Copper(II) complexes of quinoline polyazamacrocyclic scorpiand-type ligands: X-ray, equilibrium and kinetic studies

The formation of Cu(II) complexes with two isomeric quinoline-containing scorpiand-type ligands has been studied. The ligands have a tetraazapyridinophane core appended with an ethylamino tail including 2-quinoline (L1) or 4-quinoline (L2) functionalities. Potentiometric studies indicate the formation of stable CuL2+ species with both ligands, the L1 complex being 3–4 log units more stable than the L2 complex. The crystal structure of [Cu(L1)](ClO4)2·H2O shows that the coordination geometry around the Cu2+ ions is distorted octahedral with significant axial elongation; the four Cu–N distances in the equatorial plane vary from 1.976 to 2.183 Å, while the axial distances are of 2.276 and 2.309 Å. The lower stability of the CuL22+ complex and its capability of forming protonated and hydroxo complexes suggest a penta-dentate coordination of the ligand, in agreement with the type of substitution at the quinoline ring. Kinetic studies on complex formation can be interpreted by considering that initial coordination of L1 and L2 takes place through the nitrogen atom in the quinoline ring. This is followed by coordination of the remaining nitrogen atoms, in a process that is faster in the L1 complex probably because substitution at the quinoline ring facilitates the reorganization. Kinetic studies on complex decomposition provide clear evidence on the occurrence of the molecular motion typical of scorpiands in the case of the L2 complex, for which decomposition starts with a very fast process (sub-millisecond timescale) that involves a shift in the absorption band from 643 to 690 nm

Equilibrium and kinetics studies on bibrachial lariat aza-crown/Cu(II) systems reveal different behavior associated with small changes in the structure

The high-yield synthesis of a new bibrachial lariat azacrown constituted by two tris(2-aminoethyl)amine (tren) units functionalized in one of its arms with a 4-methylquinoline group linked by dimethylene pyridine spacers (L2) is reported for the first time. The speciation studies show formation of mono- and binuclear Cu2+ complexes of similar stability. Comparisons are established with the complexes formed by the precursor tren-quinoline derivative (L4) and with the previously reported ligands containing naphthalene instead of quinoline as the fluorophore (L1, L3). The kinetics of formation and decomposition of Cu2+ complexes with L1 and L2 has been studied. For L1, the acid-promoted decomposition of mono and dinuclear complexes occurs in all cases with a rapid step within the stopped-flow mixing time that leads to the formation of an intermediate that decomposes in two additional steps. In the dinuclear complexes, both metal ions dissociate from the ligand with statistically-controlled kinetics. Complex formation with L1 occurs through the same intermediate observed during the decomposition. For L2, only the formation and decomposition of binuclear complexes could be studied, and the kinetic data show that the metal ion can coordinate both in square pyramidal sp and trigonal bipyramidal (tbp) geometries, coordination being faster in the sp environment and dissociation being faster from tbp. DFT and TD-DFT have been also carried out to determine the geometries with both coordination environments as well as their electronic spectra. The results of calculations indicate that the appearance or not of a mixture of coordination geometries does not necessarily require the participation of the quinoline ring

Equilibrium and kinetic studies on complex formation and decomposition and the movement of Cu2+metal ions within polytopic receptors

Potentiometric studies carried out on the interaction of two tritopic double-scorpiand receptors in which two equivalent 5-(2-aminoethyl)-2,5,8-triaza[9]-(2,6)-pyridinophane moieties are linked with 2,9- dimethylphenanthroline (L1) and 2,6-dimethylpyridine (L2) establish the formation of mono-, bi- and trinuclear Cu2+ complexes. The values of the stability constants and paramagnetic 1H NMR studies permit one to infer the most likely coordination modes of the various complexes formed. Kinetic studies on complex formation and decomposition have also been carried out. Complex formation occurs with polyphasic kinetics for both receptors, although a significant difference is found between both ligands with respect to the relative values of the rate constants for the metal coordination steps and the structural reorganizations following them. Complex decomposition occurs with two separate kinetic steps, the first one being so fast that it occurs within the stopped-flow mixing time, whereas the second one is slow enough to allow kinetic studies using a conventional spectrophotometer. As a whole, the kinetic experiments also provide information about the movement of the metal ion within the receptors. The differences observed between the different receptors can be interpreted in terms of changes in the network of hydrogen bonds formed in the different species

Characterization of a Ferryl Flip in Electronically Tuned Nonheme Complexes. Consequences in Hydrogen Atom Transfer Reactivity

Two oxoiron(IV) isomers (R2a and R2b) of general formula [FeIV(O)(RPyNMe3)(CH3CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4IO4. The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R2a and R2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R2a reacts one order of magnitude faster than R2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand

Characterization of a Ferryl Flip in Electronically Tuned Nonheme Complexes. Consequences in Hydrogen Atom Transfer Reactivity

Two oxoiron(IV) isomers (R2a and R2b) of general formula [FeIV(O)(RPyNMe3)(CH3CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4IO4. The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R2a and R2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R2a reacts one order of magnitude faster than R2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.10 página

Four weeks versus six weeks of ampicillin plus ceftriaxone in Enterococcus faecalis native valve endocarditis: A prospective cohort study

Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.This work was supported in part by the “Fondo de Investigaciones Sanitarias” (FIS) grant 17/01251 from the “Instituto de Salud Carlos III”, Madrid, Spain awarded to JMM. JMM received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19. JMP was member of the Endocarditis Team of the Hospital Clinic of Barcelona, Spain when this project was approved by the GAMES Steering Committee.

Evaluación de los resultados del programa 'Parto en el hospital, comadrona en casa'

Objetivo: Describir las características y la evolución clínica de las puérperas y los neonatos incluidos en un programa de alta precoz hospitalaria. Material y método: Estudio observacional y descriptivo de la población incluida en el programa «Parto en el hospital, comadrona en casa», del Hospital Clínic de Barcelona, desde octubre de 2010 hasta abril de 2013. Resultados: Participaron un total de 150 madres, con una edad (media ± desviación estándar) de 32 ± 4 años. El 70% (n= 105) eran multíparas. Respecto al origen de las participantes, el 57,3% (n= 86) procedían de España, el 24% (n= 36) de Sudamérica y el 13,3% (n= 20) de los países del resto de Europa. Un 95% (n= 137) tenía pareja estable. El 62% (n= 93) tenía estudios superiores. El 55% (n= 82) de los partos fueron con analgesia peridural. El 21% (n= 32) requirió episiotomía o tuvo un desgarro de grado II. El resto no presentó ningún desgarro perineal, o éste fue de grado I. La media de estancia hospitalaria fue de 14 ± 4 horas. El peso de los neonatos al nacer y en el domicilio fue de 3.366 ± 362 y 3.168 ± 344 g, respectivamente. El 96% (n= 144) de las mujeres eligió lactancia materna al alta. En la visita, el 94% (n= 134) continuaba con lactancia exclusiva y el 7,4% (n= 11) presentaba grietas. El 4% (n= 6) de las mujeres y de los neonatos se visitó en urgencias durante el puerperio, y hubo 2 (1,3%) reingresos neonatales, por crisis cianótica e ictericia, respectivamente. Conclusiones: Las mujeres que participaron en el programa eran principalmente españolas, multíparas y con estudios superiores, y en la mitad de los casos optaron por un parto con analgesia peridural. Las dificultades encontradas a las 24 horas tras el alta estaban relacionadas con la lactancia materna, y fue necesaria la determinación precoz de la bilirrubina. El programa facilita el empoderamiento de las familias, sin incrementar la morbilidad materna o del neonato

Physical Fitness Enhancement Through Education, EDUFIT Study: Background, Design, Methodology and Dropout Analysis

