Visible light harvesting alkyne hydrosilylation mediated by pincer platinum complexe

In this manuscript we assess the catalytic properties of pincer platinum complexes in alkyne hydrosilylation either under photo or thermal conditions. The visible light-induced hydrosilylation proved to be more efficient. It can be performed at room temperature and required lower catalyst loadings than that operating under thermal conditions. The platinum complexes play a dual role in photohydrosilylation as serve as a photosensitizer and a catalyst enabling species in bond breaking/forming transformations. In addition, alkyne hydrosilylation is achieved with moderate regio- and stereoselectivity but is enhanced under photocatalytic conditions and in the case of terminal alkynes we have observed the formation of β(Z) products not observable under thermal conditions. Such differences in selectivity constitute an example of stereodivergent catalysis dictated under photochemical or thermal conditions. The selectivity differences are ascribed to a distinctive reaction mechanism for the light- vs thermally-induced process that involve radical or organometallic intermediates, respectively.MICIU/AEI/FEDER (PID2021-126071OB-C22 and PID2019-104121GB-I00). Universitat Jaume I (UJI-B2022-23). Generalitat Valenciana (PROMETEU/2020/028).Thanks to PID2021-126071OB-C22 and PID2019-104121GB-I00 funded by MICIN/AEI/10.13039/501100011033/ FEDER “Una manera de hacer Europa”. Generalitat Valenciana (PROMETEU/2020/028) and Universitat Jaume I (UJI-B2022-23). L. I-I. thanks MICIN for grant (FPU20/04385). The authors thank ‘Servei Central d’Instrumentació Científica (SCIC) de la Universitat Jaume I’

Imipenem heteroresistance but not tolerance in Haemophilus influenzae during chronic lung infection associated with chronic obstructive pulmonary disease

Antibiotic resistance is a major Public Health challenge worldwide. Mechanisms other than resistance are described as contributors to therapeutic failure. These include heteroresistance and tolerance, which escape the standardized procedures used for antibiotic treatment decision-making as they do not involve changes in minimal inhibitory concentration (MIC). Haemophilus influenzae causes chronic respiratory infection and is associated with exacerbations suffered by chronic obstructive pulmonary disease (COPD) patients. Although resistance to imipenem is rare in this bacterial species, heteroresistance has been reported, and antibiotic tolerance cannot be excluded. Moreover, development of antibiotic heteroresistance or tolerance during within-host H. influenzae pathoadaptive evolution is currently unknown. In this study, we assessed imipenem resistance, heteroresistance and tolerance in a previously sequenced longitudinal collection of H. influenzae COPD respiratory isolates. The use of Etest, disc diffusion, population analysis profiling, tolerance disc (TD)-test methods, and susceptibility breakpoint criteria when available, showed a significant proportion of imipenem heteroresistance with differences in terms of degree among strains, absence of imipenem tolerance, and no specific trends among serial and clonally related strains could be established. Analysis of allelic variation in the ftsI, acrA, acrB, and acrR genes rendered a panel of polymorphisms only found in heteroresistant strains, but gene expression and genome-wide analyses did not show clear genetic traits linked to heteroresistance. In summary, a significant proportion of imipenem heteroresistance was observed among H. influenzae strains isolated from COPD respiratory samples over time. These data should be useful for making more accurate clinical recommendations to COPD patients

