ABSTRACT
A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.
Subject(s)
Antitubercular Agents , Quantitative Structure-Activity Relationship , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Molecular Structure , Drug Design , Databases, FactualABSTRACT
Bulky iron complexes are described that catalyze the site-selective oxidation of alkyl C-H bonds with hydrogen peroxide under mild conditions. Steric bulk at the iron center is introduced by appending trialkylsilyl groups at the meta-position of the pyridines in tetradentate aminopyridine ligands, and this effect translates into high product yields, an enhanced preferential oxidation of secondary over tertiary C-H bonds, and the ability to perform site-selective oxidation of methylenic sites in terpenoid and steroidal substrates. Unprecedented site selective oxidation at C6 and C12 methylenic sites in steroidal substrates is shown to be governed by the chirality of the catalysts.
Subject(s)
Iron/chemistry , Steroids/chemistry , Carbon/chemistry , Catalysis , Coordination Complexes/chemistry , Hydrogen/chemistry , Hydrogen Peroxide/chemistry , Ligands , Oxidation-Reduction , StereoisomerismABSTRACT
Selective oxidation of alkyl C-H groups constitutes one of the highest challenges in organic synthesis. In this work, we show that mononuclear iron coordination complexes Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-BPBPP)] (Δ-2P) catalyze the fast, efficient, and selective oxidation of nonactivated alkyl C-H groups employing H(2)O(2) as terminal oxidant. These complexes are based on tetradentate N-based ligands and contain iron centers embedded in highly structured coordination sites defined by two bulky 4,5-pinenopyridine donor ligands, a chiral diamine ligand backbone, and chirality at the metal (Λ or Δ). X-ray diffraction analysis shows that in Λ-1P and Λ-2P the pinene rings create cavity-like structures that isolate the iron site. The efficiency and regioselectivity in catalytic C-H oxidation reactions of these structurally rich complexes has been compared with those of Λ-[Fe(CF(3)SO(3))(2)((S,S)-MCP)] (Λ-1), Λ-[Fe(CF(3)SO(3))(2)((S,S)-BPBP)] (Λ-2), Δ-[Fe(CF(3)SO(3))(2)((R,R)-BPBP)] (Δ-2), Λ-[Fe(CH(3)CN)(2)((S,S)-BPBP)](SbF(6))(2) (Λ-2SbF(6)), and Δ-[Fe(CH(3)CN)(2)((R,R)-BPBP)](SbF(6))(2) (Δ-2SbF(6)), which lack the steric bulk introduced by the pinene rings. Cavity-containing complexes Λ-1P and Λ-2P exhibit enhanced activity in comparison with Δ-1P, Δ-2P, Λ-1, Λ-2, and Λ-2SbF(6). The regioselectivity exhibited by catalysts Λ-1P, Λ-2P, Δ-1P, and Δ-2P in the C-H oxidation of simple organic molecules can be predicted on the basis of the innate properties of the distinct C-H groups of the substrate. However, in specific complex organic molecules where oxidation of multiple C-H sites is competitive, the highly elaborate structure of the catalysts allows modulation of C-H regioselectivity between the oxidation of tertiary and secondary C-H groups and also among multiple methylene sites, providing oxidation products in synthetically valuable yields. These selectivities complement those accomplished with structurally simpler oxidants, including non-heme iron catalysts Λ-2 and Λ-2SbF(6).
ABSTRACT
The Integrated Health Area "Barcelona Esquerra" (Área Integral de Salud de Barcelona Esquerra - AIS-BE), which covers a population of 524,000 residents in Barcelona city, is running a project to improve healthcare quality and efficiency based on co-ordination between the different suppliers in its area through the participation of their professionals. Endowed with an Organisational Model that seeks decision-taking that starts out from clinical knowledge and from Information Systems tools that facilitate this co-ordination (an interoperability platform and a website) it presents important results in its structured programmes that have been implemented such as the Reorganisation of Emergency Care, Screening for Colorectal Cancer, the Onset of type 2 Diabetes Mellitus, Teledermatology and the Development of Cross-sectional Healthcare Policies for Care in Chronicity.
