Marcadores ecocardiograficos de ventrículo derecho como factores predictores de displasia broncopulmonar en recién nacidos prematuros de muy bajo peso

Los avances en la medicina perinatal han permitido que la mortalidad asociada a la prematuridad se haya reducido desde mediados de siglo XX. Sin embargo, la incidencia de comorbilidades como la displasia broncopulmonar (DBP) no ha disminuido de forma paralela a pesar de los grandes esfuerzos que la comunidad científica ha realizado para establecer algún tratamiento o estrategia postnatal eficaz para minimizar su impacto. La DBP es la enfermedad pulmonar crónica del recién nacido prematuro (RNPT) debida a la disrupción del normal desarrollo pulmonar. Es la complicación más frecuente y quizás la más grave del RNPT y lleva consigo no solo una mayor morbimortalidad respiratoria si no un mayor riesgo de retraso en el neurodesarrollo. Aunque se han investigado múltiples marcadores predictores de DBP a nivel clínico, bioquímico y de imagen, aún no existe ninguno que sea capaz de identificar de manera precoz que RNPT tendrán más riesgo de desarrollarla y puedan beneficiarse de medidas preventivas precoces. En el desarrollo de la DBP existe tanto una afectación parenquimatosa como vascular pulmonar. Partiendo de la hipótesis de que la enfermedad vascular pulmonar concomitante influiría en la normal maduración del miocardio derecho, propusimos como objetivo principal de esta tesis identificar marcadores de función del ventrículo derecho que se modifiquen de manera precoz en aquellos RNPT menores de 32 semanas de gestación (SG) y 1500 gramos que desarrollaran DBP. Para ello llevamos a cabo un estudio de cohorte prospectiva que incluyó a recién nacidos prematuros de muy bajo peso al nacer (RNPTMBP) ingresados en nuestra UCIN durante el periodo 2015-2017. En una fase inicial del estudio, se analizó la variabilidad intra e interobservador en la realización de las ecocardiografías, utilizando el doppler tisular (TDI) y TAPSE. Concluimos que tanto TAPSE como las medidas derivadas de TDI son suficientemente reproducible en RNPTMBP. Tras el periodo de reclutamiento, se incluyeron un total de 101 pacientes en los que se analizó la función del ventrículo derecho de manera seriada mediante la determinación de NTproBNP plasmático y la realizaron de ecocardiografías utilizando el doppler tisular y el TAPSE. Los niveles de NTproBNP fueron diferentes entre los que desarrollaban DBP y los que no desde los 14 días de vida, manteniéndose esta diferencia significativa hasta los 35 días de vida. Calculamos un punto de corte óptimo de 2.264 pg/mL a los 14 días (S100%, E 86% y área bajo la curva de 0,93). Al analizar las ecocardiografías seriadas se observó que TAPSE, E', A' y S' aumentaron con el tiempo mientras que MPI-TDI fue disminuyendo. La edad gestacional al nacer y la edad postmenstrual influyeron en estos parámetros, evolucionando de distinta manera en aquellos que desarrollarían DBP. Los distintos parámetros ecocardiográficos sumados a los niveles de NTproBNP a los 14 días de vida se asociaron con el posterior desarrollo de DBP en distintos modelos predictivos. Conclusión: La evaluación miocárdica de los RNPTMBP mediante el uso combinado del NTproBNP y la ecocardiografía nos ayudaría a identificar a aquellos RNPTMBP con mayor riesgo de desarrollar formas moderadas o graves de DBP y posibles candidatos a estrategias preventivas

Myocardial Function Maturation in Very-Low-Birth-Weight Infants and Development of Bronchopulmonary Dysplasia

Background: Myocardial function in very-low-birth-weight infants (VLBWIs) develops during early postnatal life, but different patterns of temporal evolution that might be related to the development of bronchopulmonary dysplasia (BPD) are not completely understood. Methods: A prospective cohort study including VLBWIs admitted to our NICU from January 2015 to 2017 was conducted. Plasma N-terminal pro B type natriuretic peptide (NTproBNP) levels were measured, and echocardiograms were performed at 24 and 72 h of life and weekly thereafter until 36 weeks of postmenstrual age (PMA). We measured the tricuspid annular plane systolic excursion (TAPSE) by M-mode; the lateral tricuspid E', A', and S' waves; and the myocardial performance index (MPI) by tissue doppler imaging (TDI). The subjects were divided into non-BPD and BPD groups. Results: We included 101 VLBWIs. The TAPSE and E', A', and S' waves increased while MPI-TDI decreased over time. Birth gestational age (GA) and postnatal PMA impacted these parameters, which evolved differently in those who developed BPD compared to those in the non-BPD group. The NTproBNP levels at 14 days of life and different echocardiographic parameters were associated with the development of BPD in different multivariate models. Conclusion: TAPSE and TDI values depend on GA and PMA and follow a different temporal evolution that is related to the later development of BPD. Combined biochemical and echocardiographic biomarkers can help identify which VLBWIs are at higher risk of developing BDP

