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Texto Alba García Fotografía Luana Failla Text Alba García Photography Luana Failla Boris Buono y Albert cortés, el pasado 2 de junio.Boris Buono and Alberto Cortés, last June 2th. Artista [...]

Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches have been used to obtain photolabile Ru(II) complexes. The two most explored have been the use of monodentate ligands and the incorporation of steric effects between the bidentate ligands and the Ru(II). However, the introduction of electronic effects in the ligands has been less explored. Herein, we report a systematic experimental, theoretical, and photocytotoxicity study of a novel series of Ru(II) complexes Ru1–Ru5of general formula [Ru(phen)2(N∧N′)]2+, where N∧N′ are different minimal strained ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole (BTAT) scaffold, being CH3(Ru1), F (Ru2), CF3(Ru3), NO2(Ru4), and N(CH3)2(Ru5) substituents in the R4 of the phenyl ring. The complexes are stable in solution in the dark, but upon irradiation in water with blue light (λex= 465 nm, 4 mW/cm2) photoejection of the ligand BTAT was observed by HPLC-MS spectrometry and UV–vis spectroscopy, with t1/2ranging from 4.5 to 14.15 min depending of the electronic properties of the corresponding BTAT, being Ru4the less photolabile (the one containing the more electron withdrawing substituent, NO2). The properties of the ground state singlet and excited state triplet of Ru1–Ru5have been explored using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. A mechanism for the photoejection of the BTAT ligand from the Ru complexes, in H2O, is proposed. Phototoxicity studies in A375 and HeLa human cancer cell lines showed that the new Ru BTAT complexes were strongly phototoxic. An enhancement of the emission intensity of HeLa cells treated with Ru5was observed in response to increasing doses of light due to the photoejection of the BTAT ligand. These studies suggest that BTAT could serve as a photocleavable protecting group for the cytotoxic bis-aqua ruthenium warhead [Ru(phen)2(OH2)2]2+.

La pancreatitis aguda constituye uno de los principales motivos de ingreso por causa digestiva. En su manejo resulta crucial un adecuado tratamiento del dolor. Pero apenas existen descripciones sobre las pautas analgésicas empleadas en nuestro medio.

A second-generation series of biscyclometalated 2-(5-aryl-thienyl)-benzimidazole and -benzothiazole Ir(III) dppz complexes [Ir(C^N)2(dppz)]+, Ir1–Ir4, were rationally designed and synthesized, where the aryl group attached to the thienyl ring was p-CF3C6H4or p-Me2NC6H4. These new Ir(III) complexes were assessed as photosensitizers to explore the structure–activity correlations for their potential use in biocompatible anticancer photodynamic therapy. When irradiated with blue light, the complexes exhibited high selective potency across several cancer cell lines predisposed to photodynamic therapy; the benzothiazole derivatives (Ir1and Ir2) were the best performers, Ir2being also activatable with green or red light. Notably, when irradiated, the complexes induced leakage of lysosomal content into the cytoplasm of HeLa cancer cells and induced oncosis-like cell death. The capability of the new Ir complexes to photoinduce cell death in 3D HeLa spheroids has also been demonstrated. The investigated Ir complexes can also catalytically photo-oxidate NADH and photogenerate 1O2and/or •OH in cell-free media.

Despite the approval of several drugs for AML, cytarabine is still widely used as a therapeutic approach. However, 85% of patients show resistance and only 10% overcome the disease. Using RNA-seq and phosphoproteomics, we show that RNA splicing and serine-arginine-rich (SR) proteins phosphorylation were altered during cytarabine resistance. Moreover, phosphorylation of SR proteins at diagnosis were significantly lower in responder than non-responder patients, pointing to their utility to predict response. These changes correlated with altered transcriptomic profiles of SR protein target genes. Notably, splicing inhibitors were therapeutically effective in treating sensitive and resistant AML cells as monotherapy or combination with other approved drugs. H3B-8800 and venetoclax combination showed the best efficacy in vitro, demonstrating synergistic effects in patient samples and no toxicity in healthy hematopoietic progenitors. Our results establish that RNA splicing inhibition, alone or combined with venetoclax, could be useful for the treatment of newly diagnosed or relapsed/refractory AML.

ABSTRACTPeople still drown on beaches in unacceptable numbers due to the lack of knowledge about the risks taking place in them. The proposed methodology forecasts electronic bathing flags in beaches by integrating the benefits of metocean operational systems, machine learning and web-based decision support technologies into a 24/7 risk assessment service that could be easily implemented at any beach worldwide with low costs of maintenance. Firstly, a crosscutting analysis between metocean conditions, beach characteristics and flag records was performed. Secondly, an expert system, based on Deep Learning, was developed to obtain electronic bathing flags as an indicator of the dynamic risk of drowning on beaches. The input variables of the Deep Neural Network were significant wave height, mean wave period, wind velocity, marine current velocity, incidence angle, and beach modal state. Finally, the application of the method to the Santa Catarina’s beaches (Brazil) conveniently reproduced the status flag of beaches.

