Calidad de vida en pacientes con tumor vesical no músculo-invasivo sometidos a tratamiento adyuvante intravesical / Quality of life in patients with non-muscle invasive bladder tumor undergoing adjuvant intravesical treatment

Introducción El objetivo del estudio fue establecer posible relación entre los tratamientos con mitomicina-C (MMC) y bacilo de Calmette-Guérin (BCG) y la afectación en la calidad de vida. Material y métodos Estudio cuasiexperimental, prospectivo y longitudinal, recogiendo pacientes sometidos a tratamiento adyuvante en TVNMI. Se utilizaron los cuestionarios Short form-12 (SF-12) y Urogenital Distress Inventory-6 (UDI-6) para medir la calidad de vida. Se compararon las puntuaciones de los cuestionarios entre casos con MMC y BCG antes de iniciar la inducción (M1), a las 4 semanas (M2) y a los dos meses (M3). Resultados Se recogieron 90 pacientes, 54 en el grupo de BCG y 36 en el de MMC. Se comprobó que los pacientes con BCG percibían peor calidad de vida física comparados con los de MMC en M2 (OR:2,59, p=0,046). Además, se hallaron cambios significativos en la calidad de vida urinaria de los pacientes en tratamiento con MMC entre los diferentes momentos temporales (puntuación del UDI-6: 33,33 en M1, 27,78 en M2 y 16,67 en M3, p=0,001). Conclusiones No existen diferencias en la calidad de vida urinaria entre los pacientes tratados con MMC y BCG. Los pacientes con MMC muestran una recuperación significativa de la calidad de vida urinaria a partir de la finalización de la inducción, que aumenta aún más a los dos meses de la misma. Además, los pacientes tratados con BCG presentan peor calidad de vida física a las 4 semanas de tratamiento que aquellos tratados con MMC (AU)

Introduction The objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. Material and methods Quasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). Results Of the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). Conclusions There are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC (AU)

Quality of life in patients with non-muscle invasive bladder tumor undergoing adjuvant intravesical treatment.

INTRODUCTION: The objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. MATERIAL AND METHODS: Quasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). RESULTS: Of the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). CONCLUSIONS: There are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.

Competency assessment of residents of Intensive Care Medicine through a simulation-based objective structured clinical evaluation (OSCE). A multicenter observational study.

OBJECTIVES: The current official model of training in Intensive Care Medicine (ICM) in Spain is based on exposure to experiences through clinical rotations. The main objective was to determine the level of competency (I novice to V independent practitioner) achieved by the residents at the end of the 3rd year of training (R3) in ICM through a simulation-based OSCE. Secondary objectives were: (1) To identify gaps in performance, and (2) To investigate the reliability and feasibility of conducting simulation-based assessment at multiple sites. DESIGN: Observational multicenter study. SETTING: Thirteen Spanish ICU Departments. PARTICIPANTS: Thirty six R3. INTERVENTION: The participants performed on five, 15-min, high-fidelity crisis scenarios in four simulation centers. The performances were video recorded for later scoring by trained raters. MAIN VARIABLES OF INTEREST: Via a Delphi technique, an independent panel of expert intensivists identified critical essential performance elements (CEPE) for each scenario to define the levels of competency. RESULTS: A total of 176 performances were analyzed. The internal consistency of the check-lists were adequate (KR-20 range 0.64-0.79). Inter-rater reliability was strong [median Intraclass Correlation Coefficient across scenarios: 0.89 (0.65-0.97)]. Competency levels achieved by R3 were: Level I (18.8%), II (35.2%), III (42.6%), IV/V (3.4%). Overall, a great heterogeneity in performance was observed. CONCLUSION: The expected level of competency after one year in the ICU was achieved only in half of the performances. A more evidence-based educational approach is needed. Multiple center simulation-based assessment showed feasibility and reliability as an evaluation method of competency. TRIAL REGISTRATION: COBALIDATION. NCT04278976. (https://register. CLINICALTRIALS: gov).