Two-Dimensional Self-Assembly Driven by Intermolecular Hydrogen Bonding in Benzodi-7-azaindole Molecules on Au(111)

1. Introduction ARTICLE SECTIONSJump To Molecular organization has a critical effect on the physical, chemical, and biological properties of organic materials with applications in areas as diverse as electronics, photonics, catalysis, or biomedicine. (1−5) In fact, the control of matter and processes at the nanoscale represents the essence of nanotechnology. (6) Nevertheless, concerning the arrangement of organic materials, since the structure of molecular solids is governed by very weak noncovalent interactions, it is currently very difficult to set a reliable structure–property correlation that can predict the organization in the solid state from the structure of the molecule. (7−9) With the aim of gaining a better understanding of the subtle energy balance that leads to a certain molecular organization, great efforts have been made in the design of molecules that can be used as models to be studied in the areas of crystal engineering. (10,11) These circumstances that have been extensively addressed in 3D structures are equally applicable and have lately received much attention concerning the 2D molecular ordering on surfaces. (12−14) In this case, apart from the molecule–molecule interactions, the confinement into a two-dimensional environment implies that the molecule–substrate interactions, controlling the organic material physisorption, become an indispensable aspect to be considered in the structural characterization. (15) One of the approaches that can contribute to a better control of the molecular organization is the supramolecular self-assembly. (16−18) In this regard, hydrogen bonding becomes a useful tool due to the higher energy and directionality of hydrogen bonds when compared to other noncovalent interactions. (19) Thus, the strategic location of hydrogen bonding sites in a molecule can be used to control the thermodynamics of intermolecular interactions, partially influencing the growth of molecular nanostructures through a bottom-up approach. (20−22) Focusing our attention on conjugated molecules, which have gained much relevance due to their use as semiconductors in different electronic applications (organic field-effect transistors, organic light-emitting devices, or organic and hybrid solar cells), their charge transport properties are determined by their intermolecular interactions and their disposition at the substrate interface. (23−25) Therefore, the characterization of the molecular arrangement on surfaces provides essential information for the interpretation of material properties and for the development of novel materials. (26−28) Scanning tunneling microscopy (STM) becomes a particularly valuable technique for the study of self-assembled nanostructures on surfaces, given the degree of detail that can be reached with molecular or atomic resolution. (29,30) In this regard, it is worth highlighting the results reported for hydrogen-bonded conjugated systems with application in the area of organic electronics. Quinacridone has been comprehensively studied on different surfaces such as highly oriented pyrolytic graphite (HOPG), Ag(111), Ag(100), and Cu(111). (31−33) Although different degrees of strength in the adsorption of quinacridone have been observed depending on the molecule–substrate interactions, in all cases, homochiral linear structures were observed for each of the expected surface enantiomers. This arrangement results from the complementary hydrogen bonds set between the carbonyl and the NH groups present in the structure of quinacridone. Similar results were reported for the surface self-assembly of indigo on Cu(111), where enantiopure one-dimensional chains were observed. (34) Diketopyrrolopyrrole (DPP) is another building block frequently used in the synthesis of organic semiconductors. Its structure also contains two carbonyl groups and two NHs