ABSTRACT
Many intrinsically disordered proteins contain Gly-rich regions which are generally assumed to be disordered. Such regions often form biomolecular condensates which play essential roles in organizing cellular processes. However, the bases of their formation and stability are still not completely understood. Based on NMR studies of the Gly-rich H. harveyi "snow flea" antifreeze protein, we recently proposed that Gly-rich sequences, such as the third "RGG" region of Fused in Sarcoma (FUS) protein, may adopt polyproline II helices whose association might stabilize condensates. Here, this hypothesis is tested with a polypeptide corresponding to the third RGG region of FUS. NMR spectroscopy and molecular dynamics simulations suggest that significant populations of polyproline II helix are present. These findings are corroborated in a model peptide Ac-RGGYGGRGGWGGRGGY-NH2, where a peak characteristic of polyproline II helix is observed using CD spectroscopy. Its intensity suggests a polyproline II population of 40%. This result is supported by data from FTIR and NMR spectroscopies. In the latter, NOE correlations are observed between the Tyr and Arg, and Arg and Trp side chain hydrogens, confirming that side chains spaced three residues apart are close in space. Taken together, the data are consistent with a polyproline II helix, which is bent to optimize interactions between guanidinium and aromatic moieties, in equilibrium with a statistical coil ensemble. These results lend credence to the hypothesis that Gly-rich segments of disordered proteins may form polyproline II helices which help stabilize biomolecular condensates.
Subject(s)
Glycine/chemistry , Models, Molecular , Peptides/chemistry , Circular Dichroism , Magnetic Resonance Spectroscopy , Protein Structure, SecondaryABSTRACT
OBJETIVOS: Conocer la opinión y describir la actitud ante la adecuación del esfuerzo terapéutico de diferentes profesionales sanitarios. MÉTODO: Estudio multicéntrico, observacional y transversal realizado con enfermeras y médicos que desarrollan su labor asistencial en las unidades de cuidados intensivos pediátricos de cuatro hospitales de la Comunidad de Madrid. Se utilizó un cuestionario de elaboración propia pilotado para valorar su viabilidad y se habilitó una urna clausurada en el control de enfermería para depositarlo en ella. El análisis se realizó con el programa SPPS 21.0. RESULTADOS: El 98,9% de los encuestados declararon estar a favor de la adecuación del esfuerzo terapéutico. Los médicos consideran que la decisión se toma por consenso del equipo multidisciplinar más los padres del niño (48,8%). El 51,1% de las enfermeras opinan que se realiza por consenso de los médicos más los padres y el 65,5% afirman que nunca les consultan en la toma de decisiones de pacientes a su cargo. Al 75% de los médicos siempre o casi siempre les consultan. El 57% de las enfermeras y el 83% de los médicos se sienten capacitados para la toma de decisiones sobre la adecuación del esfuerzo terapéutico. El 77,2% de los profesionales creen que la adecuación se aplica en menos ocasiones de las necesarias. CONCLUSIONES: Existen diferencias entre médicos y enfermeras tanto en la percepción del modelo de toma de decisiones como en el modo de actuación. Los profesionales no siguen ningún protocolo ni circuito de toma de decisiones consensuado
OBJECTIVE: To determine the opinion and describe the attitude of different health professionals on suitability of therapeutic effort. METHOD: Multi-centre, cross-sectional observational study carried out with nurses and doctors who work in the paediatric intensive care units of four hospitals in the Madrid region. A self-administered questionnaire, previously piloted to assess its viability, was used and a sealed box was set up at the nursing station to hand it in. The analysis was performed using SPSS 21.0 software. RESULTS: The 98.9% of the respondents were in favour of suitability of therapeutic effort. Doctors consider that the decision is made with the agreement of the multidisciplinary staff and the child's parents (48.8%). Of the nurses, 51.1% believe that the decision is made by agreement with the doctors and parents. Of the nurses, 65.5% state that they are never asked about decision-making for their patients. Of the doctors, 75% are always or almost always asked. Fifty-seven percent of the nurses and 83% of the doctors feel capable of making decisions about suitability of therapeutic effort. Of the professionals, 77.2% believe that suitability is used less often than required. CONCLUSIONS: There are differences between doctors and nurses both in the perception of the decision-making model and in the way to proceed. Professionals seem not to follow any protocols or circuits in the decision-making process
Subject(s)
Humans , Male , Female , Adult , Attitude of Health Personnel , Intensive Care Units , Terminal Care , Quality of Life , Health Services , Nurses/statistics & numerical data , Physicians/statistics & numerical data , Decision MakingABSTRACT
OBJECTIVE: To determine the opinion and describe the attitude of different health professionals on suitability of therapeutic effort. METHOD: Multi-centre, cross-sectional observational study carried out with nurses and doctors who work in the paediatric intensive care units of four hospitals in the Madrid region. A self-administered questionnaire, previously piloted to assess its viability, was used and a sealed box was set up at the nursing station to hand it in. The analysis was performed using SPSS 21.0 software. RESULTS: The 98.9% of the respondents were in favour of suitability of therapeutic effort. Doctors consider that the decision is made with the agreement of the multidisciplinary staff and the child's parents (48.8%). Of the nurses, 51.1% believe that the decision is made by agreement with the doctors and parents. Of the nurses, 65.5% state that they are never asked about decision-making for their patients. Of the doctors, 75% are always or almost always asked. Fifty-seven percent of the nurses and 83% of the doctors feel capable of making decisions about suitability of therapeutic effort. Of the professionals, 77.2% believe that suitability is used less often than required. CONCLUSIONS: There are differences between doctors and nurses both in the perception of the decision-making model and in the way to proceed. Professionals seem not to follow any protocols or circuits in the decision-making process.