Análisis de la aceptación y validez de los métodos utilizados para la implementación de un programa de formación basado en competencias en un servicio de Medicina Intensiva de un hospital universitario de referencia / Acceptance and validity of the methods used to implement a competency based medical education programme in an Intensive Care Department of a teaching referral center

Objetivos: 1) Determinar la satisfacción de tutores y residentes con la metodología utilizada para la implementación de CoBaTrICE, y 2) determinar la validez y la fiabilidad de las escalas de valoración global diseñados ad hoc para analizar el desempeño de los residentes con fines formativos. Diseño: Estudio prospectivo de cohortes. Participantes: Todos los residentes y tutores del Servicio de Medicina Intensiva del Hospital Universitario y Politécnico La Fe de Valencia. Intervención: En marzo del 2016 se inició la implementación de CoBaTrICE sustentada en: 1) formación de los tutores en técnicas de retroalimentación; 2) realización por los residentes de múltiples ejercicios reales de evaluación objetiva y estructurada para adquirir las competencias del programa, y 3) uso de un portafolio electrónico para registrar las evidencias del progreso y estimular la reflexión. Métodos: La satisfacción con CoBaTrICE se evaluó mediante una encuesta realizada tras 9 meses de implementación a los 15 residentes y 5 tutores del servicio. Se preguntó sobre la metodología de las evaluaciones, calidad de la retroalimentación, autorregulación del aprendizaje y utilidad del portafolio. Se determinaron la consistencia interna (alfa de Cronbach), índices de generalizabilidad y fiabilidad interjueces (índice de correlación intraclase) de las escalas de valoración global. Resultados: La aplicación de CoBaTrICE fue satisfactoria en todas las dimensiones estudiadas. Se constataron la validez y la fiabilidad de las escalas de valoración utilizadas. Conclusiones: La metodología utilizada para implementar CoBaTrICE fue valorada positivamente por tutores y residentes. Las escalas de valoración global utilizadas en la evaluación formativa demostraron ser válidas, fiables y reproducibles. (AU)

Objectives; 1. To determine the satisfaction of tutors and residents with a specific methodology used to implement CoBaTrICE; 2. To determine the reliability and validity of the global rating scales designed ad hoc to assess the performance of the residents for training purposes. Design Prospective cohort study Participants All the residents and tutors of the ICU Department of the Hospital Universitario y Politécnico la Fe de Valencia. Intervention CoBaTrICE implementation started in March 2016, it was based on: 1) Training the tutors in feedback techniques; 2) Performing multiple objective and structured work based assessments to achieve the competences of the program; and 3) The use of an electronic portfolio to promote learning reflection and to collect the evidence that learning was taking place. Methods The acceptance of CoBaTrICE was explored through a satisfaction survey conducted after 9 months of implementation of the training program. The 15 residents and 5 tutors of the ICU Department were asked about the methodology of the formative assessments, the quality of the feedback, self-learning regulation and the electronic portfolio usefulness. The validity of the global rating scales was assessed through the tests alfa de Cronbach, reliability and generalizability indexes, and intraclass correlation coefficient. Results The implementation of CoBaTrICE was satisfactory in all the dimensions studied. The global rating scales used for formative purposes showed reliability and validity. Conclusions The methodology used to implement CoBaTrICE was highly valued by tutors and residents. The global rating scales used for formative purposes showed reliability and validity. (AU)

Acceptance and validity of the methods used to implement a competency based medical education programme in an Intensive Care Department of a teaching referral center.

OBJECTIVES: 1. To determine the satisfaction of tutors and residents with a specific methodology used to implement CoBaTrICE. 2. To determine the reliability and validity of the global rating scales designed ad hoc to assess the performance of the residents for training purposes. DESIGN: Prospective cohort study. PARTICIPANTS: All the residents and tutors of the ICU Department of the Hospital Universitario y Politécnico la Fe de Valencia. INTERVENTION: CoBaTrICE implementation started in March 2016, it was based on: (1) Training the tutors in feedback techniques; (2) Performing multiple objective and structured work based assessments to achieve the competences of the program; and (3) The use of an electronic portfolio to promote learning reflection and to collect the evidence that learning was taking place. METHODS: The acceptance of CoBaTrICE was explored through a satisfaction survey conducted after 9 months of implementation of the training program. The 15 residents and 5 tutors of the ICU Department were asked about the methodology of the formative assessments, the quality of the feedback, self-learning regulation and the electronic portfolio usefulness. The validity of the global rating scales was assessed through the tests alfa de Cronbach, reliability and generalizability indexes, and intraclass correlation coefficient. RESULTS: The implementation of CoBaTrICE was satisfactory in all the dimensions studied. The global rating scales used for formative purposes showed reliability and validity. CONCLUSIONS: The methodology used to implement CoBaTrICE was highly valued by tutors and residents. The global rating scales used for formative purposes showed reliability and validity.

