Antimicrobial resistance and One Health.

Antimicrobial resistance is one of the major health problems we face in the 21st century. Nowadays we cannot understand global health without the interdependence between the human, animal and environmental dimensions. It is therefore logical to adopt a "One Health" approach to address this problem. In this review we show why a collaboration of all sectors and all professions is necessary in order to achieve optimal health for people, animals, plants and our environment.

Harmonisation of in-silico next-generation sequencing based methods for diagnostics and surveillance.

Improvements in cost and speed of next generation sequencing (NGS) have provided a new pathway for delivering disease diagnosis, molecular typing, and detection of antimicrobial resistance (AMR). Numerous published methods and protocols exist, but a lack of harmonisation has hampered meaningful comparisons between results produced by different methods/protocols vital for global genomic diagnostics and surveillance. As an exemplar, this study evaluated the sensitivity and specificity of five well-established in-silico AMR detection software where the genotype results produced from running a panel of 436 Escherichia coli were compared to their AMR phenotypes, with the latter used as gold-standard. The pipelines exploited previously known genotype-phenotype associations. No significant differences in software performance were observed. As a consequence, efforts to harmonise AMR predictions from sequence data should focus on: (1) establishing universal minimum to assess performance thresholds (e.g. a control isolate panel, minimum sensitivity/specificity thresholds); (2) standardising AMR gene identifiers in reference databases and gene nomenclature; (3) producing consistent genotype/phenotype correlations. The study also revealed limitations of in-silico technology on detecting resistance to certain antimicrobials due to lack of specific fine-tuning options in bioinformatics tool or a lack of representation of resistance mechanisms in reference databases. Lastly, we noted user friendliness of tools was also an important consideration. Therefore, our recommendations are timely for widespread standardisation of bioinformatics for genomic diagnostics and surveillance globally.

"Candidatus Rickettsia andeanae" en Amblyomma tigrinum, San Luis, Argentina

El objetivo del estudio fue detectar especies del género Rickettsia en garrapatas de la especie Amblyomma tigrinum colectadas sobre carnívoros domésticos y en sangre de caninos domésticos de la provincia de San Luis (Argentina). Entre 2013 y 2015 se colectaron 56 garrapatas adultas de la especie A. tigrinum sobre caninos y felinos domésticos, y se obtuvieron 65 muestras sanguíneas de caninos. Tres garrapatas resultaron positivas mediante la amplificación de un fragmento del espacio intergénico 23S-5S ARNr del género Rickettsia, lográndose secuenciar uno de los productos positivos. La muestra positiva secuenciada también resultó positiva por PCRs de los fragmentos de los genes gltA y ompA. Las secuencias obtenidas resultaron tener una identidad del 100 % de identidad con "Candidatus Rickettsia andeanae". Todas las muestras sanguíneas resultaron negativas. "Ca. R. andeanae" no ha sido asociada con enfermedad en humanos o animales, sin embargo, es necesario realizar nuevas investigaciones para lograr un mayor conocimiento del riesgo potencial de transmisión de rickettsiosis en la región.

The aim of this study was to detect species of Rickettsia in Amblyomma tigrinum ticks collected from domestic carnivores and blood of domestic dogs of San Luis (Argentina). Between 2013 and 2015, 56 adults of A. tigrinum from dogs and cats and 65 blood from dogs were collected. Three ticks were positive by amplification of a 23S-5S rRNA fragment, and the sequence of one of the positive products was obtained. The positive sample sequenced was positive by PCRs of fragments of genes gltA and ompA. The sequences obtained were 100% identical with "Candidatus Rickettsia andeanae". All blood samples were negative. "Ca. R. andeanae" has not been associated with disease in humans or animals; however, further research is necessary to achieve greater awareness of the potential risk of transmission of rickettsial diseases in the region.

Bismuth labeling for the CT assessment of local administration of magnetic nanoparticles.

