Analysis of printing parameters for metal additive manufactured parts through Direct Ink Writing process

Direct Ink Writing is an Additive Manufacturing process in which a metal ink is continuously extruded to built-up a green metal part. Therefore, a debinding and sintering process is required to obtain the final metal part. This thermal process produces a shrinkage of the green printed part according to several material and printing parameters. In this paper, the influence of printing process planning on the width of printed rods for a copper ink is analyzed by means of a Design of Experiments procedure to optimize the printing and equipment parameters and characterize the shrinkage after the sintering processPeer ReviewedPostprint (published version

The role of red blood cell exchange for severe imported malaria in the artesunate era: a retrospective cohort study in a referral centre

BACKGROUND: Intravenous artesunate has replaced quinine as the first-line therapy for severe imported malaria, given its anti-malarial superiority shown in clinical trials conducted in endemic countries. Evidence for red blood cell (RBC) exchange in patients with severe malaria treated with artesunate is lacking. This retrospective cohort study describes the experience at Hospital Clinic of Barcelona with the use of artesunate for severe malaria and the joint use of RBC exchange in selected cases. METHODS: Patients treated for severe malaria at Hospital Clinic of Barcelona between August 2013 and January 2015 were included in this retrospective study. Severe malaria was defined according to WHO criteria. Data were extracted from electronic hospital records. A log-linear mixed model approach was used to estimate parasite clearance times. RESULTS: Within the study period, 42 patients were diagnosed of malaria at this centre, of which 38 had Plasmodium falciparum (90.5 %). Sixteen patients (42 %) had severe malaria cases and were treated with intravenous artesunate. Four patients underwent RBC exchange within a period of 15 h after the first dose of artesunate (range 9-21 h). The procedure lasted a median of 2 h (IQR 1.8-2 h), using a median of 12 (IQR 11-14) units of packed RBCs to replace a median of 3794 ml (IQR 2977-4343). The technique was well-tolerated without haemodynamic complications. There were no deaths. The regression model showed an estimated time to 95 % decay of 21.6 h (95 % CI 17.3-28.8). When assessing effect modification by RBC exchange, there was no difference in the parasite elimination rate (p = 0.286). DISCUSSION AND CONCLUSION: In this study RBC exchange failed to show benefits in terms of parasite clearance probably due to the small number of patients analysed. The evidence for exchange transfusion remains limited

The aryl hydrocarbon receptor ligand FICZ improves left ventricular remodeling and cardiac function at the onset of pressure overload-Induced heart failure in mice

Adverse ventricular remodeling is the heart’s response to damaging stimuli and is linked to heart failure and poor prognosis. Formyl-indolo [3,2-b] carbazole (FICZ) is an endogenous ligand for the aryl hydrocarbon receptor (AhR), through which it exerts pleiotropic effects including protection against inflammation, fibrosis, and oxidative stress. We evaluated the effect of AhR activation by FICZ on the adverse ventricular remodeling that occurs in the early phase of pressure overload in the murine heart induced by transverse aortic constriction (TAC). Cardiac structure and function were evaluated by cardiac magnetic resonance imaging (CMRI) before and 3 days after Sham or TAC surgery in mice treated with FICZ or with vehicle, and cardiac tissue was used for biochemical studies. CMRI analysis revealed that FICZ improved cardiac function and attenuated cardiac hypertrophy. These beneficial effects involved the inhibition of the hypertrophic calcineurin/NFAT pathway, transcriptional reduction in pro-fibrotic genes, and antioxidant effects mediated by the NRF2/NQO1 pathway. Overall, our findings provide new insight into the role of cardiac AhR signaling in the injured heart.This research was supported by Grants SAF2017-84777-R, funded by the Ministry of Economy and Competitiveness (MINECO) of Spain, PID2020-113238RB-I00 funded by the Ministry of Science and Innovation (MCIN)/AEI/ 10.13039/501100011033 of Spain and the “European Union Next GenerationEU/PRTR”; PI20/01482-1 funded by the Instituto de Salud Carlos III, CB16/11/00222 funded by the Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV) and a Grant (Proyectos 2021) financed by the Universidad Francisco de Vitoria

