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The PER-2 ß-lactamase is a unique class A enzyme conferring broad spectrum cephalosporin resistance. In this study, we explored the stability of cefiderocol (FDC) against PER-2 ß-lactamase to gain insights into structure activity relationships (SAR) of this synthetic siderophore-conjugated antibiotic. Herein, we show that the MICs of FDC for PER-2 producing isolates and transformants ranged between 0.125 and 64 µg/mL; diazabicyclooctanes (DBOs) reduced the MIC values. In PER-2 mutants, MIC values decreased up to 10-12 dilutions in agreement with previous observations especially in the case of Arg220 substitutions. Catalytic efficiency for PER-2 was 0.072 µM-1 s-1, comparable with PER-1 (0.046 µM-1 s-1) and NDM-1 (0.067 µM-1 s-1). In silico models revealed that FDC within the active site of PER-2 demonstrates unique interactions as a result of the inverted Ω loop fold and extension of the ß3-ß4 connecting loop.
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In Chile, the prevalence of tobacco, alcohol and drug use among adolescents is very high. Decades of research indicate that parenting interventions reduce these risky behaviors. However, there are no parenting interventions validated in Chile to prevent adolescent substance use. This article reports the development of the ¡Vamos por Mas! (¡VxM!) program following the recommendations of the Medical Research Council's framework for designing and evaluating complex interventions. After identifying key intervention components, a preliminary version of a substance-use prevention program was designed. The preliminary intervention targeted families with adolescents in fifth and sixth grade and had four components: personalized feedback, in-person workshops, virtual engagement, and family support, to deliver positive-youth development and family-strengthening content. Then, students, guardians, school staff and community experts from different school systems (N = 111) evaluated the preliminary version of the program through a convergent parallel mixed methods study, including focus groups (N = 14) and surveys (N = 101). In general, all participants had positive perceptions of the program and valued its purpose, strategies, objectives and contents. Suggestions included expanding the purpose to promote healthy relationships, focusing on schools with low and intermediate socioeconomic vulnerability, including self-control content, removing the personalized feedback component and adding two additional components: school partnership and external supervision, among other improvements. With this information, the final version of the ¡VxM! program was developed. After a rigorous intervention development process, the ¡VxM! program is ready to be piloted and evaluated in a randomized trial.
Chile has high rates of tobacco, alcohol and drug use among adolescents. Parenting interventions have shown to reduce these risky behaviors. However, there are no parenting interventions validated in Chile to prevent adolescent substance use. This article reports the development of the ¡Vamos por Mas! (¡VxM!) program to strengthen family relations and prevent adolescent substance use following the recommendations of the Medical Research Council's framework for designing and evaluating complex interventions. In the first phase, key intervention components were identified. Then, a preliminary version of the intervention was designed. In the second phase, perceptions of key stakeholders were collected through focus groups (N = 14) and surveys (N = 101) including adolescents, guardians, school staff and community experts. These participants evaluated the preliminary version of the program and provided feedback. In the final phase of the intervention development process, stakeholder opinions were integrated into the proposal. The final version of the ¡VxM! program included five components: (i) school partnership, (ii) in-person workshops, (iii) virtual engagement, (iv) family support and (v) external supervision. This version is ready to be piloted to evaluate feasibility and preliminary efficacy, before being assessed in a randomized trial.
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Pesquisa Biomédica , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Chile , Etanol , Apoio FamiliarRESUMO
Clenbuterol (Clb) (4-amino-α-[(tert-butylamine) methyl]-3,5-dichlorobenzyl alcohol) is a sympathomimetic agent that exhibits ß2-agonist activity. It is applied as a bronchodilatory, tocolytic, and mucolytic agent and is authorized for clinical management in both human and veterinary therapeutics as a racemic mixture. However, its use is strictly prohibited in animals destined for food production in countries in the European Union and in the United States and Mexico, among many others. The R-(-) enantiomer in clenbuterol stimulates ß2-receptors, whereas the S-(+) enantiomer blocks the effect of ß1-receptors. The aims of this study were to develop a method for detecting and quantifying Clb and its enantiomeric distribution in several bovine tissues. The UHPLC-MS/MS method developed to quantify the target compound at trace levels in these tissues combines high sensitivity with good selectivity and short chromatographic run time. The tissue samples tested were found to contain racemic Clb in concentrations of 5-447 pg g-1 . The enantiomeric analysis of Clb showed that R-(-)-Clb is present at higher concentrations in some tissues, whereas S-(+)-Clb was detected in a ratio of 55/45 in the liver and heart tissues.