Many therapeutic applications of magnetic nanoparticles involve the local administration of nanometric iron oxide based materials as seeds for magnetothermia or drug carriers. A simple and widespread way of controlling the process using x-ray computed tomography (CT) scanners is desirable. The combination of iron and bismuth in one entity will increase the atenuation of x-rays, offering such a possibility. In order to check this possibility core-shell nanocrystals of iron oxide@bismuth oxide have been synthesized by an aqueous route and stabilized in water by polyethylene glycol (PEG), and we have evaluated their ability to generate contrast by CT and magnetic resonance imaging (MRI) to measure the radiopacity and proton relaxivities using phantoms. High-resolution scanning transmission electron microscopy (STEM) revealed that the material consists of a highly crystalline 8 nm core of maghemite and a 1 nm shell of bismuth atoms either isolated or clustered on the nanocrystal's surface. The comparison of µCT and MRI images of mice acquired in the presence of the contrast shows that when local accumulations of the magnetic nanoparticles take place, CT images are more superior in the localization of the magnetic nanoparticles than MRI images, which results in magnetic field inhomogeneity artifacts.

Structural determination of Bi-doped magnetite multifunctional nanoparticles for contrast imaging.

To determine with precision how Bi atoms are distributed in Bi-doped iron oxide nanoparticles their structural characterization has been carried out by X-ray absorption spectroscopy (XAS) recorded at the K edge of Fe and at the L3 edge of Bi. The inorganic nanoparticles are nominally hybrid structures integrating an iron oxide core and a bismuth oxide shell. Fe K-edge XAS indicates the formation of a structurally ordered, non-stoichiometric magnetite (Fe3-δO4) phase for all the nanoparticles. The XAS spectra show that, in the samples synthesized by precipitation in aqueous media and laser pyrolysis, the Bi atoms neither enter into the iron oxide spinel lattice nor form any other mixed Bi-Fe oxides. No modification of the local structure around the Fe atoms induced by the Bi atoms is observed at the Fe K edge. In addition, contrary to expectations, our results indicate that the Bi atoms do not form a well-defined Bi oxide structure. The XAS study at the Bi L3 edge indicates that the environment around Bi atoms is highly disordered and only a first oxygen coordination shell is observed. Indefinite [BiO6-x(OH)x] units (isolated or aggregated forming tiny amorphous clusters) bonded through hydroxyl bridges to the nanoparticle, rather than a well defined Bi2O3 shell, surround the nanoparticle. On the other hand, the XAS study indicates that, in the samples synthesized by thermal decomposition, the Bi atoms are embedded in a longer range ordered structure showing the first and second neighbors.

Facilitated ion transfer of protonated primary organic amines studied by square wave voltammetry and chronoamperometry.

The transfer of the protonated forms of heptylamine, octylamine, decylamine, procaine and procainamide facilitated by dibenzo-18-crown-6 from water to a solvent polymeric membrane has been investigated by using cyclic square wave voltammetry. The experimental voltammograms obtained are in good agreement with theoretical predictions. The values of the standard ion transfer potential, complexation constant and diffusion coefficient in water have been obtained from these experiments, and have been used to draw some conclusions about the lipophilicity of these species and the relative stability of the organic ammonium complexes with dibenzo-18-crown-6. The results have been compared with those provided by linear sweep voltammetry. Calibration graphs were obtained with both techniques. An interesting chronoamperometric method for the determination of the diffusion coefficient of the target ion in the membrane has been developed and applied to all these protonated amines.

Combined staged therapy of complex arteriovenous malformations: initial experience.

OBJECTIVES: Definitive treatment of complex supratentorial arteriovenous malformations (AVMs) has been classically assigned to ruptured or progressively symptomatic cases. The aim of this study is to report our initial experience in the treatment of complex AVMs by means of staged embolization with Onyx followed by microsurgery. MATERIAL AND METHODS: Thirteen consecutive patients with supratentorial Spetzler-Martin grades III, IV and V AVMs were treated between January 2009 and June 2010. Mean age at the beginning of the therapy was 34. All patients were symptomatic. Mean AVM size was 48 mm, and mean volume prior to embolization was 47 ml. RESULTS: Mean number of endovascular procedures was 3, and mean volumetric obliteration prior to surgery was 79.2%. Mean time between two embolizations was 24 days. One patient showed a non-disabling complication after endovascular procedures. Mean time between the last embolization and surgery was 42 days. Two patients showed disabling complications after surgery, and one patient showed a non-disabling complication. Follow-up angiography showed the complete removal of permeable AVM in all patients. According to the modified Rankin Scale, all patients were non-dependent concerning daily life activity at 6-month follow-up. One-year follow-up angiography has been performed in 11 patients so far showing an absence of permeable AVM in spite of the remainder intravascular Onyx. CONCLUSIONS: Staged preoperative embolization with Onyx followed by microsurgery has made possible 100% cure of complex AVMs with 0% mortality, 15.4% disabling complications and 15.4% non-disabling complications. Complete Onyx resection is not essential to achieve the cure of the patient.