Urinary exosomes reveal protein signatures in hypertensive patients with albuminuria

Albuminuria is an indicator of cardiovascular risk and renal damage in hypertensive individuals. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control and prevents development of new-onset-albuminuria. A significant number of patients, however, develop albuminuria despite chronic RAS blockade, and the physiopathological mechanisms are underexplored. Urinary exosomes reflect pathological changes taking place in the kidney. The objective of this work was to examine exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression, to find novel clues underlying its development. Patients were followed-up for three years and were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. Exosomal protein alterations between groups were identified by isobaric tag quantitation (iTRAQ). Confirmation was approached by target analysis (SRM). In total, 487 proteins were identified with high confidence. Specifically, 48 proteins showed an altered pattern in response to hypertension and/or albuminuria. Out of them, 21 proteins interact together in three main functional clusters: glycosaminoglycan degradation, coagulation and complement system, and oxidative stress. The identified proteins constitute potential targets for drug development and may help to define therapeutic strategies to evade albuminuria progression in hypertensive patients chronically treated.Instituto de Salud Carlos III, fondos FEDER/FSE (PI11/01401, PI13/01873, PI14/01841, IF08/3667-1, PI11-02239, PI 14/0917, PI11/02432, PI13/01746, PI14/01650, PI16/01334, PT13/0001/0013, CP09/00229, CP15/00129, CPII15/00027), Fundacion SENEFRO, Fundacion Conchita Rabago de Jimenez Diaz, and Redes Tematicas de Investigacion Cooperativa (fondos FEDER/FSE, RD12/0021/0001, RD12/0042/0071). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP).S

Characterization of methicillin-resistant Staphylococcus aureus strains colonizing the nostrils of Spanish children

Objective: To characterize the Staphylococcus aureus strains colonizing healthy Spanish children. Methods: Between March and July 2018, 1876 Spanish children younger than 14 years attending primary healthcare centers were recruited from rural and urban areas. Staphylococcus aureus colonization of the anterior nostrils was analyzed. MecA and mecC genes, antibiotic susceptibility, and genotyping according to the spa were determined in all strains, and the following toxins were examined: Panton-Valentine leucocidin (pvl), toxic shock syndrome toxin (tst), and exfoliative toxins (eta, etb, etd). Multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing were performed on methicillin-resistant Staphylococcus aureus (MRSA) strains, as well as pulsed-field gel electrophoresis (PFGE). Results: 619 strains were isolated in 1876 children (33%), and 92% of them were sent for characterization to the Spanish National Centre of Microbiology (n = 572). Twenty (3.5%) of these strains were mecA-positive. Several spa types were detected among MRSA, being t002 the most frequently observed (30%), associating with SCCmec IVc. Among MSSA, 33% were positive for tst, while only 0.73% were positive for pvl. The 20 MRSA strains were negative for pvl, and 6 (30%) harbored the tst gene. Conclusions: methicillin-resistant Staphylococcus aureus nasal colonization in Spanish children is rare, with t002 being the most observed spa type, associated with SCCmec IVc. None of the MRSA strains produced pvl, but up to 30% of S. aureus strains were positive for tst

Staphylococcus aureus Nasal Colonization in Spanish Children. The COSACO Nationwide Surveillance Study