In reply to the letter to the editor regarding "Palisade cartilage tympanoplasty compared to one-piece composite cartilage-perichondrium grafts for transcanal endoscopic treatment of subtotal tympanic membrane perforations: a retrospective study".

This is a reply letter to the manuscript "The size and diameter of pieces of cartilage are not fixed for the palisade technique and one-piece technique", regarding the elevation of a tympanomeatal flap and keratin pearl formation in "Palisade cartilage tympanoplasty compared to one-piece composite cartilage-perichondrium grafts for transcanal endoscopic treatment of subtotal tympanic membrane perforations: a retrospective study" ( https://doi.org/10.1007/s00405-020-05947-3 ).

Revisión sistemática del tratamiento de la espasticidad en el adulto con daño cerebral adquirido / Systematic review of the treatment of spasticity in acquired adult brain damage

La espasticidad es un trastorno motor, caracterizado por un aumento del tono muscular, y que aparece como consecuencia de un trastorno del sistema nervioso central, dando lugar a déficit y discapacidad, con deterioro de la calidad de vida. En el daño cerebral adquirido del adulto, la espasticidad constituye un problema grave y frecuente, apareciendo en un 20-30% de pacientes con ictus y en un 13-20% de pacientes con traumatismo craneoencefálico moderado-grave. El objetivo principal de este trabajo es realizar una revisión sistemática de los tratamientos utilizados en la espasticidad del paciente adulto con daño cerebral adquirido secundario a ictus y traumatismo craneoencefálico. Como objetivo secundario se pretende averiguar las principales escalas de valoración utilizadas para la medida de la espasticidad en estos pacientes. Se ha realizado una búsqueda sistemática de ensayos controlados aleatorizados, publicados entre el 1 de enero de 2013 y 30 de junio de 2017 en inglés y castellano, en las bases de datos PubMed, Biblioteca Cochrane plus y Ovid. Se han seleccionado finalmente 17 estudios, con una calidad metodológica al menos aceptable, según la escala de Jadad. Los tratamientos más frecuentemente investigados son la toxina botulínica, especialmente el serotipo A, junto a medidas rehabilitadoras. Las escalas clínicas son las más frecuentemente utilizadas para la evaluación de la espasticidad

Spasticity is a motor disorder characterised by an increase in muscle tone that appears as a consequence of a central nervous system disorder, leading to deficit and disability and impairing quality of life. In acquired adult brain damage, spasticity is a severe and frequent problem, appearing in 20-30% of patients with stroke and in 13-20% of patients with moderate-severe traumatic brain injury. The main objective of this study was to perform a systematic review of the treatments used in spasticity in adult patients with acquired brain damage secondary to stroke and head trauma. A systematic search of randomised controlled trials, published between January 1, 2013 and June 30, 2017 in English and Spanish, was carried out in the PubMed, Cochrane plus Library and Ovid databases. We finally selected 17 studies, with methodological quality that was at least acceptable according to the Jadad scale. The most frequently investigated treatments are botulinum toxin, especially serotype A, together with rehabilitative measures. Clinical scales are the most frequently used to assess spasticity

[Systematic review of the treatment of spasticity in acquired adult brain damage]. / Revisión sistemática del tratamiento de la espasticidad en el adulto con daño cerebral adquirido.

Spasticity is a motor disorder characterised by an increase in muscle tone that appears as a consequence of a central nervous system disorder, leading to deficit and disability and impairing quality of life. In acquired adult brain damage, spasticity is a severe and frequent problem, appearing in 20-30% of patients with stroke and in 13-20% of patients with moderate-severe traumatic brain injury. The main objective of this study was to perform a systematic review of the treatments used in spasticity in adult patients with acquired brain damage secondary to stroke and head trauma. A systematic search of randomised controlled trials, published between January 1, 2013 and June 30, 2017 in English and Spanish, was carried out in the PubMed, Cochrane plus Library and Ovid databases. We finally selected 17 studies, with methodological quality that was at least acceptable according to the Jadad scale. The most frequently investigated treatments are botulinum toxin, especially serotype A, together with rehabilitative measures. Clinical scales are the most frequently used to assess spasticity.