Efecto de la aplicación en precosecha y en poscosecha de 1-mcp en la maduración de pitahaya amarilla (Selenicerus megalanthus Haw) / Effect of pre- and postharvest application of 1-methylcyclopropene on the maturation of yellow pitaya (Selenicerus megalanthus Haw)

The effect of pre- and postharvest applications of 200 and 400 μgL-1 aqueous solutions of 1-methylcyclopropene (1-MCP) on yellow pitaya (maturity stage 3) was assessed. Changes in respiratory rate, color, firmness, soluble solids content, titratable acidity, maturity index, weight loss and commercial preservation were measured. Results showed that the preharvest application of 400 μgL-1 1-MCP enhanced fruit color, preserved firmness, and reduced weight loss and maturity index of fruits. It is suggested that these results were explained by the reduction of available membrane receptors able to bind ethylene, thus increasing ethylene sensitivity and response magnitude. The preharvest application of 1-MCP could potentially be used to accelerate pitaya fruit ripening. The preharvest application of 200 μgL-1 1-MCP resulted in smaller changes in color and titratable acidity vs. control. Total soluble solids and pH were not significantly affected by the treatments. The postharvest application of 1-MCP maintained the texture of fruits by three additional days when compared to the untreated control.

Comparative exposure to antipsychotic medications in immigrant and native-born populations of a Spanish health region.

BACKGROUND: Raised rates of psychoses among ethnic minorities have been reported. Exposure to antipsychotic medications can give information on mental illness management and ethnic-related differences. OBJECTIVE: To compare exposure to antipsychotic medications in immigrant and native-born populations in Spain. METHOD: Descriptive cross-sectional study of the dispensation of antipsychotic medications to the population aged 15 to 64years, in a Spanish Health Region during 2008. RESULTS: 1.9% of the native-born population was exposed to antipsychotic medications as compared to 0.4% of the immigrant population. Native-born women were exposed from 1.8 to 5.3 times more and native-born men from 3.6 to 6.3 times more than immigrants of the same gender. The least exposed were persons from Eastern Europe and men from sub-Saharan Africa. Active ingredients prescribed were similar between the two groups. Of the immigrant group, 15.7% were admitted to a psychiatric ward as compared to 6.4% of the native-born population. In the former, non-specific diagnoses were predominant. CONCLUSIONS: All immigrant groups had lower exposure to antipsychotic medications, were admitted to inpatient care more often and had less specific diagnoses. Both diagnostic processes and adherence to treatment need improvement in the regional immigrant population.

Desempeño de las funciones esenciales de salud pública en tres municipios, Antioquia-Colombia, 2011 / Performance measurement of essential public health functions in three municipalities, Antioquia-Colombia, 2011

OBJETIVO: medir el desempeño de las Funciones Esenciales en Salud Pública (FESP) en tres municipios que corresponden a la zona Penderisco del suroeste antioqueño (Concordia, Betulia y Salgar) en 2011. METODOLOGIA: se realizó un estudio descriptivo transversal en los tres municipios. Se adaptó el instrumento de medición de las FESP en el ámbito nacional, elaborado por la OPS para aplicarlo localmente, se ajustó a las competencias y campos de acción de las autoridades municipales, se suprimieron preguntas no pertinentes para el nivel y se recalcularon las fórmulas que generaban el puntaje y los indicadores. El instrumento se aplicó a un grupo de expertos en cada municipio. RESULTADOS:en la zona Penderisco, se encontraron tres funciones FESP1, FESP2 y FESP4 con desempeño óptimo. Las FESP3, FESP5, FESP6, FESP7, FESP8, FESP9 y FESP11 con desempeño medio superior y la FESP10 un desempeño mínimo. Dos indicadores de desarrollo de capacidades e infraestructura para la salud pública, fueron clasificados como debilidades, coincidente en los tres municipios: conocimientos, habilidades y mecanismos para revisar, perfeccionar y hacer cumplir el marco regulatorio y el desarrollo de la capacidad institucional de investigación. CONCLUSIONES: a pesar de los esfuerzos realizados por los países para mejorar el desempeño de las FESP, el desarrollo es incipiente con algunas excepciones, este mismo esquema se refleja en los municipios estudiados. Pocas funciones están clasificadas en desempeño óptimo y como fortalezas. El desarrollo de capacidades e infraestructura para soportar el desarrollo de las FESP es débil.