Subject(s)
Attitude of Health Personnel , Clinical Decision-Making , Intensive Care Units, Pediatric , Medical Staff, Hospital , Nursing Staff, Hospital , Adult , Cross-Sectional Studies , Female , Humans , MaleABSTRACT
BACKGROUND: To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism. RESULTS: In 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R2 = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks. CONCLUSION: Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.
ABSTRACT
Las fístulas de paladar suponen una complicación frecuente en la cirugía de los pacientes fisurados. Las opciones de reconstrucción secundaria en fístulas de tamaño moderado-grande son limitadas por la escasez de tejido donante local y las cicatrices de la palatoplastia. Presentamos nuestra experiencia en el tratamiento de fístulas palatinas moderadas-grandes con colgajo músculomucoso basado en la arteria facial (colgajo FAMM: facial artery musculo-mucosal flap) y describimos algunos detalles técnicos que hemos incorporado para mejorar su seguridad.Revisamos 8 pacientes, 5 mujeres y 3 varones, con edades comprendidas entre los 5 y los 18 años, nacidos con fisura palatina que desarrollaron fístulas palatinas tras la palatoplastia primaria y que tras evaluación multidisciplinaria fueron sometidos a reconstrucción con colgajo FAMM. Los tamaños de las fístulas oscilaron entre los 0,5 y los 2,3 cm. de diámetro mayor. El seguimiento postoperatorio de los pacientes fue de 1 a 6 años. Obtuvimos cierre completo de las fístulas de paladar en el primer tiempo quirúrgico y sin complicaciones en 5 casos. Los 2 primeros sufrieron necrosis de los bordes distales del colgajo y precisaron revisión quirúrgica y una paciente sufrió necrosis total que requirió una nueva reconstrucción con colgajo FAMM contralateral. No hemos registrado complicaciones de la zona donante en ninguno de los casos. Consideramos que el colgajo FAMM es una excelente opción para la reparación de fístulas palatinas de tamaño moderadogrande secundarias a fisura palatina congénita, ya que permite aportar una gran cantidad de tejido vascularizado con un arco de rotación amplio, lo que posibilita obtener resultados de obturación satisfactorios. La tasa de complicaciones, tras una curva de aprendizaje relativamente breve, es baja (AU)
Palatal fistulas are a common complication of cleft surgery. Options for secondary reconstruction of moderate to large defects are limited due to the scarcity of local donor tissue as well as the scars from the primary cleft repair. We present our experience in the treatment of moderate to large palatal fistulas with facial artery musculo-mucosal flap (FAMM flap), and we describe some technical details that we have introduced to improve safety. We present 8 patients, 5 female and 3 male, aged 5 to 18 years, with congenital cleft palate who developed moderate to large fistulae that after multidisciplinary evaluation were reconstructed with FAMM flap. The sizes of the fistulae ranged from 0,5 to 2,3 cm. in largest diameter. The follow-up was 1-6 years. We obtained a complete correction of palatal fistula in 5 patients without complications. Marginal necrosis occurred in the first 2 cases and required revision. One patient suffered total flap necrosis and required reconstruction with a contralateral FAMM flap. We did not experience complications of the donor site. We consider this flap an excellent option in moderate to large palatal fistula repair because it allows providing a large amount of well vascularized tissue with a wide arc of rotation. After a relatively short learning curve, complications are rare (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Cleft Palate/surgery , Surgical Flaps , Oral Fistula/surgery , Plastic Surgery Procedures/methods , Myocutaneous Flap , Treatment OutcomeABSTRACT
Introducción. El desarrollo de nuevos biomateriales ha desembocado en la aparición de nuevas prótesis vasculares que mejoren el comportamiento de injertos protésicos de pequeño calibre. Objetivo. El objetivo del presente trabajo es el estudio del comportamiento biológico de prótesis vasculares de poliuretano. Material y métodos. Prótesis: poliuretano-polidimetilsiloxano (PU-PDMS). Caracterización: fragmentos de PU-PDMS se procesaron para su estudio en microscopia óptica y electrónica de barrido. Se determinó la carga eléctrica de la superficie interna mediante análisis espectral. Biocompatibilidad: fragmentos (1 cm2) de PU-PDMS se implantaron en el músculo dorsal de conejos Nueva Zelanda (n= 18) durante 3 y 8 meses. Realizamos estudios morfológicos, inmunohistoquímicos (antiactina) y de reacción de cuerpo extraño (RAM11). Siembra: fragmentos de 1 cm2 se sembraron con células endoteliales de vena umbilical humana. Tiempos de estudio: 24, 48, 72 horas y 7 días. Resultados. La composición es fibrilar, con presencia de numerosos poros. Existencia de cargas negativas en la superficie interna del biomaterial. A los tres meses, la prótesis se embebe en tejido neoformado muy vascularizado y rico en células blancas y células de reacción a cuerpo extraño. A los 8 meses se puede observar la total integración del biomaterial, que aparece rodeado de colágeno y muy vascularizado. A las 24 horas de la siembra observamos una superficie endotelizada, que deja al descubierto grandes poros que se tapizan en los estadios posteriores. Conclusiones. Las prótesis PUPDMS presentan características adecuadas para utilizarse como sustitutos vasculares, gracias a su estructura, ausencia de rechazo y buena integración a corto y medio plazo. (AU)