Factors related to early castration resistance in metastatic prostate cancer. Results from the National Prostate Cancer Registry in Spain. / Factores relacionados con la resistencia a la castración precoz en el cáncer de próstata metastásico. Resultados del Registro nacional de cáncer de próstata en España.

INTRODUCTION: The objective of the study was to determine the factors independently related with the development of castration resistance (CR) in prostate cancer (PC) in the medium term. MATERIAL AND METHODS: 155 patients diagnosed with metastatic PC with a follow-up of up to 39 months. Data taken from the National PC Registry. The evaluated variables were age, PSA, nadir PSA, Gleason, perineural invasion, TNM stages, and ADT type (intermittent/continuous). RESULTS: Mean follow-up 26,2±13,4 months. 47.1% developed early CR, with mean time until onset of 12,2±8,7 months. Univariate analysis the mean PSA was correlated with CR (290±905,1 ng/mL in non CR, 519,1±1437,2 ng/mL in CR, P<.001), mean age (73,3±8,3 years in non CR, 69,1±9,3 in CR P=.01), mean PSA nadir (15,5±57,3ng/mL in non CR, 15,9±23,7 ng/mL in CR, p<0,001), Gleason (in ≥8, HR:2,11. 95% CI: 1.22-3.65, p=0.006), and T stage (in T3-T4, HR: 2.85. 95% CI: 1.57-5.19, P<.001). Multivariate analysis the independent variables associated to CR are age (HR: 0.96. 95% CI: 0.94-0.99, P=.01), PSA nadir (HR: 1.65. 95% CI: 1,43-1,91, P<.001), and T3-T4 stage (HR: 2.11. 95% CI: 1.10-4.04, P=.02). CONCLUSIONS: PSA nadir and T3-T4 tumor stage at diagnosis are associated to an increased risk of developing CR. In addition, age at diagnosis is shown as a variable that decreases risk. Therefore, an older age would be associated with lower risk probability of CR in the medium term.

Cross-cultural adaptation and validation of the Spanish version of the Paediatric Throat Disorders Outcome Test (T-14).

OBJECTIVES: The Paediatric Throat Disorders Outcome Test (T-14) is a disease-specific questionnaire that parents are requested to complete; it aimed to assess the quality of life related to tonsil and adenoid disease or its treatment in children with throat disorders. The aim of this study was to validate the Spanish adaptation of the T-14, thus allowing comparison across studies and facilitating international multicentre projects. DESIGN, SETTING AND PARTICIPANTS: This was a multicentre prospective instrument validation study. Guidelines for the cross-cultural adaptation process from the original English-language scale into a Spanish-language version were followed. The psychometric properties (reproducibility, reliability, validity, responsiveness) of the Spanish version ("T-14-s" for "T-14-Spanish") were assessed in 50 consecutive children undergoing adeno/tonsillectomy (both before and 6 months after surgery) and in a separate cohort of 50 unaffected children in a comparable age range. MAIN OUTCOME MEASURES AND RESULTS: Test-retest reliability (γ = 0.83) and internal consistency reliability (α = 0.94) were adequate. The T-14-s demonstrated satisfactory construct validity (r > 0.40). The instrument showed excellent between-group discrimination (P < .0001) and a high responsiveness to change (effect size = 2.09). CONCLUSIONS: The Spanish version of the T-14 (T-14-s) is a valid tool for measuring the subjective severity of throat disorders, and its use is recommended.

Evolution of the clinical profile of patients with acute heart failure treated in Spanish emergency departments. / Evolución del perfil clínico de los pacientes con insuficiencia cardiaca aguda atendidos en servicios de urgencias españoles.