La medicina interna en el ambiente hospitalario

Introducción: los cambios del contexto de trabajo en los hospitales para los internistas exigen perfeccionar el funcionamiento de sus servicios. Objetivos: identificar problemas que afectan a la especialidad Medicina Interna y los cambios organizativos necesarios para su solución, en un hospital clínico-quirúrgico. Material y Métodos: se realizó investigación cualitativa, basada en la actividad de un grupo nominal que dio salida a tareas propias de la dirección estratégica. Resultados: se definió la misión, visión y líneas estratégicas de trabajo del Servicio de Medicina Interna, se caracterizó el contexto y definieron como problemas en orden de prioridad: Deterioro del método clínico; práctica de una Medicina biologicista; insuficiente disponibilidad de camas; limitaciones en los recursos humanos, materiales y financieros para la máxima calidad de la atención y sobrecarga de los servicios clínicos. Se definieron las fortalezas, debilidades, amenazas y oportunidades. De ellas se derivaron propuestas de acciones ofensivas, adaptativas, defensivas y de supervivencia para lograr un cambio positivo en el trabajo de esta especialidad. Conclusiones: la gestión del capital humano en Medicina Interna implica una estructura colaborativa más eficiente para el hospital, que depare mejor utilización de los internistas como médico generalista e integrador, lo que contribuiría a disminuir las fronteras físicas de las salas y centrar el trabajo en los enfermos. Palabras clave: Medicina Interna, dirección estratégica, médico generalista e integrador, estructura colaborativa.</p

Electronic health records and patient registries in medical oncology departments in Spain

We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain. This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM. We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department. Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes. Not applicable The online version contains supplementary material available at 10.1007/s12094-021-02614-9

Innovació i investigació docent per millorar l’enginy i la creativitat dels alumnes d’Enginyeria i Arquitectura

El nou marc de l’EEES i l’experiència docent en las àrees de l’Enginyeria i l’Arquitectura, indueix a pensar en la introducció de noves metodologies docents motivades per la necessitat d’adaptar, en la mesura del possible, els coneixements que l’alumne adquireix a la Universidad al món professional de les empreses. L’ensenyament a Enginyeria i Arquitectura, s’ha ha basat, tradicionalment, en l’aplicació de models matemàtics. Així, els exercicis plantejats als alumnes es redueixen, la majoria de vegades, a aplicar aquest models matemàtics. La realitat professional és ben diferent, l’arquitecte i/o enginyer no tindrà sovint temps de fer anàlisis tant detallats com els que realitzava com alumne; és per això que sembla aconsellable variar el model d’ensenyança / aprenentatge.Peer Reviewe

Deep-Sequencing Reveals Broad Subtype-Specific HCV Resistance Mutations Associated with Treatment Failure

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions.Ministerio de Economía y Empresa; IDI-20151125Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-

Imipenem heteroresistance but not tolerance in Haemophilus influenzae during chronic lung infection associated with chronic obstructive pulmonary disease

Antibiotic resistance is a major Public Health challenge worldwide. Mechanisms other than resistance are described as contributors to therapeutic failure. These include heteroresistance and tolerance, which escape the standardized procedures used for antibiotic treatment decision-making as they do not involve changes in minimal inhibitory concentration (MIC). Haemophilus influenzae causes chronic respiratory infection and is associated with exacerbations suffered by chronic obstructive pulmonary disease (COPD) patients. Although resistance to imipenem is rare in this bacterial species, heteroresistance has been reported, and antibiotic tolerance cannot be excluded. Moreover, development of antibiotic heteroresistance or tolerance during within-host H. influenzae pathoadaptive evolution is currently unknown. In this study, we assessed imipenem resistance, heteroresistance and tolerance in a previously sequenced longitudinal collection of H. influenzae COPD respiratory isolates. The use of Etest, disc diffusion, population analysis profiling, tolerance disc (TD)-test methods, and susceptibility breakpoint criteria when available, showed a significant proportion of imipenem heteroresistance with differences in terms of degree among strains, absence of imipenem tolerance, and no specific trends among serial and clonally related strains could be established. Analysis of allelic variation in the ftsI, acrA, acrB, and acrR genes rendered a panel of polymorphisms only found in heteroresistant strains, but gene expression and genome-wide analyses did not show clear genetic traits linked to heteroresistance. In summary, a significant proportion of imipenem heteroresistance was observed among H. influenzae strains isolated from COPD respiratory samples over time. These data should be useful for making more accurate clinical recommendations to COPD patients

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P &lt; 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P &lt; 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P &lt; 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P &lt; 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Cyclometallated platinum compounds: optical and biological applications