representing the same hydrogen bonding motif as quinacridone and indigo. The short conjugation length of DPP can be easily enlarged by attaching aromatic substituents. These derivatives form hydrogen-bonded linear structures intercalated with solvent molecules when deposited from long alkanoic acid solutions on HOPG. (35,36) The N-heteroacene dihydrotetraazapentacene constitutes another conjugated molecule whose ability to self-assemble on Au(111), Cu(110), and c-plane sapphire surfaces has been studied. (37−39) In this case, the N–H···N interactions between tetrahydropyrazine and pyrazine-like nitrogens induce the formation of well-ordered molecular rows that grow in homochiral domains. Within this context, we have recently reported a supramolecular approach based on the surface self-assembly of a conjugated tripodal system that formed expanded enantiopure domains. (40) The self-resolution resulting from the formation of energetically favored hydrogen-bonded hexamers led to a two-dimensional framework. The reciprocal hydrogen bonding set through strategically located 7-azaindole units has revealed its suitability as a building block for controlling the molecular disposition of conjugated systems as we have demonstrated in different electronic applications. (41,42) Accordingly, herein we report the integration of this building block into a structurally related molecule, namely, benzodi-7-azaindole (BDAI), resulting from the condensation of two 7-azaindole units to a central benzene core (Figure 1). This system reinforces the hydrogen bonding by using a stronger base as an acceptor site (Npyridine···H-Npyrrole) and differs from most of the previously reported molecules based on C═O···HN interactions. Moreover, the fused 7-azaindole building block leads to fully conjugated systems that contrast the cross-conjugation commonly observed in most of the abovementioned compounds. Figure 1 Figure 1. Structure of 6,12-dihydrobenzo[1,2-b:4,5-b’]di(7-azaindole), BDAI. HBD: hydrogen bond donor site; HBA: hydrogen bond acceptor site. The surface chirality emerging from the adsorption of this molecule with a centrosymmetric structure can produce two surface enantiomers when deposited on Au(111). Ideally, the molecules can form extended unidirectional hydrogen-bonded structures. Besides, the lateral packing of these structures leads to expanded domains with either brick-wall or herringbone arrangement depending on the homochiral or racemic composition, respectively. In this work, we use several surface-science experimental techniques, including STM, high resolution X-ray photoelectron spectroscopy (HR-XPS), and near-edge X-ray absorption fine structure spectroscopy (NEXAFS), combined with density functional theory (DFT) calculations, to get detailed characterization of the geometry and bonding of self-assembled 2D monolayers of BDAI molecules on Au(111), in ultrahigh vacuum (UHV), as well as their thermal stability. The chosen substrate Au(111) provides a weak substrate–molecule interaction and allows the observation of molecular structures close to a free-standing situation. 2. Experimental Section ARTICLE SECTIONSJump To The synthesis of 6,12-dihydrobenzo[1,2-b:4,5-b’]di(7-azaindole), BDAI, has been reported elsewhere. (43) The preparation and characterization of physisorbed layers have been performed in two different UHV systems: a home-laboratory with STM, low energy electron diffraction (LEED), quadrupole mass spectrometry (QMS), and Auger electron spectroscopy (AES) techniques, and a synchrotron laboratory for HR-XPS and NEXAFS. 2.1. Scanning Tunneling Microscopy (STM) A gold surface was prepared by sputtering and annealing cycles of a Au(111) single crystal. Cleanliness was checked by AES and LEED using a for-grid SPECTALEED from Omicron. Pre-purified BDAI molecules were evaporated in UHV from a tantalum crucible, and the evaporation rates were measured using a quartz balance. Typically, low evaporation rates about 0.1 Å/min were used while monitoring the process via a quadrupolar mass spectrometer (QMS). The sample prepared was transferred to the STM chamber. The images were obtained using an Omicron VT-STM operated with Nanotec’s WSxM (44) software and electronics. STM images were acquired at several temperatures in a range between room temperature and 50 K without substantial differences. STM tips used were made of electrochemical etched W wire, pre-cleaned by annealing in vacuum and self-sputtering processes. (45) 2.2. High-Resolution X-ray Photoelectron