OBJECTIVE: To analyse the changes in epidemiology, outpatient and emergency department clinical care, and outcomes of patients treated for acute heart failure (AHF) in Spanish hospital emergency departments (HEDs) between 2007 and 2014. METHOD: A multicentre cohort study was conducted that consecutively included patients with AHF diagnosed in 9HEDs during 4 periods (2007, 2009, 2011 and 2014). The study analysed the changes observed in 20 variables corresponding to baseline data, outpatient care and emergency care data and outcome data. RESULTS: A total of 4,845 patients were included. There were significant changes in 13 variables: there was an increase in patients older than 80years (2007/2014: 45.9%/55.4%; P<.001) and a decrease in severe functional dependence (28.2%/19.7%; P<.001). In terms of long-term outpatient care, there was an increased use of beta-blockers (44.6%/57.8%; P=.002) and aldosterone antagonists (26.6%/37.7%; P<.05) among patients with reduced ejection fraction and an increase use of echocardiography (42.8%/56.2%; P=.001). The use of digoxin decreased (25.4%/16.9%; P=.005). In terms of emergency care, there was an increase in requests for troponins (54.6%/61.9%; P<.001), natriuretic peptides (7.8%/48.5%; P<.001) and the use of noninvasive ventilation (3.2%/6.9%; P=.004). Requests for endovenous perfusion drugs decreased (diuretics: 21.3%/10.4%; P<.001; nitrates: 21.3%/17.5%; P=.001; vasopressors: 4.2%/1.5%; P<.001). Finally, discharges directly from the emergency department without hospitalization increased (20.0%/25.9%; P<.001), and emergency department readmissions at 30days decreased (27.3%/17.6%; P=.007). Hospital mortality and mortality at 30days did not change. CONCLUSIONS: Changes in outcomes were detected during a 7-year period in patients with AHF treated in HEDs, with care that was more in line with the clinical guidelines. There are, however, areas for improvement. There was a noteworthy increase in outpatient follow-up without hospitalisation and a reduction in HED readmissions.

Simulación de alta fidelidad en España: de la ensoñación a la realidad / High fidelity simulation in Spain: from dreams to reality

La simulación clínica ha surgido como una potente herramienta para el aprendizaje y evaluación de las diferentes capacidades y actitudes en el ámbito de las Ciencias de la Salud, mediante el uso de tecnologías innovadoras, como los simuladores de alta fidelidad (HFS). Objetivo. Describir el estado actual de la dotación de equipos de simulación clínica de alta fidelidad en nuestro país e identificar sus características principales. Método. Estudio observacional descriptivo que analiza la información sobre los centros que poseen HSF en nuestro país. Resultados. Existen actualmente un total de 80 centros dotados de HFS en nuestro país, distribuidos principalmente en centros universitarios (43), centros hospitalarios y de urgencias (27), e institutos o centros de simulación (5), estando el resto (5) asociado a entidades de diversa titularidad. El desarrollo temporal de los HFS ha sido lentamente progresivo, experimentando un importante crecimiento en el último sexenio. En su mayoría (74%) cuentan con instalaciones específicas, equipos auxiliares (60%) y profesionales con dedicación compartida (80%). Está integrada ya en los programas de formación del 56% de los centros universitarios dotados de HFS. Conclusiones. Disponemos actualmente de un notable desarrollo de HFS en nuestro país, principalmente relacionados con la docencia médica pregrado universitaria y posgrado hospitalaria. Sería de utilidad diseñar una red de centros de formación en simulación de Ciencias de la Salud en España, que sea operativa, sostenible y reconocida, que permita optimizar la utilización de estos centros (AU)

Clinical simulation has emerged as a powerful new tool for the learning and assessment of different skills and attitudes in patient care, by using innovative technology such as high fidelity simulators (HFS). Objective. To describe the current state of high fidelity clinical simulation in Spain and its principal characteristics. Methods. Descriptive observational study that analyzes information on the clinical centers that have HFS in our country. Results. There are currently a total of 80 centers with HFS in our country, mainly distributed in university centers (43), hospital and emergency centers (27), simulation centers and institutes of simulation (5), and the rest (5) associated to entities of diverse ownership. The temporal development of HFS has been slowly progressive, with a significant growth in the last 6 years. The majority (74%) have specific facilities, auxiliary equipment (60%), and professionals with a shared commitment (80%). It is already integrated into the training programs in 56% of university centers with HFS. Conclusions. The development of HFS has been remarkable in our country, and is mainly related to university undergraduate and postgraduate clinical medical education. It would be useful to design a network of simulation training centers of Health Sciences in Spain, which would be operational, sustainable and recognized, to optimize the use of these facilities (AU)

[High fidelity simulation in Spain: from dreams to reality]. / Simulación de alta fidelidad en España: de la ensoñación a la realidad.