OBJETIVE: to measure the performance of the Essential Public Health Functions (EPHF) in three municipalities from the Penderisco area of Southwestern Antioquia (a zone encompassing three municipalities: Betulia, Concordia, and Salgar) in 2011. METHODOLOGY: we conducted a cross-sectional descriptive study in three municipalities. To this end, we adapted the instrument for measuring EPHF for use in Colombia. The instrument was developed by the paho, and we implemented its adapted version locally. The instrument was adjusted to the skills and fields of action of the municipal authorities, the questions that were not relevant for the local context were removed, and the formulas for generating scores and indicators were re-calculated. The instrument was applied to a group of experts in each municipality. RESULTS: in the Penderisco zone, three functions had optimal performance: EPHF1, EPHF4, EPHF2. Additionally, the functions labeled EPHF3, EPHF5, EPHF6, EPHF7, EPHF8, EPHF9, and EPHF11 had above average performance. EPHF10, in turn, showed minimum performance. Two indicators of development of capacity and infrastructure for public health were classified as weaknesses, namely: knowledge, skills, and mechanisms to review, refine and enforce the regulatory framework and development of institutional research capacity. This is consistent in the three municipalities. CONCLUSIONS: In spite of the efforts made by countries to improve the performance of the essential public health functions, development is still budding; the same scenario is seen in the studied municipalities. Few functions had optimal performance and were considered strengths and capacity development and the infrastructure for supporting the development of essential public health functions are weak.

The profile of general practitioners (GPs) who publish in selected family practice journals.

BACKGROUND: Providing support for research is one of the key issues in the ongoing attempts to improve Primary Care. However, when patient care takes up a significant part of a GP's time, conducting research is difficult. In this study we examine the working conditions and profile of GPs who publish in three leading medical journals and propose possible remedial policy actions. FINDINGS: The authors of all articles published in 2006 and 2007 in three international Family Medicine journals - Annals of Family Medicine, Family Practice, and Journal of Family Practice - were contacted by E-mail. They were asked to complete a questionnaire investigating the following variables: availability of specific time for research, time devoted to research, number of patients attended, and university affiliation. Only GPs were included in the study. Three hundred and ten relevant articles published between 2006 and 2007 were identified and the authors contacted using a survey tool. 124 researchers responded to our questionnaire; 45% of respondents who were not GPs were excluded. On average GPs spent 2.52 days per week and 6.9 hours per day on patient care, seeing 45 patients per week. Seventy-five per cent of GPs had specific time assigned to research, on average 13 hours per week; 79% were affiliated to a university and 69% held teaching positions. CONCLUSIONS: Most GPs who publish original articles in leading journals have time specifically assigned to research as part of their normal working schedule. They see a relatively small number of patients. Improving the working conditions of family physicians who intend to investigate is likely to lead to better research results.

Dirección por objetivos y su impacto sobre la calidad de la prescripción de los especialistas al alta y en consultas externas / Management by objectives and its impact on specialist prescription quality at discharge and in external consultations