Puntos para una lectura rápida•Cuando se sospecha un SCA la anamnesis debe incluir las características y el desencadenante de los síntomas, incluido el consumo reciente de cocaína y metanfetamina así como la evaluación de los factores de riesgo cardiovascular.•Debe realizarse un ECG a todo paciente con dolor torácico a menos que exista una causa evidente “no cardiaca”.•Un valor normal seriado de troponina prácticamente excluye una patología cardiaca aguda.•Se recomienda el uso de la ecocardiografía transtorácica como prueba rápida a la cabecera del paciente para establecer la función ventricular, evaluar las posibles anomalías del movimiento de la pared y determinar si hay un derrame pericárdico o patología aórtica.•Los pacientes con alteraciones en el ECG, elevación de hs-cTnI, disfunción sistólica ventricular izquierda aguda o inestabilidad hemodinámica son de alto riesgo y debe de indicarse una coronariografía.•La angio-TAC coronaria se ha convertido en una alternativa no invasiva a la coronariografía.

IntroductionThis pilot study analyzes the effect of a cognitive training program in adults with intellectual disability (ID).MethodTwenty subjects (mean age 52.7 ± 9.77 years) with mild and moderate ID were divided in control and experimental group. Only the experimental group received the training program. This program was applied through the GNPT® (Guttmann, NeuroPersonalTrainer®) platform for people with ID.ResultsThe results revealed a significant improvement in the Kaufman Brief Intelligence Test-2 scores (Matrices subtest) in the experimental group [Z = 2.12; p= .03] after the intervention, indicating an enhancement in fluid ability due to effect of cognitive training program.ConclusionFindings provide evidence of the importance of applying these programs in a systematized way in adults with ID.

Cult actress and fashion muse ROSSY DE PALMA finds inspiration everywhere "For me, reality is a bit hard-core", admits Rossy de Palma, 57. While Almodóvar helped de Palma get her start in the acting world, she now has a prolific portfolio that boasts films with Robert Altman ( I Prêt-à-Porter, i 1994) and Terry Gilliam ( I The Man Who Killed Don Quixote, i 2018), among others. In Almodóvar's most recent release, the Golden Globe - nominated I Parallel Mothers, i de Palma plays Elena, a high-powered magazine editor and the best friend of Janis, a resilient single mother portrayed by Penélope Cruz. [Extracted from the article]

Introduction:The majority of individuals with Down syndrome (DS) show signs of Alzheimer's disease (AD) neuropathology in their fourth decade. However, there is a lack of specific markers for characterizing the disease stages while considering this population's differential features.Methods:Forty-one DS individuals participated in the study, and were classified into three groups according to their clinical status: Alzheimer's disease (AD-DS), mild cognitive impairment (MCI-DS), and controls (CN-DS). We performed an exhaustive neuropsychological evaluation and assessed brain functional connectivity (FC) from magnetoencephalographic recordings.Results:Compared with CN-DS, both MCI-DS and AD-DS showed a pattern of increased FC within the high alpha band. The neuropsychological assessment showed a generalized cognitive impairment, especially affecting mnestic functions, in MCI-DS and, more pronouncedly, in AD-DS.Discussion:These findings might help to characterize the AD-continuum in DS. In addition, they support the role of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD.Impact statementThe pattern of functional connectivity (FC) hypersynchronization found in this study resembles the largely reported Alzheimer's disease (AD) FC evolution pattern in population with typical development. This study supports the hypothesis of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD, and its conclusions could help in the characterization and prediction of Down syndrome individuals with a greater likelihood of converting to dementia.

Bovine pericardium (BP) is a vascular biomaterial used in cardiovascular surgery that is typically cross-linked for masking antigenicity and enhance stability. There is a need for biochemical evaluation of the tissue properties prior to implantation to ensure that quality and reliability standards are met. Here, engineered antigen removed BP (ARBP) that was cross-linked with 0.2% and 0.6% glutaraldehyde (GA), and further calcified in vitro to simulate graft calcifications upon implantation was characterized nondestructively using fluorescence lifetime imaging (FLIm) to identify regions of interest which were then assessed by Raman spectroscopy. We observed that the tissue fluorescence lifetime shortened, and that Raman bands at 856, 935, 1282, and 1682 cm–1decreased, and at 1032 and 1627 cm–1increased with increasing GA cross-linking. Independent classification analysis based on fluorescence lifetime and on Raman spectra discriminated between GA-ARBP and untreated ARBP with an accuracy of 91% and 66%, respectively. Pearson’s correlation analysis showed a strong correlation between pyridinium cross-links measured with high-performance liquid chromatography and fluorescence lifetime measured at 380–400 nm (R= −0.76, p= 0.00094), as well as Raman bands at 856 cm–1for hydroxy-proline (R= −0.68, p= 0.0056) and at 1032 cm–1for hydroxy-pyridinium (R= 0.74, p= 0.0016). Calcified areas of GA cross-linked tissue showed characteristic hydroxyapatite (959 and 1038 cm–1) bands in the Raman spectrum and fluorescence lifetime shortened by 0.4 ns compared to uncalcified regions. FLIm-guided Raman imaging could rapidly identify degrees of cross-linking and detected calcified regions with high chemical specificity, an ability that can be used to monitor tissue engineering processes for applications in regenerative medicine.

