Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat

Comportamiento de hormigón confinado con FRP en pilares cuadrados

A significant amount of research has been conducted on FRP-confined circular columns, but much less is known about rectangular/square columns in which the effectiveness of confinement is much reduced. This paper presents the results of experimental investigations on low strength square concrete columns confined with FRP. Axial compression tests were performed on ten intermediate size columns. The tests results indicate that FRP composites can significantly improve the bearing capacity and ductility of square section reinforced concrete columns with rounded corners. The strength enhancement ratio is greater the lower the concrete strength and also increases with the stiffness of the jacket. The confined concrete behaviour was predicted according to the more accepted theoretical models and compared with experimental results. There are two key parameters which critically influence the fitting of the models: the strain efficiency factor and the effect of confinement in non-circular sections.La mayoría de las investigaciones sobre hormigón confinado con FRP se han realizado sobre pilares de sección circular, pero el comportamiento en secciones cuadradas/rectangulares, donde el confinamiento es menos eficaz, es mucho menos conocido. Este trabajo presenta los resultados de un estudio experimental sobre probetas de hormigón de baja resistencia y sección cuadrada. Se han ensayado a compresión centrada diez probetas de tamaño intermedio. Los resultados indican que el confinamiento mejora significativamente la resistencia y ductilidad del hormigón en columnas de sección cuadrada con las esquinas redondeadas. El incremento de resistencia es mayor cuanto menor es la resistencia del hormigón sin confinar y también aumenta con la rigidez del encamisado. Los resultados se compararon con los obtenidos según los modelos teóricos más aceptados. Hay dos parámetros críticos en el ajuste de los modelos: el factor de eficiencia de la deformación y el efecto de confinamiento en secciones no circulares

Percepciones de los pacientes con enfermedades reumáticas tratados con biológicos subcutáneos sobre su nivel de información. encuesta RHEU-LIFE

[Abstract] Objective: To investigate, in Spanish patients with rheumatic diseases treated with subcutaneous biological drugs, their sources of information, which sources they consider most relevant, and their satisfaction with the information received in the hospital. Methods: Rheumatologists from 50 hospitals handed out an anonymous survey to 20 consecutive patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis treated with subcutaneous biologicals. The survey was developed ad hoc by 4 rheumatologists and 3 patients, and included questions with closed-ended responses on sources of information and satisfaction. Results: The survey was handed-out to 1,000 patients, 592 of whom completed it (response rate: 59.2%). The rheumatologist was mentioned as the most important source of information (75%), followed by the primary care physician, nurses, and electronic resources; 45.2% received oral and written information about the biological, 46.1% oral only, and 6.0% written only; 8.7% stated that they had not been taught to inject the biological. The percentage of patients satisfied with the information received was high (87.2%), although the satisfaction was lower in relation to safety. If the information came from the rheumatologist, the satisfaction was higher (89.6%) than when coming from other sources (59.6%; P<.001). Satisfaction was also higher if the information was provided orally and written (92.8%) than if provided only orally (86.1%; P=.013); 45.2% reported having sought information from sources outside the hospital. Conclusions: The rheumatologist is key in transmitting satisfactory information on biological treatment to patients. He or she must also act as a guide, since a high percentage of patients seeks information in other different sources.[Resumen] Objetivo. Conocer las fuentes de las que los pacientes españoles con enfermedades reumáticas tratados con fármacos biológicos subcutáneos obtienen información, cuáles consideran más relevantes y su satisfacción con la información recibida en el hospital. Métodos. Reumatólogos de 50 hospitales entregaron una encuesta anónima, desarrollada ad hoc por 4 reumatólogos y 3 pacientes, a 20 pacientes consecutivos con artritis reumatoide, espondiloartritis axial o artritis psoriásica tratados con biológicos subcutáneos. La encuesta incluyó preguntas con respuestas cerradas sobre los aspectos mencionados previamente. Resultados. Recibieron la encuesta 1.000 pacientes, 592 la devolvieron cumplimentada (tasa de respuesta: 59,2%). El reumatólogo fue mencionado como la fuente de información más importante (75%), seguido del médico de atención primaria, la enfermería y los recursos electrónicos. El 45,2% recibió información oral y por escrito sobre el biológico, el 46,1% solo oral, el 6% solo por escrito. Un 8,7% declaró no haber sido enseñado a inyectarse el biológico. El porcentaje de pacientes satisfechos con la información recibida fue elevado (87,2%), aunque la satisfacción fue menor en temas relacionados con la seguridad. Si la información provenía del reumatólogo, la satisfacción era mayor (89,6%) que cuando provenía de otras vías (59,6%; p < 0,001). La satisfacción también era mayor si se dio oral y por escrito (92,8%) frente a solo oral (86,1%; p = 0,013). Un 45,2% declaró haber buscado información en fuentes fuera del hospital. Conclusiones. El reumatólogo es clave a la hora de transmitir información satisfactoria al paciente en tratamiento biológico. Debe además actuar de guía, ya que un elevado porcentaje busca información en fuentes distintas

