to climate change, with important implications for the resilience and conservation of these threatened ecosystems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192402PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805273PMC
April 2018

Bright Photon Upconversion on Composite Organic Lanthanide Molecules through Localized Thermal Radiation.

J Phys Chem Lett 2017 Dec 9;8(23):5695-5699. Epub 2017 Nov 9.

Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, 637371 Singapore.

Converting low-energy photons via thermal radiation can be a potential approach for utilizing infrared (IR) photons to improve photovoltaic efficiency. Lanthanide-containing materials have achieved great progress in IR-to-visible photon upconversion (UC). Herein, we first report bright photon, tunable wavelength UC through localized thermal radiation at the molecular scale with low excitation power density (<10 W/cm) realized on lanthanide complexes of perfluorinated organic ligands. This is enabled by engineering the pathways of nonradiative de-excitation and energy transfer in a composite of ytterbium and terbium perfluoroimidodiphosphinates. The IR-excited thermal UC and wavelength control is realized through the terbium activators sensitized by the ytterbium sensitizers having high luminescence efficiency. The metallic molecular composite thus can be a potential energy material in the use of the IR solar spectrum for thermal photovoltaic applications.
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http://dx.doi.org/10.1021/acs.jpclett.7b02513DOI Listing
December 2017

Global and local disturbances interact to modify seagrass palatability.

PLoS One 2017 16;12(8):e0183256. Epub 2017 Aug 16.

Departament of Biology (Division of Ecology), Faculty of Marine and Environmental Sciences, University of Cádiz, Puerto Real, Spain.

Global change, such as warming and ocean acidification, and local anthropogenic disturbances, such as eutrophication, can have profound impacts on marine organisms. However, we are far from being able to predict the outcome of multiple interacting disturbances on seagrass communities. Herbivores are key in determining plant community structure and the transfer of energy up the food web. Global and local disturbances may alter the ecological role of herbivory by modifying leaf palatability (i.e. leaf traits) and consequently, the feeding patterns of herbivores. This study evaluates the main and interactive effects of factors related to global change (i.e. elevated temperature, lower pH levels and associated ocean acidification) and local disturbance (i.e. eutrophication through ammonium enrichment) on a broad spectrum of leaf traits using the temperate seagrass Cymodocea nodosa, including structural, nutritional, biomechanical and chemical traits. The effect of these traits on the consumption rates of the generalist herbivore Paracentrotus lividus (purple sea urchin) is evaluated. The three disturbances of warming, low pH level and eutrophication, alone and in combination, increased the consumption rate of seagrass by modifying all leaf traits. Leaf nutritional quality, measured as nitrogen content, was positively correlated to consumption rate. In contrast, a negative correlation was found between feeding decisions by sea urchins and structural, biomechanical and chemical leaf traits. In addition, a notable accomplishment of this work is the identification of phenolic compounds not previously reported for C. nodosa. Our results suggest that global and local disturbances may trigger a major shift in the herbivory of seagrass communities, with important implications for the resilience of seagrass ecosystems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183256PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558941PMC
October 2017

Sensitization, energy transfer and infra-red emission decay modulation in Yb-doped NaYF nanoparticles with visible light through a perfluoroanthraquinone chromophore.

Sci Rep 2017 07 11;7(1):5066. Epub 2017 Jul 11.

Dpto. CITIMAC, Universidad de Cantabria, Facultad de Ciencias, Avda. Los Castros, s/n 39005, Santander, Spain.

Infra-red emission (980 nm) of sub 10 nm Yb-doped NaYF nanoparticles has been sensitized through the excitation of 2-hydroxyperfluoroanthraquinone chromophore (1,2,3,4,5,6,7-heptafluro-8-hydroxyanthracene-9,10-dione) functionalizing the nanoparticle surface. The sensitization is achieved with a broad range of visible light excitation (400-600 nm). The overall near infra-red (NIR) emission intensity of Yb ions is increased by a factor 300 as a result of the broad and strong absorption of the chromophore compared with ytterbium's intrinsic absorption. Besides the Yb NIR emission, the hybrid composite shows organic chromophore-based visible emission in the orange-red region of the spectrum. We observe the energy migration process from the sensitized Yb ions at the surface to those in the core of the particle using time-resolved optical spectroscopy. This highlights that the local environments for emitting Yb ions at the surface and center of the nanoparticle are not identical, which causes important differences in the NIR emission dynamics. Based on the understanding of these processes, we suggest a simple strategy to control and modulate the decay time of the functionalized Yb-doped nanoparticles over a relatively large range by changing physical or chemical parameters in this model system.
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http://dx.doi.org/10.1038/s41598-017-05350-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505979PMC
July 2017

Profiling of Phenolic Natural Products in the Seagrass Zostera noltei by UPLC-MS.