El nivel de forma física es un potente indicador del estado de salud cardiovascular ya desde edades tempranas. Mejorar el nivel de condición física es una necesidad educativa ya que contribuye a aumentar la salud pública y el bienestar presente y futuro. El objeto del presente artículo es describir la metodología y diseño de un pro­ yecto educativo diseñado con esta finalidad, denominado EDUFIT (EDUcación para el FITness). EDUFIT se llevó a cabo en 2007 y participaron 67 escolares de 13±1 años, pertenecientes a tres clases de Enseñanza Secundaria. Las clases fueron aleatoriamente asigna­ das a grupo control (GC), grupo experimental 1 (GE1) o grupo expe­ rimental 2 (GE2). El GC recibió 2 sesiones de educación física por semana, el GE1 recibió 4 sesiones (incremento del volumen) y el GE2 recibió 4 sesiones de alta intensidad (incremento del volu­ men+intensidad). Al inicio y tras 16 semanas de intervención se valoró: condición física, composición corporal, perfil lipídico­ metabólico, parámetros ventilatorios, tensión arterial, y rendimiento cognitivo y escolar. La intervención fue viable y tuvo buena acepta­ ción entre el alumnado, padres y centro educativo. Se observaron altas tasas de participación (96%, n=67) y de adhesión al programa (84%, n=56). El análisis de adhesión/abandono mostró que, aunque no llega a ser una diferencia significativa (0,1>P>0,05), los adoles­ centes que completaron el programa mostraron mejores valores en capacidad cognitiva y rendimiento académico, y peores en adiposi­ dad, tensión diastólica, fuerza de prensión manual y presión espira­ toria máxima. La hipótesis del estudio EDUFIT es que duplicar el número de clases de educación física por semana mejorará la condi­ ción física de los adolescentes. Si dicha hipótesis se constata, las implicaciones desde el punto de vista de salud pública podrían ser importantes.Physical fitness is a powerful marker of cardiovascular health already at early stages in life. To promote physical fitness enhancement from the school is therefore needed. The present study describes a school intervention program specifically designed for these purposes, called EDUFIT (EDUcation for FITness). The study was carried out in 2007 and comprised 67 adolescents aged 13+/-1 years from a secondary school who belonged to three different classes. The classes were randomly allocated to control group (CG), experimental group 1 (EG1) and experimental group 2 (EG2). The CG was involved in 2 physical education sessions/week, the EG1 was involved in 4 physical education sessions/week (volume increased) and the EG2 was involved in 4 physical education sessions/week of high intensity (volume+intensity increased). Several health parameters were assessed before and after a 16-weeks intervention: physical fitness, body composition, lipid-metabolic profile, ventilatory parameters, blood pressure, and cognitive and academic performance. The intervention was feasible and well-tolerated. There were high participation and adherence rates, i.e. 96% (n=67) and 84% (n=56) respectively. Yet not always significant (0,1>P>0,05), we observed that the adolescents who satisfactory complete the program showed better cognitive and academic performance, and worse levels of adiposity, diastolic tension, handgrip strength and maximal expiratory pressure. The hypothesis of the EDUFIT study is that to double the number of physical education classes will improve physical fitness in adolescents. The confirmation of the hypothesis could have important public health implications.El presente estudio tiene lugar gracias a recursos materiales y humanos procedentes de dos proyectos europeos financiados por la Comisión Europea: el estudio HELENA (Contract FOOD-CT-2005-007034) y el estudio ALPHA (Ref: 2006120). También gracias a fondos FEDER del Ministerio de Educación y Ciencia (Acciones Complementarias DEP2007-29933-E) y del Grupo de Trabajo 0123/07 del Centro de Profesores y Recursos Murcia II de la Consejería de Educación, Formación y Empleo de la Región de Murcia. Algunos de los investigadores involucrados en este estudio están financiados por becas pre-doctorales y post-doctorales del Ministerio de Educación y Ciencia (AP-2005-3827, AP2005-4358, EX-2007-1124, EX-2008-0641)

Non-specific low back pain in primary care in the Spanish National Health Service: a prospective study on clinical outcomes and determinants of management

BACKGROUND: The Spanish National Health Service is a universal and free health care system. Non-specific low back pain (LBP) is a prevalent disorder, generating large health and social costs. The objectives of this study were to describe its management in primary care, to assess patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months. METHODS: A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians (out of 361 – 20.8%) working in 40 primary care centers in 10 of the 17 administrative regions in Spain, covering 693,026 out of the 40,499,792 inhabitants. Patients were assessed on the day they were recruited, and prospectively followed-up 14 and 60 days later. The principal patient characteristics that were analyzed were: sex, duration of the episode, history of LBP, working status, severity of LBP, leg pain and disability, and results of straight leg raising test. Descriptors of management were: performance of the straight leg raising test, ordering of diagnostic procedures, prescription of drug treatment, referral to physical therapy, rehabilitation or surgery, and granting of sick leave. Regression analysis was used to analyze the relationship between patients' baseline characteristics and physicians' management decisions. Only workers were included in the models on sick leave. RESULTS: Mean age (SD) of included patients was 46.5 (15.5) years, 367 (56.6%) were workers, and 338 (52.5%) were females. Median (25th–75th interquartile range) duration of pain when entering the study was 4 (2–10) days and only 28 patients (4.3%) had chronic low back pain. Diagnostic studies included plain radiographs in 43.1% of patients and CT or MRI scans in 18.8%. Drug medication was prescribed to 91.7% of patients, 19.1% were sent to physical therapy or rehabilitation, and 9.6% were referred to surgery. The main determinants of the clinical management were duration of the episode and, to a lesser extent, the intensity of the pain (especially leg pain), a positive straight leg raising test, and degree of disability. The main determinant of sick leave was the degree of disability, followed by the characteristics of the labor contract and the intensity of leg pain (but not low back pain). After at least 2 months of treatment, 37% of patients were still in pain and approximately 10% of patients had not improved or had worsened. CONCLUSION: Although the use of X-Rays is high, determinants of physicians' management of LBP in primary care made clinical sense and were consistent with patterns suggested by evidence-based recommendations. However, after 2 months of treatment more than one third of patients continued to have back pain and about 10% had worsened