ABSTRACT
No disponible
Subject(s)
Humans , Primary Health Care , Referral and Consultation/statistics & numerical data , Eye Health ServicesABSTRACT
BACKGROUND: Despite well established clinical guidelines, performance of long-term oxygen therapy (LTOT) programs shows marked variability among territories. The current study assessed the LTOT program and the health status of patients on LTOT prior to the deployment of community-based integrated care in an urban health district of Barcelona (Spain). AIMS: To assess: i) the LTOT program and health status of the patients on LTOT in the health district; ii) their frailty profile; and, iii) the requirements for effective deployment of integrated care services for these patients. METHODS: Cross-sectional observational study design including all patients (n = 406) on LTOT living in the health district. Health status, frailty, arterial blood gases, forced spirometry and hand-grip muscle strength were measured. Network analysis of frailty was carried out. RESULTS: Adequacy of LTOT prescription (n = 362): 47% and 31% of the patients had PaO2 ≤ 60 mmHg and ≤55 mmHg, respectively. Adherence to LTOT: 31% of all patients used LTOT ≥15 h/d; this figure increased to 67% in those with PaO2≤60 mmHg. Assessment of frailty: Overall, LTOT patients presented moderate to severe frailty. Care complexity was observed in 42% of the patients. CONCLUSIONS: Adequacy and adherence to LTOT was poor and many patients were frail and complex. The outcomes of the network analysis may contribute to enhance assessment of frailty in LTOT patients. These observations suggest that an integrated care strategy has the potential to improve the health outcomes of these patients.
Subject(s)
Oxygen Inhalation Therapy , Pulmonary Disease, Chronic Obstructive , Aged , Aged, 80 and over , Blood Gas Analysis/methods , Cross-Sectional Studies , Delivery of Health Care, Integrated/methods , Delivery of Health Care, Integrated/statistics & numerical data , Female , Health Services Needs and Demand , Health Status Disparities , Humans , Long-Term Care/methods , Long-Term Care/statistics & numerical data , Male , Middle Aged , Oxygen Inhalation Therapy/adverse effects , Oxygen Inhalation Therapy/methods , Oxygen Inhalation Therapy/statistics & numerical data , Program Evaluation , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy , Spain/epidemiology , Spirometry/methods , TimeABSTRACT
Fast, efficient, and highly stereoselective epoxidation with H2O2 is reached by manganese coordination complexes with e-rich aminopyridine tetradentate ligands. It is shown that the electronic properties of these catalysts vary systematically with the stereoselectivity of the O-atom transfer event and exert fine control over the activation of hydrogen peroxide, reducing the amount of carboxylic acid co-catalyst necessary for efficient operation.
Subject(s)
Aminopyridines/chemistry , Epoxy Compounds/chemical synthesis , Hydrogen Peroxide/chemistry , Manganese/chemistry , Organometallic Compounds/chemistry , Catalysis , Crystallography, X-Ray , Electrons , Epoxy Compounds/chemistry , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
No disponible
Subject(s)
Humans , Chilaiditi Syndrome/diagnosis , Subphrenic Abscess/diagnosis , Diagnosis, Differential , Risk FactorsABSTRACT
INTRODUCTION AND OBJECTIVES: To assess the impact of a program integrating cardiology and primary care in clinical practice, compared with usual care. The integrated care consists of a hospital cardiologist in each primary care clinic, shared clinical history, joint practice guidelines, consultation sessions, and other coordinating tools. METHODS: Observational, cross-sectional study of 2 series of chronic outpatients: conventional and integrated care. We analyzed patient distribution and the impact on good clinical practice indicators in patients with ischemic heart disease, heart failure and atrial fibrillation, along with primary care practitioner satisfaction and use of resources. RESULTS: We included 3194 patients (1572 usual care, 1622 integrated care). Integrated care changed the patient distribution, allowing the cardiologist to focus on serious pathologies while cardiovascular risk factors and stable patients were monitored in primary care. In ischemic heart disease, improvement was observed in cholesterol management and blood pressure control; optimal medical treatment was more frequently prescribed and ventricular function evaluated more often. In heart failure, ß-blockers treatment increased and functional class was assessed more often. In atrial fibrillation, an increase in anticoagulation prescription and echocardiography evaluation was observed. Satisfaction parameters improved with integrated care. The use of resources was not increased. CONCLUSIONS: Using our integration model, follow-up and chronic treatment of patients with ischemic heart disease, heart failure, and atrial fibrillation were improved. Monitoring of chronic patients was redistributed between primary care and cardiology, and family physicians' satisfaction levels improved. There was no increase in use of resources. Full English text available from: www.revespcardiol.org.