Objetivo Comprobar que la aplicación de una política de dirección por objetivos basada en la coordinación de Farmacia Hospitalaria, Atención Primaria y Dirección Médica, mejora los indicadores de calidad de la prescripción en el ámbito de la asistencia especializada y reduce la prescripción inducida no deseada en el ámbito de la asistencia primaria. Metodología Estudio de intervención cuasi-experimental controlado sobre la prescripción médica al alta y en las consultas externas de hospital durante 4 años. En el hospital A se aplicó el ciclo de calidad: evaluación, detección de oportunidades de mejora, puesta en marcha de medidas correctoras y reevaluación, y en el hospital B que se uso como control no se aplicó. Los indicadores escogidos fueron: % de prescripciones de especialidades genéricas, % de prescripciones de novedades terapéuticas sin valor añadido y % de prescripciones de IECA recomendados. Resultados En el hospital A, entre el último año de intervención y el año preintervención, se produjo un aumento en los indicadores 1 y 3 siendo estadísticamente significativo en ambos. En el hospital A se consiguió disminuir el indicador 2 hasta un 4,5%, mientras que en B aumentó hasta 8,8%, siendo estadísticamente significativa la diferencia entre los dos hospitales. Conclusión la propuesta de objetivos de mejora de la prescripción ligados a estímulos de tipo económico es una acción efectiva para aumentar el valor de algunos indicadores de calidad de la prescripción (AU)

Objective To verify that implementing a policy of management by objectives, based on collaboration between hospital pharmacy, primary care and specialised medical managers, improves prescription quality indicators in specialised care and reduces unwanted “induced” prescriptions (i.e. those issued by specialists, hospital doctors or the patients themselves) in primary care. Method A four year quasi-experimental controlled intervention study on prescription at discharge and in outpatient hospital consultations was conducted. In hospital A, a quality cycle was applied: assessment, identifying improvement opportunities, implementing corrective actions and re-assessment. However, it was not applied in control hospital B. The indicators chosen were the percentage of generic medicines prescribed, the percentage of prescriptions for new therapies with no added value and the percentage of prescriptions for ACE inhibitors recommended. Results In hospital A, an increase in indicators 1 and 3 has been observed, both being statistically significant, between the last year of intervention and the year previous to intervention. Hospital A managed to reduce indicator 2 to 4.5%, while this indicator increased in hospital B to 8.8%. Furthermore, a statistically significant difference in indicators between the two hospitals has been registered. Conclusion Pay-for-Performance programs in prescription practices of hospital physicians are effective actions to improve quality indicators of medication use (AU)

Ion transfer through solvent polymeric membranes driven by an exponential current flux.

General analytical equations which govern ion transfer through liquid membranes with one and two polarized interfaces driven by an exponential current flux are derived. Expressions for the transient and stationary E-t, dt/dE-E and dI/dE-E curves are obtained, and the evolution from transient to steady behaviour has been analyzed in depth. We have also shown mathematically that the voltammetric and stationary chronopotentiometric I(N)-E curves are identical (with E being the applied potential for voltammetric techniques and the measured potential for chronopotentiometric techniques), and hence, their derivatives provide identical information.

Management by objectives and its impact on specialist prescription quality at discharge and in external consultations.

OBJECTIVE: To verify that implementing a policy of management by objectives, based on collaboration between hospital pharmacy, primary care and specialised medical managers, improves prescription quality indicators in specialised care and reduces unwanted "induced" prescriptions (i.e. those issued by specialists, hospital doctors or the patients themselves) in primary care. METHOD: A four year quasi-experimental controlled intervention study on prescription at discharge and in outpatient hospital consultations was conducted. In hospital A, a quality cycle was applied: assessment, identifying improvement opportunities, implementing corrective actions and re-assessment. However, it was not applied in control hospital B. The indicators chosen were the percentage of generic medicines prescribed, the percentage of prescriptions for new therapies with no added value and the percentage of prescriptions for ACE inhibitors recommended. RESULTS: In hospital A, an increase in indicators 1 and 3 has been observed, both being statistically significant, between the last year of intervention and the year previous to intervention. Hospital A managed to reduce indicator 2 to 4.5%, while this indicator increased in hospital B to 8.8%. Furthermore, a statistically significant difference in indicators between the two hospitals has been registered. CONCLUSION: Pay-for-Performance programs in prescription practices of hospital physicians are effective actions to improve quality indicators of medication use.

Covered metal stents for the treatment of biliary complications after orthotopic liver transplantation.