UNLABELLED: Clinical simulation has emerged as a powerful new tool for the learning and assessment of different skills and attitudes in patient care, by using innovative technology such as high fidelity simulators (HFS). OBJECTIVE: To describe the current state of high fidelity clinical simulation in Spain and its principal characteristics. METHODS: Descriptive observational study that analyzes information on the clinical centers that have HFS in our country. RESULTS: There are currently a total of 80 centers with HFS in our country, mainly distributed in university centers (43), hospital and emergency centers (27), simulation centers and institutes of simulation (5), and the rest (5) associated to entities of diverse ownership. The temporal development of HFS has been slowly progressive, with a significant growth in the last 6 years. The majority (74%) have specific facilities, auxiliary equipment (60%), and professionals with a shared commitment (80%). It is already integrated into the training programs in 56% of university centers with HFS. CONCLUSIONS: The development of HFS has been remarkable in our country, and is mainly related to university undergraduate and postgraduate clinical medical education. It would be useful to design a network of simulation training centers of Health Sciences in Spain, which would be operational, sustainable and recognized, to optimize the use of these facilities.

Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase.

The specific self-association of proteins into oligomeric complexes is a common phenomenon in biological systems to optimize and regulate their function. However, de novo structure determination of these important complexes is often very challenging for atomic-resolution techniques. Furthermore, in the case of homo-oligomeric complexes, or complexes with very similar building blocks, the respective positions of subunits and their assembly pathways are difficult to determine using many structural biology techniques. Here, an elegant and powerful approach based on small-angle neutron scattering is applied, in combination with deuterium labelling and contrast variation, to elucidate the oligomeric organization of the quaternary structure and the assembly pathways of 468 kDa, hetero-oligomeric and symmetric Pyrococcus horikoshii TET2-TET3 aminopeptidase complexes. The results reveal that the topology of the PhTET2 and PhTET3 dimeric building blocks within the complexes is not casual but rather suggests that their quaternary arrangement optimizes the catalytic efficiency towards peptide substrates. This approach bears important potential for the determination of quaternary structures and assembly pathways of large oligomeric and symmetric complexes in biological systems.

The TET2 and TET3 aminopeptidases from Pyrococcus horikoshii form a hetero-subunit peptidasome with enhanced peptide destruction properties.

TET aminopeptidases assemble as large homo-dodecameric complexes. The reason why prokaryotic genomes often encode a diverse set of TET peptidases homologues remains unclear. In the archaeon Pyrococcus horikoshii, PhTET1, PhTET2 and PhTET3 homo-oligomeric particles have been proposed to work in concert to breakdown intracellular polypeptides. When coexpressed in Escherichia coli, the PhTET2 and PhTET3 proteins were found to assemble efficiently as heteromeric complexes. Biophysical analysis demonstrated that these particles possess the same quaternary structure as the homomeric TET dodecamers. The same hetero-oligomeric complexes were immunodetected in P. horikoshii cell extracts analysed by sucrose gradient fractionation and ion exchange chromatography. The biochemical activity of a purified hetero-oligomeric TET particle, assessed on chromogenic substrates and on a complex mixture of peptides, reveals that it displays higher efficiency than an equivalent combination of homo-oligomeric TET particles. Interestingly, phylogenetic analysis shows that PhTET2 and PhTET3 are paralogous proteins that arose from gene duplication in the ancestor of Thermococcales. Together, these results establish that the PhTET2 and PhTET3 proteins are two subunits of the same enzymatic complex aimed at the destruction of polypeptidic chains of very different composition. This is the first report for such a mechanism intended to improve multi-enzymatic complex efficiency among exopeptidases.

Pyrococcus horikoshii TET2 peptidase assembling process and associated functional regulation.