Perceptions of patients with rheumatic diseases on the impact on daily life and satisfaction with their medications: RHEU-LIFE, a survey to patients treated with subcutaneous biological products

[Abstract] Objective: The aim of this study was to explore perceptions of patients with rheumatic diseases treated with subcutaneous (SC) biological drugs on the impact on daily life and satisfaction with current therapy, including preferred attributes. Methods: A survey was developed ad hoc by four rheumatologists and three patients, including Likert questions on the impact of disease and treatment on daily life and preferred attributes of treatment. Rheumatologists from 50 participating centers were instructed to handout the survey to 20 consecutive patients with rheumatoid arthritis (RA), axial spondyloarthritis (ax-SpA), or psoriatic arthritis (PsA) receiving SC biological drugs. Patients responded to the survey at home and sent it to a central facility by prepaid mail. Results: A total of 592 patients returned the survey (response rate: 59.2%), 51.4% of whom had RA, 23.8% had ax-SpA, and 19.6% had PsA. Patients reported moderate-to-severe impact of their disease on their quality of life (QoL) (51.9%), work/daily activities (49.2%), emotional well-being (41.0%), personal relationships (26.0%), and close relatives’ life (32.3%); 30%–50% patients reported seldom/never being inquired about these aspects by their rheumatologists. Treatment attributes ranked as most important were the normalization of QoL (43.6%) and the relief from symptoms (35.2%). The satisfaction with their current antirheumatic therapy was high (>80% were “satisfied” or “very satisfied”), despite moderate/severe impact of disease. Conclusion: Patients with rheumatic diseases on SC biological therapy perceive a high disease impact on different aspects of daily life, despite being highly satisfied with their treatment; the perception is that physicians do not frequently address personal problems. Normalization of QoL is the most important attribute of therapies to patients

Behaviour of FRP confined concrete in square columns

A significant amount of research has been conducted on FRP-confined circular columns, but much less is known about rectangular/square columns in which the effectiveness of confinement is much reduced. This paper presents the results of experimental investigations on low strength square concrete columns confined with FRP. Axial compression tests were performed on ten intermediate size columns. The tests results indicate that FRP composites can significantly improve the bearing capacity and ductility of square section reinforced concrete columns with rounded corners. The strength enhancement ratio is greater the lower the concrete strength and also increases with the stiffness of the jacket. The confined concrete behaviour was predicted according to the more accepted theoretical models and compared with experimental results. There are two key parameters which critically influence the fitting of the models: the strain efficiency factor and the effect of confinement in non-circular sections.La mayoría de las investigaciones sobre hormigón confinado con FRP se han realizado sobre pilares de sección circular, pero el comportamiento en secciones cuadradas/rectangulares, donde el confinamiento es menos eficaz, es mucho menos conocido. Este trabajo presenta los resultados de un estudio experimental sobre probetas de hormigón de baja resistencia y sección cuadrada. Se han ensayado a compresión centrada diez probetas de tamaño intermedio. Los resultados indican que el confinamiento mejora significativamente la resistencia y ductilidad del hormigón en columnas de sección cuadrada con las esquinas redondeadas. El incremento de resistencia es mayor cuanto menor es la resistencia del hormigón sin confinar y también aumenta con la rigidez del encamisado. Los resultados se compararon con los obtenidos según los modelos teóricos más aceptados. Hay dos parámetros críticos en el ajuste de los modelos: el factor de eficiencia de la deformación y el efecto de confinamiento en secciones no circulares

Plan nacional de investigación en comunicación agropecuaria.

Fromula las actividades de investigación que se propone realizar la División de Comunicación del ICA, a corto y mediano plazo, con el objeto de apoyar la transferencia de tecnología a los productores del país. Figuran proyectos de investigación con grandes productores, con existentes técnicos particulares, con instituciones con agentes de cambio y con pequeños productores. Incluye información sobre la programación y presupuesto para la ejecución del pla

KASCADE-Grande Limits on the Isotropic Diffuse Gamma-Ray Flux between 100 TeV and 1 EeV

KASCADE and KASCADE-Grande were multi-detector installations to measure individual air showers of cosmic rays at ultra-high energy. Based on data sets measured by KASCADE and KASCADE-Grande, 90% C.L. upper limits to the flux of gamma-rays in the primary cosmic ray flux are determined in an energy range of ${10}^{14} - {10}^{18}$ eV. The analysis is performed by selecting air showers with a low muon content as expected for gamma-ray-induced showers compared to air showers induced by energetic nuclei. The best upper limit of the fraction of gamma-rays to the total cosmic ray flux is obtained at $3.7 \times {10}^{15}$ eV with $1.1 \times {10}^{-5}$. Translated to an absolute gamma-ray flux this sets constraints on some fundamental astrophysical models, such as the distance of sources for at least one of the IceCube neutrino excess models.Comment: Published in The Astrophysical Journal, Volume 848, Number 1. Posted on: October 5, 201