BACKGROUND: Biliary complications, a major source of morbidity after orthotopic liver transplantation (OLT), are increasingly being treated by endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic management has been shown to be superior to percutaneous therapy and surgery. Covered self-expandable metal stents (CSEMSs) may be an alternative to the current endoscopic standard treatment with periodic plastic stent replacement. OBJECTIVE: To assess the safety and efficacy of temporary CSEMS insertion for biliary complications after OLT. METHODS: From November 2001 to December 2009, the 242 OLT performed in 226 patients included 67 cases that developed post-OLT leaks or strictures (29.6%), excluding ischemic biliary complications. CSEMSs were used in 22 patients (33%), 18 male and 4 female, with an overall median age of 55 years (range, 29-69). In-house OLT patients underwent an index ERCP at 26 days (range, 8-784) after OLT. Their records were reviewed to determine ERCP findings, technical success, and clinical outcomes. RESULTS: ERCP with sphincterotomy was performed in all 22 patients, revealing 18 with biliary strictures alone (82%), 3 with strictures and leaks (14%), and 1 with strictures and choledocholithiasis (4%). All strictures were anastomotic. All patients had 1-2 plastic stents inserted across the anastomosis (11 had prior balloon dilation); stones were successfully removed, for an initial technical success rate of 100% (22/22). CSEMSs, were placed at the second ERCP in 14 patients, at the third in 7, and at the fourth in 1. With a median follow-up of 12.5 months (range, 3-25) after CSEMS removal, 21/22 patients (95.5%) remain stricture free and one relapsed, requiring repeat CSEMS insertion. Four patients experienced pain after CSEMS insertion. At CSEMS removal, migration was noted in 5 cases, into either the distal duodenum (n=4) or the proximal biliary tree (n=1), and embedding was seen in 1 case. There were no serious complications; no patients needed hepatojejunostomy. CONCLUSIONS: ERCP is a safe first-line approach for post-OLT biliary complications. It was highly successful in a population with anastomotic leaks and strictures. The therapeutic role of ERCP to manage biliary complications after OLT in the long term is not well known. In our experience, the high rate (close to 95%) of efficacy and its relative safety allowed us to use CSEMS to manage refractory biliary post-OLT strictures. CSEMS insertion may preclude most post-OLT hepatojejunostomies.

Liofilización de pitahaya amarilla (Selenicereus megalanthus) / Freeze-drying in yellow pitahaya (Selenicereus megalanthus)

La liofilización es una alternativa de interés como método de conservación de alimentos, la cual permite prolongar el tiempo de vida útil manteniendo significativamente las propiedades físicas y fisicoquímicas relacionadas con su calidad. El objetivo de este trabajo fue evaluar el efecto de la liofilización y la osmoliofilización sobre las cinéticas de congelación y de secado, la actividad de agua, el volumen, la porosidad y la capacidad de rehidratación en rodajas de pitahaya amarilla (Selenicereus megalanthus). Como pretratamiento osmótico a la liofilización (osmoliofilización), las rodajas se sumergieron en una solución de sacarosa con 55 ºBrix a 25ºC; se congelaron a -35°C, la sublimación se llevó a presión de vacío de 8 Pa y el secado se realizó desde -35 hasta 35°C. Los resultados de los tratamientos evidenciaron, al final del proceso, diferencias significativas en la porosidad, volumen y capacidad de rehidratación (que fueron mayores para el tratamiento liofilizado), mientras que la cinética de secado y la actividad de agua no presentaron diferencias significativas. El tratamiento de liofilización fue adecuado para la conservación de rodajas de pitahaya amarilla, ya que permitió reducir la actividad de agua por debajo de 0,4; conservó significativamente el volumen y presentó alta capacidad de rehidratación.

Freeze-drying is an interesting alternative as a food preservation method allowing to extend the shelf life and significantly preserving physical and physicochemical properties related to quality. The objective of this study was to evaluate the effect of freeze-drying and osmo-freeze-drying on the kinetics of freezing and drying, water activity, volume, porosity and rehydration capacity of sliced yellow pitahaya (Selenicereus megalanthus). As osmotic pretreatment to freeze-drying (osmo-freeze-drying), slices were immersed in a sucrose solution at 55°Brix. The slices were frozen at -35°C. The sublimation was carried at vacuum pressure of 8 Pa and drying was carried out from -35 to 35°C. The results of these treatments at the end of the process showed significant differences in porosity, volume and rehydration capacity (being higher for freeze-drying treatment), while the kinetics of drying and water activity were not significant. The freeze drying treatment was suitable for the preservation of sliced yellow pitahaya, because it helped to decrease water activity below 0.4, preserved and showed significant volumes of high rehydration capacity.