Objective: To assess the prevalence and risk factors for S. aureus and methicillin-resistant S. aureus (MRSA) nasal colonization in Spanish children. Methods: Cross-sectional study of patients <14 years from primary care centers all over Spain. Clinical data and nasal aspirates were collected from March to July 2018. Results: A total of 1876 patients were enrolled. Prevalence of S. aureus and MRSA colonization were 33% (95% CI 30.9-35.1) and 1.44% (95% CI 0.9-2), respectively. Thirty-three percent of the children (633/1876) presented chronic conditions, mainly atopic dermatitis, asthma and/or allergy (524/633). Factors associated with S. aureus colonization were age ≥5 years (OR 1.10, 95% CI 1.07-1.12), male sex (OR 1.43, 95% CI 1.17-1.76), urban setting (OR 1.46, 95% CI 1.08-1.97) and the presence of asthma, atopic dermatitis or allergies (OR 1.25; 95% CI: 1.093-1.43). Rural residence was the only factor associated with MRSA colonization (OR 3.62, 95% CI 1.57-8.36). MRSA was more frequently resistant than methicillin-susceptible S. aureus to ciprofloxacin [41.2% vs 2.6%; p<0.0001], clindamycin [26% vs 16.9%; p=0.39], and mupirocin [14.3% vs 6.7%; p=0.18]. None of the MRSA strains was resistant to tetracycline, fosfomycin, vancomycin or daptomycin. Conclusions: The main risk factors for S. aureus colonization in Spanish children are being above five years of age, male gender, atopic dermatitis, asthma or allergy, and residence in urban areas. MRSA colonization is low, but higher than in other European countries and is associated with rural settings.This study has been supported by The Spanish Ministry of Science and Innovation – Instituto de Salud Carlos III, and Fondos FEDER of the EU, Grant Nº PI18CIII/00372 [Fondo de Investigaciones Sanitarias-Spanish Health Research Fund (ISCIII)]; Grant Award “Jose María Corretger” from the Spanish Society for Pediatric Infectious Diseases; Grant Research Award from the Spanish Association of Pediatric Primary Care; and a Small Grant Award from the European Society for Pediatric Infectious Diseases.S

Characterization of methicillin-resistant Staphylococcus aureus strains colonizing the nostrils of Spanish children

Objective: To characterize the Staphylococcus aureus strains colonizing healthy Spanish children. Methods: Between March and July 2018, 1876 Spanish children younger than 14 years attending primary healthcare centers were recruited from rural and urban areas. Staphylococcus aureus colonization of the anterior nostrils was analyzed. MecA and mecC genes, antibiotic susceptibility, and genotyping according to the spa were determined in all strains, and the following toxins were examined: Panton-Valentine leucocidin (pvl), toxic shock syndrome toxin (tst), and exfoliative toxins (eta, etb, etd). Multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing were performed on methicillin-resistant Staphylococcus aureus (MRSA) strains, as well as pulsed-field gel electrophoresis (PFGE). Results: 619 strains were isolated in 1876 children (33%), and 92% of them were sent for characterization to the Spanish National Centre of Microbiology (n = 572). Twenty (3.5%) of these strains were mecA-positive. Several spa types were detected among MRSA, being t002 the most frequently observed (30%), associating with SCCmec IVc. Among MSSA, 33% were positive for tst, while only 0.73% were positive for pvl. The 20 MRSA strains were negative for pvl, and 6 (30%) harbored the tst gene. Conclusions: methicillin-resistant Staphylococcus aureus nasal colonization in Spanish children is rare, with t002 being the most observed spa type, associated with SCCmec IVc. None of the MRSA strains produced pvl, but up to 30% of S. aureus strains were positive for tst.Sociedad Española Infectologia Pediatrica, Grant/Award Number: José María Corretger. Grant 2018; Spanish Association of Paediatric Primary Care, Grant/Award Number: Grant 2018; European Society for Paediatric Infectious Diseases, Grant/Award Number: Small Grant Award 2018; Instituto de Salud Carlos III, Grant/Award Number: PI18CIII/00372S

Potential role of new molecular plasma signatures on cardiovascular risk stratification in asymptomatic individuals