Nat Prod Commun 2017 May;12(5):687-690

Seagrasses are marine plants that play important ecological functions in coastal ecosystems. The species Zostera noltei is widely distributed along the European coasts thriving in a variety of environmental conditions. In this study, the phenolic natural products of Z. noltei have been analyzed quantitatively by using UPLC-MS. Plants from the Natural Park of the Bay of Cadiz (Spain) were shown to contain rosmarinic acid (1) and the flavonoids apigenin-7-0- glucoside (2), luteolin-7-sulfate (7), apigenin-7-sulfate (8), diosmetin-7-sulfate (9), and acacetin-7-sulfate (10). The analysis by UPLC-MS of extracts allowed the quantification of all the compounds and evidenced the intraspecific variations in the profile of natural products among plants collected at different dates and locations within the Bay. The flavonoids 2, and 7-10 were present in all the analyzed samples with a total flavonoid content in the range 12.8-72.3 mg/g dry wt, while rosmarinic acid (1) was only present in some samples, reaching up to 19.6 mg/g dry wt. A distinctive feature of plants from the Bay of Cadiz is the common presence of apigenin-7-sulfate (8) as major flavonoid, differing from plants from other regions whose major flavonoid is diosmetin-7-sulfate (9).
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May 2017

Spatial variability and response to anthropogenic pressures of assemblages dominated by a habitat forming seaweed sensitive to pollution (northern coast of Alboran Sea).

Mar Pollut Bull 2016 Apr 15;105(1):255-64. Epub 2016 Feb 15.

Departamento de Biología, Área de Ecología, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, 11510, Puerto Real, Cádiz, Spain.

The Cystoseira ericaefolia group is conformed by three species: C. tamariscifolia, C. mediterranea and C. amentacea. These species are among the most important habitat forming species of the upper sublittoral rocky shores of the Mediterranean Sea and adjacent Atlantic coast. This species group is sensitive to human pressures and therefore is currently suffering important losses. This study aimed to assess the influence of anthropogenic pressures, oceanographic conditions and local spatial variability in assemblages dominated by C. ericaefolia in the Alboran Sea. The results showed the absence of significant effects of anthropogenic pressures or its interactions with environmental conditions in the Cystoseira assemblages. This fact was attributed to the high spatial variability, which is most probably masking the impact of anthropogenic pressures. The results also showed that most of the variability occurred on at local levels. A relevant spatial variability was observed at regional level, suggesting a key role of oceanographic features in these assemblages.
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http://dx.doi.org/10.1016/j.marpolbul.2016.02.017DOI Listing
April 2016

Comparison of Implantable Cardioverter Defibrillator Therapy and Medical Therapy in Individuals Aged 75 and Older.

J Am Geriatr Soc 2016 Feb;64(2):440-2

Department of Cardiology, Hospital Universitario Fundación Jiménez Díaz-Quirónsalud, Universidad Autónoma de Madrid, Madrid, Spain.

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http://dx.doi.org/10.1111/jgs.13978DOI Listing
February 2016

Pressure-Induced Amorphization and a New High Density Amorphous Metallic Phase in Matrix-Free Ge Nanoparticles.

Nano Lett 2015 Nov 20;15(11):7334-40. Epub 2015 Oct 20.

School of Physics and Astronomy, Queen Mary University of London , Mile End Road, London E1 4NS, United Kingdom.