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Clembuterol , Humanos , Animais , Bovinos , Clembuterol/análise , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análise , Carne/análise , Fatores de RiscoRESUMO
INTRODUCTION AND AIMS: Substance use is a significant global concern. Strengthening parenting in families with adolescents has been shown to reduce substance use initiation. The ¡Vamos por Más! (¡VxM!) program is a positive-parenting program developed in Chile to improve family relations and reduce adolescent substance use that combines in-person school workshops, multimedia messaging and personalized support. This manuscript reports a mixed-methods evaluation of the pilot implementation of the ¡VxM! program utilizing the Consolidated Framework for Implementation Research and Proctor's taxonomy for process outcomes. METHODS: An explanatory sequential design was used. Quantitative methods evaluated program use, acceptability, appropriateness, and fidelity, and were followed by qualitative focus groups (FGs) to assess the implementation process and understand these outcomes. Thirteen FGs stratified by school and role, including school leaders, program facilitators, participants, and researchers, were conducted. RESULTS: The program was implemented in three schools, reaching 253 families with in-person workshops (40.5% of potential participants), 257 parents who viewed on average 72.1% of sent multimedia messages, and 2 families who used the personalized support (0.3%). Overall, the program was viewed as acceptable and appropriate by participants and implementers due to the high quality of program materials, targeted content, and activities. Implementation differed by schools. Key implementation factors were the outer context, inner school setting, and implementation processes. CONCLUSIONS: This comprehensive evaluation, including both intervention implementers and participants, identified implementation facilitators, barriers, and outcomes. Future ¡VxM! implementations should alter program components of schools with lower engagement to improve program implementation and outcomes.
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Poder Familiar , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Humanos , Avaliação de Programas e Projetos de Saúde , Chile , Promoção da Saúde/métodosRESUMO
OBJECTIVES: Archaeological and genetic research has demonstrated that the Pacific Coast was a key route in the early colonization of South America. Research examining South American skeletons >8000 cal BP has revealed differences in cranial morphology between early and late Holocene populations, which may reflect distinct migration events and/or populations. However, genetic, cultural, and some skeletal data contradict this model. Given these discrepancies, this study examines â¼9000 years of prehistory to test the hypothesis that Early skeletons have a distinct cranial morphology from later skeletons. MATERIALS AND METHODS: Using 3D digital models, craniofacial landmarks, and geometric morphometric analyses, we compared Early Holocene crania (n = 4) to later Chilean samples (n = 90) frequently absent in continental assessments of craniofacial variation. PCA, Mahalanobis distances, posterior and typicality probabilities were used to examine variation. RESULTS: Two of the earliest skeletons from northern Chile show clear affinities to individuals from later sites in the same region. However, the hypothesis cannot be rejected as one Early individual from northern Chile and one individual from inland Patagonia did not always show clear affinities to coastal populations. DISCUSSION: Biological affinities among northern populations and other regions of Chile align with genetic and archaeological data, supporting cultural and biological continuity along the Pacific Coast. In Patagonia, archaeological data are in accordance with skeletal differences between the Early inland steppe individual and coastal populations. This study incorporates 3D methods and skeletal datasets not widely used in assessments of biological affinity, thus contributing to a critical body of research examining the ancient population history of western South America.
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Cefalometria/métodos , Imageamento Tridimensional/métodos , Crânio/anatomia & histologia , Adulto , Antropologia Física , Chile , Feminino , História Antiga , Migração Humana , Humanos , Indígenas Sul-Americanos/história , Masculino , Modelos AnatômicosRESUMO
El tratamiento perioperatorio del paciente programado para cirugía electiva es desafiante debido a las condiciones clínicas que pueden o no estar relacionadas con el procedimiento pendiente. Los médicos de interconsulta, en este caso internista, anestesiólogo, cardiólogo o médico familiar, determinan el riesgo perioperatorio tomando en consideración cualquier complicación inherente al procedimiento quirúrgico, al igual que las comorbilidades relacionadas con la situación aguda actual o con cualquier condición crónica preexistente. En estas circunstancias, debería llevarse a cabo una aproximación sistemática que consiste en la estratificación perioperatoria del riesgo, la optimización del manejo médico y la reducción de las complicaciones. Dicha estratificación está determinada por las comorbilidades propias del paciente y el tipo de procedimiento quirúrgico, mientras que la optimización del manejo médico y la reducción de las complicaciones son determinadas activamente durante la hospitalización. En esta revisión se describen las guías de 2014 del Colegio Americano de Cardiología/Asociación Americana del Corazón, y las guías europeas de Cardiología y Anestesiología (ESC/ESA) del mismo año, considerando un algoritmo de cinco pasos, especialmente en pacientes con enfermedad coronaria conocida o sospechada.