Spectroscopy (HR-XPS) and Near-Edge X-ray Absorption Fine Structure (NEXAFS) The HR-XPS and NEXAFS experiments were performed at the ALOISA beamline, at Elettra synchrotron. (46) For the HR-XPS and NEXAFS measurements, the deposition rate was checked during deposition with a quartz crystal microbalance. The typical deposition rate was 0.1 Å/min for monolayer films and 0.4 Å/min for multilayer ones. The monolayer coverage (ML) was found to correspond to an effective thickness of 2.5 Å, as determined from the residual XPS intensity after thermal desorption of a multilayer. The C and N K-edge spectra were taken in electron yield mode using a channeltron detector, (46) and they were further analyzed following the procedure described in the literature. (47) The orientation of the surface with respect to the linear polarization of the synchrotron beam was changed by rotating the sample around the beam axis while keeping a constant grazing angle of 6°. This scattering geometry allows the change from linear p-polarization (light polarization perpendicular to the sample surface) to linear s-polarization (light polarization parallel to the sample surface) without any variation of the illuminated area on the sample. The photoemission spectra were taken with the X-ray beam impinging on the sample at a grazing incidence angle (4°) at two photon energies, namely, 400 and 515 eV, to measure the XPS core levels Au 4f, C 1s, and N 1s. The binding energy (BE) scale was calibrated with respect to the Au 4f7/2 substrate peak at 84.00 eV. The background due to inelastically scattered photoelectrons has been subtracted from raw data by a Shirley background routine, the convolution of a Gaussian and a Lorentzian function has been used to fit the photoemission peaks, and more details about the fitting procedure are given in the SI. During the synchrotron measurements, to minimize the beam-induced damage, the sample was continuously displaced. The Au(111) surface was prepared by standard sputtering and annealing procedures. The cleanliness of the surface before deposition was checked by AES and HR-XPS. 2.3. Computational Details On the basis of the experimental LEED and STM evidences, the structure, electronic properties, and theoretical STM imaging of the two different BDAI molecular phases on Au(111) observed have been theoretically investigated by density functional theory (DFT) by the use of an adequate combination of the plane-wave and localized basis set DFT-based atomistic simulation packages QUANTUM ESPRESSO (48) and FIREBALL (49) (see further details in the SI). To make a direct comparison with the XPS experimental results for the different phases, calculation of N 1s core level binding energy shifts (CLS) has been performed with the plane-wave code QUANTUM ESPRESSO (48) within the final state approximation (50) (see the Supporting Information). 3. Results and Discussion ARTICLE SECTIONSJump To 3.1. STM and Computational Results The first evidence of the formation of ordered assemblies of BDAI on gold is obtained by LEED. Extra spots, in registry with the Au(111) LEED reflections, appear in the pattern after submonolayer evaporation of BDAI, as it is shown in the inset of Figure 2a. STM images, recorded at this particular molecular coverage, show ordered structures (Figure 2a) arranged in quasi-one-dimensional molecular rows. Centrosymmetric BDAI molecules become chiral when deposited flat on a surface. Given the restrictions imposed by the impossibility of surface flipping, depending on the face of the molecule that gets physisorbed, two possible surface enantiomers originate. The observed rows are ascribed to one of these enantiomers. The reciprocal N–H···N interactions between neighboring molecules induce a chiral selectivity allowing only the precise enantiomer to form a whole row of molecules with the same chirality. These rows became the structural unit of the BDAI self-assembling (Figure 2d) and grow preferentially following the gold reconstruction lines (Figure S1 in the Supporting Information), namely, along the [112̅] directions. An increase in coverage produces a further packing of the homochiral rows, with hydrogen bonding between adjacent molecules, extending laterally the assembly. The formation of enantiopure domains has been typically observed for other centrosymmetric molecules whose hydrogen bonding on the surface has been characterized. (33,38) Interestingly, the particularities of the BDAI structure, with a pseudolinear skeleton and