Over the last two decades, it has been demonstrated that size effects have significant consequences for the atomic arrangements and phase behavior of matter under extreme pressure. Furthermore, it has been shown that an understanding of how size affects critical pressure-temperature conditions provides vital guidance in the search for materials with novel properties. Here, we report on the remarkable behavior of small (under ~5 nm) matrix-free Ge nanoparticles under hydrostatic compression that is drastically different from both larger nanoparticles and bulk Ge. We discover that the application of pressure drives surface-induced amorphization leading to Ge-Ge bond overcompression and eventually to a polyamorphic semiconductor-to-metal transformation. A combination of spectroscopic techniques together with ab initio simulations were employed to reveal the details of the transformation mechanism into a new high density phase-amorphous metallic Ge.
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http://dx.doi.org/10.1021/acs.nanolett.5b02627DOI Listing
November 2015

Synthesis, Characterization, and Application of Core-Shell [email protected](Yb, Er) and [email protected](Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents.

Bioconjug Chem 2016 Feb 14;27(2):319-28. Epub 2015 Aug 14.

King's College London , Division of Imaging Sciences and Biomedical Engineering, Fourth Floor Lambeth Wing, St. Thomas Hospital, London, SE1 7EH, United Kingdom.

Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise [email protected] core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including [email protected](Yb, Er) and [email protected](Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged [email protected](Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs [email protected](Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.
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http://dx.doi.org/10.1021/acs.bioconjchem.5b00338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759617PMC
February 2016

Comparison of pharmacological treatment alone versus treatment combined with cardiac resynchronization therapy in patients over 75 years.

J Interv Card Electrophysiol 2015 Jun 17;43(1):13-20. Epub 2015 Feb 17.

Hospital Universitario Fundación Jiménez Díaz - idcsalud, Universidad Autónoma de Madrid, Madrid, Spain.

Background: The role of cardiac resynchronization therapy (CRT) in patients aged ≥75 years is not well established.

Methods: We identified 607 patients aged ≥75 years with left ventricular ejection fraction (LVEF) of ≤35 %, of whom 78 met the guidelines for indication of CRT. Based on the decision of the patients or attending cardiologists, 34 patients received a CRT defibrillator (CRT-D).

Results: The age of patients with a CRT indication was 80 ± 4 years, and 73 % were males. As compared with patients on medical therapy, CRT-D patients were younger (79 ± 3 vs. 83 ± 4, P < 0.001), had lower LVEF (23 ± 7 vs. 27 ± 7 %, P = 0.008) and higher rate of decompensated heart failure episodes (77 vs. 55 %, P = 0.04), were more frequently New York Heart Association (NYHA) class III-IV (53 vs. 25 %, P = 0.01), and were more likely to be on beta-blockers (88 vs. 66 %, P = 0.023), anticoagulants (61 vs. 32 % P = 0.02), and anti-aldosterone drugs (82 vs. 50 %, P = 0.003). After a median follow-up of 26 months, seven patients in the CRT-D group (21 %) and 20 non-CRT patients (46 %) died (hazard ratio (HR) 0.16 [95 % confidence interval (CI) 0.06-0.46]). The end point of mortality or hospitalization was not reduced because of a similar rate of hospitalizations for heart failure of CRT-D patients. Four CRT-D patients (12 %) had received appropriate device therapy, and one had been inappropriately discharged. During follow-up, 44 % of CRT-D patients improved their LVEF by >40 %.

Conclusion: CRT-D is potentially of benefit in terms of mortality in our population; this effect persists after correction for use of beta-blockers. In patients ≥75 years, CRT indications should be similar to those accepted for younger subjects.
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http://dx.doi.org/10.1007/s10840-015-9979-2DOI Listing
June 2015

Concentration dependence of the up- and down-conversion emission colours of Er(3+)-doped Y2O3: a time-resolved spectroscopy analysis.

Phys Chem Chem Phys 2014 Oct 29;16(38):20957-63. Epub 2014 Aug 29.

School of Physics and Astronomy, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.

In this paper, a series of Er(3+)-doped Y2O3 samples are systematically investigated, focusing on the effect of the doping concentration on the emission lifetime and spectrum under both 488 nm and 980 nm excitations. Decay times of the (4)S3/2 and (4)F9/2 emitting states under 488 nm and 980 nm excitations are found to be different and concentration dependent. We explain these variations in terms of the changes in the up-conversion routes caused by the predominance of energy exchanges that involve the lowest lying excited states.
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http://dx.doi.org/10.1039/c4cp02028fDOI Listing
October 2014