Tetrahedral (TET) aminopeptidases are large polypeptide destruction machines present in prokaryotes and eukaryotes. Here, the rules governing their assembly into hollow 12-subunit tetrahedrons are addressed by using TET2 from Pyrococcus horikoshii (PhTET2) as a model. Point mutations allowed the capture of a stable, catalytically active precursor. Small angle x-ray scattering revealed that it is a dimer whose architecture in solution is identical to that determined by x-ray crystallography within the fully assembled TET particle. Small angle x-ray scattering also showed that the reconstituted PhTET2 dodecameric particle displayed the same quaternary structure and thermal stability as the wild-type complex. The PhTET2 assembly intermediates were characterized by analytical ultracentrifugation, native gel electrophoresis, and electron microscopy. They revealed that PhTET2 assembling is a highly ordered process in which hexamers represent the main intermediate. Peptide degradation assays demonstrated that oligomerization triggers the activity of the TET enzyme toward large polypeptidic substrates. Fractionation experiments in Pyrococcus and Halobacterium cells revealed that, in vivo, the dimeric precursor co-exists together with assembled TET complexes. Taken together, our observations explain the biological significance of TET oligomerization and suggest the existence of a functional regulation of the dimer-dodecamer equilibrium in vivo.

Aphysiologic performance on dynamic posturography in work-related patients.

It has been suggested that malingering should be suspected in patients suffering from dizziness or imbalance and who had a potential gain associated with insurance and worker's compensation claims. This study aimed to assess and compare the prevalence of aphysiologic performance on computerized dynamic posturography (CDP) in patients with the potential for secondary gain using a retrospective review of two groups of patients: work-related patients referred for dizziness and/or imbalance (Group 1) were compared against a group of patients with complaints of dizziness or imbalance, who had no history of work-related injury, or litigation procedures (Group 2). CDP and videonystagmography (VNG) were carried out in all patients. The Sensory Organization Test summaries were scored as normal, aphysiologic, or vestibular using the scoring method published by Cevette et al. in Otolaryngol Head Neck Surg 112:676-688 (1995). 24 out of 88 (27%) patients had aphysiologic CDP in Group 1 and 9 out of 51 (18%) in Group 2 but these differences were not significant (p > 0.05). Definite signs of vestibular dysfunction were found in 12 out of 24 (50%) of patients with aphysiologic performance in Group 1 although the presence of VNG abnormalities was significantly higher (p = 0.005) in Group 2. The hypothesis that the occupational group could show a significantly higher rate of aphysiologic results than a control group is not confirmed. Furthermore, VNG abnormalities were found in 50% of the work-related cases with non organic sway patterns. These results suggest that patient's complaints should be considered genuine in work-related cases and due caution exercised when evaluating aphysiologic CDP patterns.

Resultados de pruebas de control postural y función vestibular en 51 pacientes con antecedente de latigazo cervical y síntomas de vértigo e inestabilidad / Results of balance control and vestibular function tests in 51 patients with whiplash injury complaining of dizziness and imbalance

Introducción y objetivos. El vértigo y la inestabilidad tienen una importante implicación médico-legal en el paciente con antecedente de latigazo cervical (LC). En estos casos la posturografía dinámica computarizada (PDC) aporta información adicional a las pruebas vestibulares estándar y tiene descritos patrones compatibles con escasa colaboración o falta de sinceridad al esfuerzo, también denominados afisiológicos. El objetivo de este trabajo es valorar las características de las pruebas de equilibrio y función vestibular en pacientes con LC y especialmente, los resultados afisiológicos. Material y métodos. Estudio retrospectivo de pacientes con antecedente de LC con vértigo y/o inestabilidad. Se realizó videonistagmografía (VNG) y PDC. Los resultados de la prueba de organización sensorial (SOT) se valoraron como normales, vestibulares o afisiológicos usando el método de cálculo publicado por Cevette et al. en 1995. Resultados. Cincuenta y uno pacientes (24 varones, 27 mujeres); edad media: 42,2 años; tiempo de evolución medio: 3,8 m; PDC afisiológica: 13 (25,5%); PDC vestibular: 9 (17,6%); PDC normal: 29 (56,9%); VNG normal: 29 (56,9%); VNG alterada: 22 (43,1%); VNG vestibular: (n=11); VNG central: (n=6), y VNG cervical: (n=5). En el 46,2% de pacientes con PDC afisológica la VNG estaba alterada. Conclusiones. La prevalencia de pruebas afisiológicas en la PDC en el LC es relativamente elevada sin que deba suponerse simulación o exageración ya que en muchos casos existen signos objetivos de disfunción vestibular. Sería recomendable realizar pruebas de función vestibular a los pacientes con LC con síntomas vertiginosos. La rehabilitación vestibular podría ser de utilidad en estos casos (AU)