the hydrogen bonding sites located at both ends of the polyheteroaromatic system, lead to a self-assembled structure with a noticeable intermolecular shift within the supramolecular rows. As a consequence, these rows can adopt two different molecular arrangements distinguishable in the STM images: the brick-wall packing (Figure 2b) and the herringbone packing (Figure 2c). The brick-wall domains correspond to hydrogen-bonded rows constituted by molecules with the same surface chirality (Figure 2b,e) that we assigned to the R enantiomer (marked in blue in Figure 2e). Figure 2e exemplifies the domain that we assigned to the R enantiomer (highlighted in blue). Differently, the herringbone domains are formed by homochiral hydrogen-bonded rows that are alternated with rows of the opposite surface chirality, producing an extended racemic coverage (Figure 2c,f), with R and L enantiomers (rotated rightward or leftward, respectively, with respect to the direction of the gold reconstruction line). Figure 2 Figure 2. (a) STM image of the quasi-one-dimensional rows (120 × 120) nm2. The inset shows the LEED pattern at E = 21.3 eV. (b) STM images (10 × 10) nm2 of brick-wall packing and (c) herringbone packing of the BDAI molecule at a constant-current regime (Itunnel = 50 nA and Vbias = 100 mV). (d) Formation of the order unit, a chain of homochiral molecules, through N–H···N bonds. (e) Homochiral and (f) racemic pictorial top views of both DFT fully structurally optimized molecular phases, with R and L enantiomers marked in blue and red, respectively. The unit cell obtained for the brick-wall arrangement is (1.06 × 2.09) nm2 with an angle of 99°, while in the herringbone arrangement, the unit cell is (1.75 × 2.22) nm2 with an angle of 106°. In the latter packing, some rows of molecules are narrower, probably due to electronic effects. In both domains, intermolecular stabilization of the adlayers is mainly driven by complementary donor–acceptor N–H···N hydrogen bonds between adjacent molecules in the rows (with average N···N distances of 2.95 and 2.85 Å for the brick-wall packing and herringbone phases, respectively). Additionally, different edge-to-edge intermolecular interactions (with distances ranging between 2.2 and 2.6 Å) contribute to the lateral packing of homochiral or enantiomer rows producing densely packed domains in both phases. Figure 2e,f shows the DFT results corresponding to the full structural optimization of these molecular domains. Resulting interfaces reveal very close molecular arrangements as compared with the experimental STM images, fully consistent with the representative distances extracted from them. In both phases, the interaction between the molecular adlayer and the Au(111) substrate has an eminent van der Waals character, with no subtle chemistry underlying (computed molecule/substrate charge transfer < 0.05e–). The interaction with the substrate in this physisorption regime is intense enough to anchor the molecules to the surface but not sufficient to distort the gas-phase molecular morphology, which has its reflection in that the molecules of both phases are essentially flat on the surface (vide infra for NEXAFS discussion) at perpendicular distances of 3.19 and 3.32 Å and binding energies per molecule of −1.12 and −0.93 eV for the brick-wall and herringbone molecular arrangements, respectively. Binding energies have been obtained as the difference between the computed total energy of the whole interfacial systems and the sum of the total energies of the corresponding surfaces and molecular adlayers separately. This slight difference of 0.19 eV in the adsorption energies between both phases seems to arise from a more efficient packing of the brick-wall arrangement, which also manifests in the lower adsorption energy and a slightly lower adsorption molecular distance. The less robust packing of the herringbone adlayer favors a slightly lower decoupling degree from the substrate with respect to the brick-wall phase, thus decreasing the binding energy with the Au surface. Experimentally, in a rough analysis of the STM images, we also observe a preference for the brick-wall phase with around 67% of the covered areas, even though this homochiral structure requires segregation of the enantiomers. We have also simulated theoretical STM images based on the Keldish–Green formalism for the optimized interfacial models obtained under the constant-current regime as in the experiments. Excellent match between the experimental and simulated