Careful management of the patients undergoing elective surgery is challenging in the perioperative setting because of complex conditions that may or may not be related to the pending surgery. Not only must of the consulting physician like internist, anesthesiologist, cardiologist and family physician take into consideration any complications inherent to the surgical procedure, but they must also consider all related comorbidities plus any previous chronic conditions. In this regard, a careful systematic approach should be undertaken, which consists of: perioperative risk stratification, medical therapy optimization and reduction of complications. Risk stratification is determined by the patient's inherent perioperative cardiac risk factors, whereas medical optimization and diminished complications are actively determined during the hospital course. Our review describes the 2014 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines, and 2014 European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA) guidelines focusing on 5-Step algorithmic approach to managing this clinical problem, particularly for the patient with known or suspected coronary heart disease.
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Anestesia , Cirurgia Geral , Doenças CardiovascularesRESUMO
Las medidas de ejecución funcional o medidas objetivas de ejecución física (MEBE) pueden ser instrumentos útiles para identificar consecuencias adversas de salud en ancianos. Se evaluaron MEBE en ancianos en silla de ruedas de hogares de ancianos y se determinó su asociación con mortalidad y hospitalización 6 meses después. Un total de 25 ancianos mayores de 60 años insti-tucionalizados quienes no tuvieran deterioro cognoscitivo y usuarios de silla de ruedas manual. Se utilizaron las siguientes medidas de evaluación funcional que evaluaban miembros superio-res: alcance funcional, levantamiento del brazo, fuerza de agarre y test de desempeño manual por tiempo (TMP). Se realizó una prueba piloto para adecuar los instrumentos. Los partici-pantes tenían una edad promedio de 74 años, la mitad eran mujeres y 65.4% eran analfabetas. Las patologías más frecuentes fueron fracturas de miembros inferiores (26.9%), enfermedades de medula espinal (26.9%), amputaciones (15.4%), secuelas de ECV (15,4%) y osteoartritis (11.5%). El promedio de las MEBE fueron: Alcance funcional 26.3 cm. (DE 12.5) levantamiento de brazo 8.2 repeticiones (DE 2.6), fuerza de agarre 11.6 kg. (DE 6.9) y el TMP 74.3 puntos (DE 24.3). Las MEBE mostraron una asociación estadísticamente significativa con escalas de valoración de discapaci-dad (Barthel); además, fuerza de agarre y alcance funcional se asociaron con mortalidad a los 6 meses. En conclusión, es posible la adaptación de las MEBE a la población anciana discapacitada en silla de ruedas, son fáciles de ejecutar y exentas de peligro. Además, permiten identificar an-cianos en riesgo y predicen consecuencias adversas de salud.
Performance Based Measures (PBM) have been reported as a predictor of adverse health events in elderly patients. To evaluate the PBM in older adults in nursing homes and long term care (LTC) units using wheelchair and determine their association with related variables. Our secondary objective was to identify morbidity and mortality six months later. A total of 25 adults ageing 60 and older with inclusion criteria: users of manual wheelchair as only mobility device (at least 70% part of their day in wheelchair), no acute diseases affecting mobility at the time of assessment and no cognitive impairment. Four PBM for upper extremities were adapted: Modified Functio-nal Reach (MFR), rise arm (RA), grip strength (GS) and Timed manual performance (TMP). A pilot study was carried out to evaluate the instruments. The participants mean age was 74.1 years (SD 9.2), 52% women and 65.4% illiteracy; the diseases most prevalent were lower limbs fractu-res (26.9%), spinal cord diseases (26.9%), amputations (15.4%), stroke (15,4%), and osteoarthritis (11.5%). The mean of PBM was: Modified Functional Reach 26.3 ( DE 12.5) cm., rise arm 8.2 (SD 2.6) times, grip strength 11.6 (SD 6.9) kg. and TMP 74.3 (SD 24.3) points. Statistical associations were found among PBM and physical disability instrument (Barthel index). GS and MFR were associated with mortality six months later. PBM could be adapted to assess nursing home and LTC manual wheelchair older residents. PBM act as markers of current and future health.