Programa de Doctorat en Química Orgànica[eng] This Doctoral Thesis is focused on the synthesis of cyclometallated platinum compounds with different structural modifications rationally designed specifically for biological or optical applications. Specifically, tridentate [C,N,N’] and [N,C,N] cyclometallated compounds have been synthesised, differing in their oxidation state, the nature of the cyclometallated ligand, with variations in the rigidity and aromaticity, and with a variety of ancillary ligands. Several synthetic methodologies have been employed and the correct formation of the compounds has been checked by a great variety of techniques such as NMR and infrared spectroscopy, mass spectrometry elemental analysis and single crystal X-ray diffraction. Concerning biological applications, several compounds with anticancer properties have been successfully synthesised, obtaining some species with a high efficacy and minimal toxicity studied through cell viability assays. Additionally, several of the designed compounds presented a complete absence of cross-resistance and thanks to additional testing such as cyclic voltammetry, DNA interaction studies and cell-cycle phase distribution experiments, it has been observed that they present mechanisms of action not analogous to those of the clinically approved drugs. Concerning optical applications, the tuning of the structure of the compounds, especially in the cyclometallating ligands, has been key to achieve efficient phosphorescent platinum(II) compounds with various emissive states. Both emission quantum yields and lifetimes have been determined and DFT calculations have allowed a further understanding of the molecules excited states. Additionally, modification of the ancillary ligands, the solvent, the concentration or the presence of an additional metallic cation have been used as a strategy to promote a red-shift in the emission through the formation of aggregates or heterometallic compounds. Finally, one compound has been selected and tested for the preparation of a Light-Emitting Electrochemical Cell (LEEC) obtaining novel results for a platinum-doped device which are competitive with those reported in the literature for other metals and, to the best of our knowledge, the most efficient platinum system used for LEEC applications.[cat] Aquesta Tesi Doctoral està centrada en la síntesi de compostos ciclometal·lats de platí amb diferents modificacions estructurals dissenyades racionalment per dur a terme aplicacions biològiques o òptiques. Específicament, s’han sintetitzat compostos ciclometal·lats tridentats [C,N,N’] i [N,C,N] que es diferencien en el seu estat d’oxidació, naturalesa del lligand ciclometal·lat, amb variacions en la rigidesa i l’aromaticitat, i amb una varietat de lligands auxiliars. S’han utilitzat diferents metodologies sintètiques i s’ha comprovat la correcta formació dels compostos amb una gran varietat de tècniques com l’espectroscòpia RMN i infraroja, l’espectrometria de masses, l’anàlisi elemental i la difracció de raigs-X de monocristall. Quant a les aplicacions biològiques, s’han sintetitzat amb èxit diversos compostos amb propietats anticancerígenes, obtenint algunes espècies amb eficàcia elevada i amb toxicitat mínima que han estat estudiades a través d’assajos de viabilitat en cèl·lules. A més, diversos compostos dels que s’han sintetitzat van presentar una absència completa de resistència entrecreuada i gràcies a proves addicionals com la voltametria cíclica, estudis de la interacció amb l’ADN i experiments de distribució a les fases del cicle cel·lular, s’ha observat que presenten mecanismes no anàlegs als dels fàrmacs clínicament aprovats. Quant a les aplicacions òptiques, l’afinació de l’estructura dels compostos, especialment en el lligand ciclometal·lat, ha estat clau per aconseguir compostos de platí(II) amb una fosforescència eficient i amb diversos estats emissius. S’han determinat els rendiments quàntics i temps de vida d’emissió i els càlculs DFT han permès un coneixement més detallat dels estats excitats de les molècules. A més, la modificació dels lligands auxiliars, el dissolvent, la concentració o la presència d’un catió metàl·lic addicional, s’han utilitzat com a estratègia per promoure un desplaçament cap al vermell en l’emissió a través de la formació d’agregats o compostos heterometàl·lics. Finalment, s’ha seleccionat un compost per la preparació de cel·les electroquímiques emissores de llum (LEECs) obtenint nous resultats per un dispositiu dopat amb platí que són competitius amb els resultats descrits a la bibliografia per altres metalls i, dins del nostre coneixement, el sistema de platí més eficient utilitzat per la seva aplicació en LEECs