images has been obtained for both structures: brick-wall (Figure 3a) and herringbone (Figure 3b). The superposition of the structural adlayer models onto the simulated STM images allows the assignment of a molecule to each individual protrusion observed in the STM images. Intramolecular resolution is slightly higher in the simulated images than in the experimental ones since simulations are performed at 0 K without considering the effect of the environmental thermal bath, whereas STM images were recorded at 100 K. Figure 3 Figure 3. BDAI simulated STM images (a) of the brick-wall phase and (b) of the herringbone arrangement. The insets show the experimental STM images. 3.2. HR-XPS Results The spectroscopic characterization of almost one physisorbed monolayer (0.8 ML or 2.0 Å) was carried out by HR-XPS probing both C 1s and N 1s levels (Figure 4). The N 1s core level for 0.8 ML of BDAI fitted with three components at binding energies of 398.35, 399.13, and 399.85 eV (Figure 4a); details of the fit are found in Table S1 of the Supporting Information. The areas of the more intense peaks are 43 and 53%, respectively, showing reasonable agreement, within the experimental error, with the presence of two non-equivalent N atoms in the molecule. The difference in energy between the main features is 0.78 eV, which matches the experimental value of 0.8 eV, found in the literature for the 2,3-dihydro-7-azaindole molecule in gas phase. (51) The peak at 398.35 eV corresponds to N-pyridine as it has been previously reported in the literature at 398.00 eV, (52) while the second peak is ascribed to the pyrrolic NH whose binding energy has been reported at about 400 eV. (52−54) The decrease in the binding energy of this component with respect to the reported value, about 0.87 eV, is due to the formation of the intermolecular hydrogen bond. This interaction affects the polarization of the covalent N–H bond, producing a lower binding energy shift on the N 1s level with respect to the isolated molecule. For the same reason, the nitrogen atom in the pyridine ring experiences a shift to higher binding energies of 0.35 eV. Shifts in the binding energy of N acceptor atoms due to the formation of new hydrogen bonds have been previously reported in the literature. (55,56) Figure 4 Figure 4. (a) N 1s and (b) C 1s XPS spectra for 0.8 ML of the BDAI molecule. Carbon and nitrogen atoms have been labeled according to their bond connectivity for the interpretation of XPS spectra. The small component located at 399.85 eV can be attributed to (−NH) that does not form H bonds or hydrogenated pyridine. (53) Concerning the C 1s core level for the 0.8 ML on Au(111), the deconvolution of the spectra fitted well with three components located at 284.06, 284.74, and 285.70 eV with 52, 35, and 13% of relative weight, respectively (Figure 4b). The molecule presents eight nonequivalent carbon atoms, and, although it is not possible to solve the contribution of each C atom to the spectra, they can be grouped according to their interatomic connectivity. In agreement with these criteria, the C atoms bonded to C or H (type C and D) are ascribed to the peak with a lower binding energy (theoretically 63% of the total area), the C atoms bonded to one N atom (type E and F) are attributed to the second component (theoretically 25% of the total area), and finally, the C atoms bonded to two more electronegative N atoms (type G) correspond to the higher binding energy component (theoretically 13% of the total area). The areas of each component are in agreement with the different kinds of C atoms present in the molecule. Theoretical DFT-based calculations of N 1s CLS have been carried out to rationalize the origin of the N 1s core level differences observed in the XPS experiments (Figure 5). The binding energy difference between N atoms in the pyridine and pyrrole rings has been computed for the two optimized BDAI/Au brick-wall (Figure 5b) and herringbone (Figure 5c) interfacial phases. Figure 5 Figure 5. Pictorial view of the DFT-optimized systems considered for the calculations of the N 1s CLS. (a) Gas-phase BDAI, where the N atoms are not involved in any intermolecular bond and are taken as reference (Nref1 and Nref2). Trial systems: (b) brick-wall interfacial phase and (c) herringbone interfacial phase. N atoms of intere

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Lung ultrasound score has better diagnostic ability than NT-proBNP to predict moderate-severe bronchopulmonary dysplasia.