The evaluation of cardiovascular (CV) risk is based on equations derived from epidemiological data in individuals beyond the limits of middle age such as the Framingham and SCORE risk assessments. Lifetime Risk calculator (QRisk®), estimates CV risk throughout a subjects' lifetime, allowing those. A more aggressive and earlier intervention to be identified and offered protection from the consequences of CV and renal disease. The search for molecular profiles in young people that allow a correct stratification of CV risk would be of great interest to adopt preventive therapeutic measures in individuals at high CV risk. To improve the selection of subjects susceptible to intervention with aged between 30-50 years, we have employed a multiple proteomic strategy to search for new markers of early CV disease or reported CV events and to evaluate their relationship with Lifetime Risk. Blood samples from 71 patients were classified into 3 groups according to their CV risk (healthy, with CV risk factors and with a previously reported CV event subjects) and they were analyzed using a high through quantitative proteomics approach. This strategy allowed three different proteomic signatures to be defined, two of which were related to CV stratification and the third one involved markers of organ damage.This work was supported by grants from the Instituto de Salud Carlos III (PI070537, IF08/3667-1, PI11-02239, PI 14/01917, PI11/01401, PI11/02432, PI13/01873, PI13/01746, PI13/01581, PI14/01650, PI14/01841), PT13/0001/0013, PIE13/00051, PIE13/00045, CP09/00229, CP15/00129, IDC Salud (3371/002), the MutuaMadrileña Foundation, the SENEFRO Foundation and FONDOS FEDER (RD06/0014/1015, RD12/0042/0071). Sociedad Española de cardiología para la Investigación Básica 2017. Grant PRB3 (IPT17/0019 - ISCIII-SGEFI / ERDF. These results are in line with the Spanish initiative on the Human Proteome Project.S

Pseudopterygium: An Algorithm Approach Based on the Current Evidence

Pseudopterygium is a non-progressive conjunctival adhesion to the peripheral cornea secondary to a corneal-limbus damage. According to the literature, the main etiology is a previous eye trauma. Nevertheless, this could be biased by the existence of other underdiagnosed causes of pseudopterygium, some of which may have severe consequences for the integrity of the eye and patient's life. This comprehensive literature review was performed based on a search on the PubMed and Google Scholar databases of relevant pseudopterygium published papers according to our current knowledge and seeks to gather the existing evidence about its diverse etiologies and clinical features, as well as to propose a diagnostic algorithm to simplify its correct approach

Basal oxidation of conserved cysteines modulates cardiac titin stiffness and dynamics

Titin, as the main protein responsible for the passive stiffness of the sarcomere, plays a key role in diastolic function and is a determinant factor in the etiology of heart disease. Titin stiffness depends on unfolding and folding transitions of immunoglobulin-like (Ig) domains of the I-band, and recent studies have shown that oxidative modifications of cryptic cysteines belonging to these Ig domains modulate their mechanical properties in vitro. However, the relevance of this mode of titin mechanical modulation in vivo remains largely unknown. Here, we describe the high evolutionary conservation of titin mechanical cysteines and show that they are remarkably oxidized in murine cardiac tissue. Mass spectrometry analyses indicate a similar landscape of basal oxidation in murine and human myocardium. Monte Carlo simulations illustrate how disulfides and S-thiolations on these cysteines increase the dynamics of the protein at physiological forces, while enabling load- and isoform-dependent regulation of titin stiffness. Our results demonstrate the role of conserved cysteines in the modulation of titin mechanical properties in vivo and point to potential redox-based pathomechanisms in heart disease.This work was supported by the Ministerio de Ciencia e Innovación grants BIO2014-54768-P, BIO2017-83640-P, RYC-2014-16604 to JAC and PGC2018-097019-B-I00 to JV, the Regional Government of Madrid grants S2018/NMT-4443 and PEJ16/MED/TL-1593 to JAC and the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 (PT17/0019/0003- ISCIII-SGEFI /ERDF, ProteoRed), and “la Caixa” Banking Foundation (project code HR17-00247) to JV. We acknowledge funding from the European Research Area Network on Cardiovascular Disease through grant MINOTAUR to SS (The Austrian Science Fund – FWF, I3301) and JAC (ISCIII-AC16/00045). The CNIC is supported by ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and was a Severo Ochoa Center of Excellence (SEV-2015-0505). IMM was the recipient of a CNIC-ACCIONA Masters Fellowship and holds a fellowship from “La Caixa” Foundation (ID 100010434, fellowship code LCF/BQ/DR20/11790009). CSC is the recipient of an FPI-SO predoctoral fellowship BES-2016-076638. We thank Wolfgang A. Linke and Pablo García-Pavía for critical feedback. We are also thankful for the insights of three anonymous reviewers.S