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Humanos , Cadeiras de Rodas , Idoso , Instituição de Longa Permanência para Idosos , ReabilitaçãoRESUMO
The objective of this study was to determine the distribution of staphylococcal cassette chromosome mec (SCCmec) elements in meticillin-resistant coagulase-negative staphylococci (MR-CoNS) isolated from a tertiary-care hospital in Mexico and to examine the relationship to drug resistance. Fifty selected MR-CoNS isolates collected from catheters (n=15), blood (n=15), bone (n=9), bronchial lavage (n=2) and urine (n=2) and one isolate each from an abscess, cerebrospinal fluid, eye, pleural effusion, synovial fluid, tracheal aspirate and wound secretion were examined. Susceptibility testing was performed by the broth microdilution method. SCCmec types were determined by multiplex PCR and PFGE was carried out as described previously for Staphylococcus aureus. Among the MR-CoNS strains studied, the most frequently isolated species were Staphylococcus epidermidis (n=26) and Staphylococcus haemolyticus (n=13). Staphylococcus cohnii (n=5), Staphylococcus hominis (n=3), Staphylococcus sciuri (n=1), Staphylococcus pasteuri (n=1) and the recently described species Staphylococcus pettenkoferi (n=1) were also identified. The most frequent MR-CoNS genotype identified was SCCmec type IVa in S. epidermidis isolates, which also showed a high diversity in their PFGE patterns. A clone was found that amplified both SCCmec III and V elements in five isolates examined. The single MR S. pettenkoferi isolate harboured SCCmec type IVd and the single MR S. pasteuri isolate harboured SCCmec type I. The carriage of SCCmec type III was associated with resistance or intermediate resistance to meropenem (P <0.05). These results confirm the high prevalence of S. epidermidis SCCmec IVa and the high genetic diversity among MR-CoNS strains. As far as is known, this is the first report describing the newly identified S. pettenkoferi possessing SCCmec IVd and S. pasteuri harbouring SCCmec type I. MR-CoNS harbouring SCCmec type III were found to be more resistant to meropenem.
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Coagulase/biossíntese , Variação Genética , Resistência a Meticilina , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cromossomos Bacterianos , Impressões Digitais de DNA , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , México , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Staphylococcus/classificação , Staphylococcus/isolamento & purificação , Adulto JovemRESUMO
El sistema de salud colombiano, la legislación cumple el papel de determinar su estructura y funcionamiento en aras de la garantía de los derechos a la salud y la seguridad social incluidos en la Constitución de 1991. Objetivo: presentar las problemáticas en la formulación e implementación de la legislación del actual sistema, así como las implicaciones sobre sus diferentes actores. Metodología: estudio realizado en seis ciudades colombianas usando la metodología cualitativa de la teoría fundada. Se realizaron 174 entrevistas a médicos, administradores, enfermeras y usuarios. Resultados: los hallazgos evidencian problemas en la formulación e implementación, entre ellos: la sobreproducción y las dificultades para la aprehensión, la influencia de intereses particulares y la no correspondencia de las normas con las necesidades de salud la población. Discusión: estas problemáticas causan barreras de acceso a los servicios de salud y fallos en la calidad de la atención a los pacientes, dilemas éticos e insatisfacción e los profesionales de la salud, así como inestabilidad para las instituciones en los profesionales de la salud. Lo anterior emerge como limitación para la garantía del derecho a la salud y exige un replanteamiento de la legislación a favor de los principios constitucionales y el bienestar colectivo.
In the Colombian health system, the legislation complies with the role of determining its structure and function in order to guarantee the rights to health and social security included in the 1991 Constitution. Objective: to present the issues in the formulation and implementation of legislation in the implications of their various agents. Methodology: a study in six Colombian cities using qualitative methodology based on the theory. 174 interviews were conducted with doctors, administrators nurses and users. Results: the findings reveal problems in the formulation and implementation, including: over-regulation and the difficulties of his apprehension, the influence of special interests and not matching the standards with the needs of the accessing health. Discussion: these problems cause barriers to accessing health services and failures in the quality of patient care, ethical dilemmas and dissatisfaction with health professionals, as well as instability in the health sector institutions. This emerges as a constraint of the law in favor of the constitutional principles and the collective welfare.