Introduction. The medical legal implications of dizziness and imbalance among patients with whiplash-associated disorders (WAD) are important. In these cases, Computerized Dynamic Posturography (CDP) provides information to standard vestibular tests and patterns consistent with scarce collaboration or lack of sincerity on efforts have been described. Objectives. This work has aimed to assess the prevalence of altered balance and vestibular function tests in patients with whiplash injury, and especially the aphysiologic results. Material and methods. A retrospective review of patients with whiplash injury referred for assessment of dizziness and/or imbalance was carried out. Standard videonistagmophgraphy (VNG) assessment including CDP was performed in all patients. The Sensory Organization Test (SOT) summaries were scored as normal, aphysiologic, or vestibular using the scoring method published by Cevette et al. in 1995. Results. The study included 51 patients (24 men, 27 women) with mean age: 42.2 years. Mean evolution time was 3.8 m. Aphysiologic CDP 13 (25.5%); vestibular CDP 9 (17.6%); normal CDP 29 (56.9%). Normal VNG 29 (56.9%); altered VNG in 22 (43.1%): vestibular VNG (n=11); central VNG (n=6); cervical VNG (n=5). VNG was altered in 46.2% of patients with aphysiologic CDP. Conclusions. The prevalence of aphysiologic results on CDP among whiplash injury patients is relatively high, however, this should not necessarily be consider to be related to malingering or exaggeration since objective signs of vestibular dysfunction are found in many cases. Thus, we recommend these tests should be done in whiplash injury patients complaining of dizziness and imbalance. Vestibular rehabilitation could be of interest in the recovery of these patients (AU)

Effects of hydrostatic pressure on the quaternary structure and enzymatic activity of a large peptidase complex from Pyrococcus horikoshii.

While molecular adaptation to high temperature has been extensively studied, the effect of hydrostatic pressure on protein structure and enzymatic activity is still poorly understood. We have studied the influence of pressure on both the quaternary structure and enzymatic activity of the dodecameric TET3 peptidase from Pyrococcus horikoshii. Small angle X-ray scattering (SAXS) revealed a high robustness of the oligomer under high pressure of up to 300 MPa at 25°C as well as at 90°C. The enzymatic activity of TET3 was enhanced by pressure up to 180 MPa. From the pressure behavior of the different rate-constants we have determined the volume changes associated with substrate binding and catalysis. Based on these results we propose that a change in the rate-limiting step occurs around 180 MPa.

Differential clinical characteristics and outcome predictors of acute heart failure in elderly patients.

OBJECTIVE: We determined the clinical-epidemiological characteristics and prognostic factors of early mortality and re-consultation in an elderly population attending the hospital emergency department (HED) for acute heart failure (AHF). PATIENTS AND METHODS: A prospective, observational, non interventional study including all the patients with AHF attended in the Spanish's HED. Two groups were defined: elderly (≥ 80 years) and controls (< 80 years). VARIABLES: demographic characteristics, comorbidity, degree of cardiac involvement, previous treatment, symptoms and signs of the AHF episode, precipitating factors, treatment in the HED and outcome. OUTCOME VARIABLES: mortality and re-consultation within 30 days. RESULTS: Of the 942 patients included, 455 of whom were elderly (48.3%). In this elderly population female sex, auricular fibrillation and a history of ictus and a poor functional status predominated. The type of ventricular dysfunction was unknown in 70%. No main differences in the presentation of AHF were found between the two groups. Mortality and re-consultation to the HED within 30 days were similar in both groups. While several factors were identified to be related to mortality or re-consultation in control group, in the elderly group it was more difficult to identify patients who will die or re-consult to the HED within the following 30 days. Only respiratory insufficiency on arrival to the HED was found to predict a greater probability of death (OR 3.55; CI95% 1.39-9.11). CONCLUSIONS: AHF in elderly patients presents some differential characteristics and, most importantly, it is more difficult to identify which of these patients will die or re-consult in the short-term.