Analizar la utilidad del catéter midlineen términos de eficacia y seguridad para tratamientos con una duración superior a 3 días en la población neonatal que precisa ingreso en Unidad de Cuidados Intensivos Neonatales (UCIN).

La escala Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) fue creada para evaluar de forma breve el funcionamiento de las personas con trastorno de desarrollo intelectual y problemas de salud mental/trastornos de conducta. El objetivo del presente trabajo fue estudiar las evidencias sobre la validez de las puntuaciones obtenidas con la escala HoNOS-LD traducida al castellano.

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We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C^N)(N^N)2]OTf (N^N = 2,2′-bipyridine and dipyrido[3,2-d:2′,3′-f]quinoxaline; C^N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiproliferative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.

ABSTRACTIntroduction: The management of lupus nephritis (LN) has changed significantly over the last 10 years due to emerging evidence from large randomised clinical trials that produced good quality data and guided the formulation of two key concepts: the induction of remission and the maintenance phase of immunosuppressive therapy.Areas covered: Optimizing cyclophosphamide and glucocorticoid regimens and the introduction of mycophenolate mofetil for proliferative and membranous LN has been pivotal. Nevertheless, concerns remain about treatment toxicity especially long term glucocorticoid use and exposure to cumulative cyclophosphamide doses. Here we discuss the conventional and newer pharmacological options for managing LN focusing on drug safety and toxicity issues.Expert opinion: The need for effective and less toxic treatments led to the development of the role of targeted biologic therapies in LN. However, evidence from the initial randomized controlled trials has been disappointing, although this reflects inadequate trial design rather than true lack of efficacy.

Coastal lagoon hydrodynamics are strongly influenced by sea water exchange, especially when the connection between the lagoon and the sea is artificially regulated. These situations increase the complexity of the hydrodynamic regime, requiring the use of numerical models to understand their behaviour. Traditionally, one-dimensional models have been used, although in recent years, the development of two-dimensional shallow water models and advanced numerical techniques have increased notably. However, most of the existing bi-dimensional models consider the connection to the sea as a boundary condition, and they do not take into consideration the sea-lagoon exchange. In this paper, a fully two-dimensional hydrodynamic model of a heavily regulated coastal lagoon, which includes the artificial connection with the sea, is presented. The model allows the characterization of water level variation in the lagoon, taking into account the combined effect of different forcings. This model consists of two hydrodynamic modules: a long wave module (two-dimensional depth-averaged) which includes the analysis of a system of sluice gates, and a wind module (quasi three-dimensional). The model was successfully calibrated and validated with real data, showing its ability to accurately describe the hydraulic dynamics of regulated coastal lagoons. [ABSTRACT FROM AUTHOR]

Las determinaciones de cistatina C se han propuesto como nuevo marcador de la función renal y predictor del riesgo cardiovascular en ancianos. Nuestro objetivo fue conocer la prevalencia de individuos con cistatina C elevada en población general y su asociación con factores de riesgo y enfermedad cardiovascular.

No relevant conflicts of interest to declare.

Frequently, depression is a concomitant pathology in anorexia nervosa. To verify this, we carried out a comparative case/control study with 50 anorexic patients, restricting-type (ANP), 50 depressed patients (DP) and 50 non-patients (NP), aged between 13 and 16. We used the Rorschach Test and the Minnesota Multiphasic Personality Inventory (MMPI) and compared the results to parent's observations collected from the Achenbach Child Behavior Checklist (CBCL). Results showed two clearly different groups among participants: ANP with depression (36%) and ANP without depression (64%). This seems to indicate that depression is not a core element in anorexic disorders. However, we also observed a significant increase in the MMPI scale 2, which was probably related to starvation and weight loss. We confirmed the absence of general anxiety in the ANP group and obtained differences between depressive symptoms and those derived from coping deficit disorders. The discussion emphasizes the importance of using several tests to reduce bias in results and conclusions.

Introduction. Despite the recent approval of several drugs for the treatment of AML, the 3 + 7 regimens remain as the standard of care for many patients. Its lack of efficacy represents the main cause of death, since only 10% of patients who show refractoriness/relapse overcome the disease. Therefore, there is still an urgent need for seeking more effective treatments. Aberrant RNA splicing has been described in AML, but its relevance as mechanism of resistance is unclear. In this study, we deepen the mechanism of resistance to cytarabine and the role of splicing factors SR proteins, involved in the spliceosome functionality, to seek more effective therapies for AML.

Integrated genomic analysis including whole genome and RNA sequencing in primary multiple myeloma (MM) cells have reported a universal loss of BCL7A gene in MM patients compared to normal plasma cells (PC). Our Genetic modulation in in-vitro and in-vivo MM models have also validated the loss of BCL7A as an oncogenic event responsible for acquisition of a more proliferative phenotype in MM cells.