The N-terminal end of B-type natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) score have been proven to be adequate early biomarkers of bronchopulmonary dysplasia (BPD) in preterm infants. Our aim was to study if the predictive capacity of each one is increased by analyzing them together. We included infants born before 32 weeks with NT-proBNP and LUS scores on the first day of life (DOL) and on the 3rd, 7th, and 14th DOL and compared the diagnostic ability for moderate-severe BPD (msBPD) of each biomarker and in combination. We also compared them with a multivariate model of msBPD using only clinical variables. The sample size was 133 patients, and twenty-seven (20%) developed msBPD. The LUS score on the 7th DOL had better performance than NT-proBNP at the same moment: area under the receiver operating characteristic curve (AUC) 0.83 (0.75-0.89) versus 0.66 (0.56-0.75), p = 0.003, without differences in the rest of the times studied. These values did not increase when using the combination of both. A multivariate regression model that included only clinical variables (birth weight and invasive mechanical ventilation (IMV) at the 7th DOL) predicted msBPD with the same AUC as after the addition of any of these biomarkers, neither together. The LUS score is a better predictor of msBPD on the 7th DOL than NT-proBNP in preterm infants born before 32 weeks, although they have similar diagnostic accuracy on the 1st, 3rd, and 14th DOL. Neither of them, nor together, have a better AUC for msBPD than a clinical model with birthweight and the need for IMV at the 7th DOL. • NT-proBNP and LUS score are early predictors of moderate-severe bronchopulmonary dysplasia (msBPD). • The combination of both NT-proBNP and LUS score does not increase the predictive ability of each separately

Synthesis and Two‐Dimensional Chiral Surface Self‐Assembly of a π‐Conjugated System with Three‐Fold Symmetry: Benzotri(7‐Azaindole)

The synthesis of a novel expanded π-conjugated system, namely benzotri(7-azaindole), BTAI, is reported. Its C3h symmetry along with the integration of six complementary donor and acceptor N−H⋅⋅⋅N hydrogen bonds in the conjugated structure promote the 2D self-assembly on Au(111) over extended areas. Besides, a perfect commensurability with the gold lattice endows the physisorbed molecular film with a remarkable stability. The structural features of BTAI result in two levels of surface chirality: Firstly, the molecules become chiral upon adsorption on the surface. Then, due to the favorable N−H⋅⋅⋅N hydrogen bond-directed self-assembly, along with the relative molecular rotation with respect to the substrate, supramolecular chirality manifests in two mirror enantiomorphous domains. Thus, the system undergoes spontaneous chiral resolution. LEED and STM assisted by theoretical simulations have been employed to characterize in detail these novel 2D conglomerates with relevant chiral properties for systems with C3h symmetry.Fil: Rodriguez, Luis Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche; Argentina. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Gómez, Paula. Universidad de Murcia; EspañaFil: Más Montoya, Miriam. Universidad de Murcia; EspañaFil: Abad, José. Universidad Politécnica de Cartagena; EspañaFil: Tárraga, Alberto. Universidad de Murcia; EspañaFil: Cerdá, Jorge I.. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Méndez, Javier. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Curiel, David. Universidad de Murcia; Españ

Synthesis and Two-Dimensional Chiral Surface Self-Assembly of a π-Conjugated System with Three-Fold Symmetry: Benzotri(7-Azaindole)

The synthesis of a novel expanded π-conjugated system, namely benzotri(7-azaindole), BTAI, is reported. Its C3h symmetry along with the integration of six complementary donor and acceptor N−H⋅⋅⋅N hydrogen bonds in the conjugated structure promote the 2D self-assembly on Au(111) over extended areas. Besides, a perfect commensurability with the gold lattice endows the physisorbed molecular film with a remarkable stability. The structural features of BTAI result in two levels of surface chirality: Firstly, the molecules become chiral upon adsorption on the surface. Then, due to the favorable N−H⋅⋅⋅N hydrogen bond-directed self-assembly, along with the relative molecular rotation with respect to the substrate, supramolecular chirality manifests in two mirror enantiomorphous domains. Thus, the system undergoes spontaneous chiral resolution. LEED and STM assisted by theoretical simulations have been employed to characterize in detail these novel 2D conglomerates with relevant chiral properties for systems with C3h symmetry.Fil: Rodriguez, Luis Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Bariloche; Argentina. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Gómez, Paula. Universidad de Murcia; EspañaFil: Más Montoya, Miriam. Universidad de Murcia; EspañaFil: Abad, José. Universidad Politécnica de Cartagena; EspañaFil: Tárraga, Alberto. Universidad de Murcia; EspañaFil: Cerdá, Jorge I.. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Méndez, Javier. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Curiel, David. Universidad de Murcia; Españ