Subject(s)
Cardiology/trends , Delivery of Health Care, Integrated/trends , Heart Diseases/therapy , Primary Health Care/trends , Aged , Atrial Fibrillation/therapy , Attitude of Health Personnel , Data Collection , Delivery of Health Care, Integrated/standards , Electrocardiography , Female , Guideline Adherence/statistics & numerical data , Health Resources/statistics & numerical data , Heart Failure/therapy , Humans , Long-Term Care , Male , Myocardial Ischemia/therapy , Practice Guidelines as Topic , Referral and ConsultationABSTRACT
No disponible
Subject(s)
Humans , Male , Poland Syndrome/diagnosis , Pectoralis Muscles/abnormalities , Mesoderm/abnormalitiesABSTRACT
No disponible
Subject(s)
Humans , Female , Middle Aged , Agranulocytosis/diagnosis , Agranulocytosis/drug therapy , Agranulocytosis/chemically induced , Dipyrone/adverse effects , Anti-Bacterial Agents/therapeutic useABSTRACT
A simple and straightforward methodology toward the synthesis of novel 2,6-disubstituted-4-alkoxypyrimidine derivatives of type 16 and 19 has been developed. This methodology, initially developed in solution, can be perfectly adapted to the solid support under analogous conditions, taking full advantage of automated parallel synthesis systems. This successful methodology benefits from the key role played by the thioether linkage placed at the 2-position in 3, 9, or 13 in a double manner: on one side, the steric effect exerted by the thioether linkage is likely to be responsible for the very high observed selectivity toward the formation of the O-alkylation products. On the other side, this sulfur linkage can serve not only as a robust point of attachment for the heterocycle, stable to a number of reaction conditions, but also as a means of introducing a new element of diversity through activation to the corresponding sulfone (safety-catch linker concept) and subsequent ipso-substitution reaction with a variety of different N-nucleophiles.
ABSTRACT
Introducción y objetivos. Evaluar el impacto de un programa de integración entre cardiología y atención primaria en la práctica clínica, comparado con la atención convencional. La integración consiste en un cardiólogo hospitalario en cada centro de atención primaria, historia clínica común, guías clínicas consensuadas, sesiones de consultoría y otras herramientas de coordinación. Métodos. Estudio observacional de dos muestras transversales sobre prevalencias en periodos antes y después de la intervención: atención convencional y atención integrada. Se analiza: distribución de pacientes atendidos, impacto en indicadores de buena práctica clínica en los pacientes con cardiopatía isquémica, insuficiencia cardiaca y fibrilación auricular, satisfacción de atención primaria y uso de recursos. Resultados. Se incluyó a 3.194 pacientes (1.572 en atención convencional y 1.622 en integrada). La integración redistribuyó a los pacientes y aumentó el control del cardiólogo sobre enfermedades graves y el control desde primaria de los factores de riesgo y pacientes estables. En cardiopatía isquémica, mejoró el control de colesterolemia, presión arterial, optimización del tratamiento y documentación de la función ventricular. En insuficiencia cardiaca, aumentó el tratamiento con bloqueadores beta y la valoración funcional. En fibrilación auricular, mejoró el estudio con ecocardiografía e indicación de anticoagulación. El uso de recursos no aumentó. La satisfacción de los médicos de primaria se incrementó con la integración. Conclusiones. Tras la integración, mejoró el control y el tratamiento crónico de los pacientes con cardiopatía isquémica, insuficiencia cardiaca y fibrilación auricular, se redistribuyó a los pacientes crónicos entre atención primaria y cardiología, y aumentó la satisfacción de los médicos de familia, sin objetivarse incremento en el uso de recursos (AU)
Introduction and objectives. To assess the impact of a program integrating cardiology and primary care in clinical practice, compared with usual care. The integrated care consists of a hospital cardiologist in each primary care clinic, shared clinical history, joint practice guidelines, consultation sessions, and other coordinating tools. Methods. Observational, cross-sectional study of 2 series of chronic outpatients: conventional and integrated care. We analyzed patient distribution and the impact on good clinical practice indicators in patients with ischemic heart disease, heart failure and atrial fibrillation, along with primary care practitioner satisfaction and use of resources. Results. We included 3194 patients (1572 usual care, 1622 integrated care). Integrated care changed the patient distribution, allowing the cardiologist to focus on serious pathologies while cardiovascular risk factors and stable patients were monitored in primary care. In ischemic heart disease, improvement was observed in cholesterol management and blood pressure control; optimal medical treatment was more frequently prescribed and ventricular function evaluated more often. In heart failure, Beta-blockers treatment increased and functional class was assessed more often. In atrial fibrillation, an increase in anticoagulation prescription and echocardiography evaluation was observed. Satisfaction parameters improved with integrated care. The use of resources was not increased. Conclusions. Using our integration model, follow-up and chronic treatment of patients with ischemic heart disease, heart failure, and atrial fibrillation were improved. Monitoring of chronic patients was redistributed between primary care and cardiology, and family physicians¡¯ satisfaction levels improved. There was no increase in use of resources (AU)