Infection of mice by the enteroaggregative E. coli strain 042 and two mutant derivatives overexpressing virulence factors: impact on disease markers, gut microbiota and concentration of SCFAs in feces.

Several pathogenic Escherichia coli strains cause diarrhea. Enteroaggregative E. coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC cells form a "stacked-brick" arrangement over the intestinal epithelial cells. EAEC isolates express, among other virulence determinants, the AggR transcriptional activator and the aggregative adherence fimbriae (AAF). Overexpression of the aggR gene results in increased expression of virulence factors such as the aff genes, as well as several genes involved in specific metabolic pathways such as fatty acid degradation (fad) and arginine degradation (ast). To support the hypothesis that induction of the expression of some of these pathways may play a role in EAEC virulence, in this study we used a murine infection model to evaluate the impact of the expression of these pathways on infection parameters. Mice infected with a mutant derivative of the EAEC strain 042, characterized by overexpression of the aggR gene, showed increased disease symptoms compared to those exhibited by mice infected with the wild type (wt) strain 042. Several of these symptoms were not increased when the infecting mutant, which overexpressed aggR, lacked the fad and ast pathways. Therefore, our results support the hypothesis that different metabolic pathways contribute to EAEC virulence.

Guía: Principios básicos de la neurorrehabilitación del paciente con daño cerebral adquirido. Recomendaciones de la Sociedad Española de Neurorrehabilitación / Guidelines: Basic principles of neurorehabilitation for patients with acquired brain injury. Recommendations of the Spanish Society of Neurorehabilitation

Introducción: Guía para la práctica clínica en neurorrehabilitación de personas adultas con daño cerebral adquirido de la Sociedad Española de Neurorrehabilitación. Documento basado en la revisión de guías de práctica clínica internacionales publicadas entre 2013-2020. Desarrollo: Se establecen recomendaciones según el nivel de evidencia que ofrecen los estudios revisados referentes a aspectos consensuados entre expertos dirigidos a definir la población, características específicas de la intervención o la exposición bajo investigación. Conclusiones: Deben recibir neurorrehabilitación todos aquellos pacientes que, tras un daño cerebral adquirido, hayan alcanzado una mínima estabilidad clínica. La neurorrehabilitación debe ofrecer tanto tratamiento como sea posible en términos de frecuencia, duración e intensidad (al menos 45-60 minutos de cada modalidad de terapia específica que el paciente precise). La neurorrehabilitación requiere un equipo transdisciplinar coordinado, con el conocimiento, la experiencia y las habilidades para trabajar en equipo tanto con pacientes como con sus familias. En la fase aguda, y para los casos más graves, se recomiendan programas de rehabilitación en unidades hospitalarias, procediéndose a tratamiento ambulatorio tan pronto como la situación clínica lo permita y se puedan mantener los criterios de intensidad. La duración del tratamiento debe basarse en la respuesta terapéutica y en las posibilidades de mejoría, en función del mayor grado de evidencia disponible. Al alta deben ofrecerse servicios de promoción de la salud, actividad física, apoyo y seguimiento para garantizar que se mantengan los beneficios alcanzados, detectar posibles complicaciones o valorar posibles cambios en la funcionalidad que hagan necesario el acceso a nuevos programas de tratamiento.(AU)

Introduction: We present the Spanish Society of Neurorehabilitation's guidelines for adult acquired brain injury (ABI) rehabilitation. These recommendations are based on a review of international clinical practice guidelines published between 2013 and 2020. Development: We establish recommendations based on the levels of evidence of the studies reviewed and expert consensus on population characteristics and the specific aspects of the intervention or procedure under research. Conclusions: All patients with ABI should receive neurorehabilitation therapy once they present a minimal level of clinical stability. Neurorehabilitation should offer as much treatment as possible in terms of frequency, duration, and intensity (at least 45–60 min of each specific form of therapy that is needed). Neurorehabilitation requires a coordinated, multidisciplinary team with the knowledge, experience, and skills needed to work in collaboration both with patients and with their families. Inpatient rehabilitation interventions are recommended for patients with more severe deficits and those in the acute phase, with outpatient treatment to be offered as soon as the patient's clinical situation allows it, as long as intensity criteria can be maintained. The duration of treatment should be based on treatment response and the possibilities for further improvement, according to the best available evidence. At discharge, patients should be offered health promotion, physical activity, support, and follow-up services to ensure that the benefits achieved are maintained, to detect possible complications, and to assess possible changes in functional status that may lead the patient to need other treatment programmes.(AU)

Guidelines: basic principles of neurorehabilitation for patients with acquired brain injury. Recommendations of the Spanish Society of Neurorehabilitation.

INTRODUCTION: We present the Spanish Society of Neurorehabilitation's guidelines for adult acquired brain injury (ABI) rehabilitation. These recommendations are based on a review of international clinical practice guidelines published between 2013 and 2020. DEVELOPMENT: We establish recommendations based on the levels of evidence of the studies reviewed and expert consensus on population characteristics and the specific aspects of the intervention or procedure under research. CONCLUSIONS: All patients with ABI should receive neurorehabilitation therapy once they present a minimal level of clinical stability. Neurorehabilitation should offer as much treatment as possible in terms of frequency, duration, and intensity (at least 45-60minutes of each specific form of therapy that is needed). Neurorehabilitation requires a coordinated, multidisciplinary team with the knowledge, experience, and skills needed to work in collaboration both with patients and with their families. Inpatient rehabilitation interventions are recommended for patients with more severe deficits and those in the acute phase, with outpatient treatment to be offered as soon as the patient's clinical situation allows it, as long as intensity criteria can be maintained. The duration of treatment should be based on treatment response and the possibilities for further improvement, according to the best available evidence. At discharge, patients should be offered health promotion, physical activity, support, and follow-up services to ensure that the benefits achieved are maintained, to detect possible complications, and to assess possible changes in functional status that may lead the patient to need other treatment programmes.

El impacto del nivel educativo en las valoraciones cognitivas de los pacientes jóvenes ingresados en rehabilitación tras un ictus isquémico / The impact of educational level on cognitive assessments in young patients admitted to rehabilitation after ischaemic stroke

Introducción y objetivo: Proponemos valorar el impacto del nivel educativo en las pruebas cognitivas al ingreso y al alta tras un periodo de rehabilitación cognitiva en los pacientes jóvenes tras un ictus isquémico. Materiales y métodos: Consideramos educación secundaria y superior (grupo A) y menos de 6 años de educación reglada (grupo B). Comparamos A y B mediante χ2 y Kruskal-Wallis. Estudiamos A y B como predictores de memoria verbal y de trabajo al alta. La memoria verbal y la memoria de trabajo las valoramos al ingreso y al alta mediante Rey Auditory Verbal Learning Test (RAVLT) y DIGITS del test Barcelona, espectivamente. Resultados: Analizamos n=277 pacientes (55% pertenecientes al grupo A, 51 años de edad media) ingresados a un centro especializado en España entre 2009 y 2019.Encontramos diferencias significativas (p<0,05) al ingreso, todas en favor del grupo A en las valoraciones de la atención, la inhibición, la visuopercepción, la visuoconstruccion, la fluencia verbal y la comprensión.En DIGITS y RAVLT-aprendizaje encontramos diferencias al ingreso. En DIGITS y RAVLT-reconocimiento encontramos diferencias al alta, todas en favor del grupo A. No encontramos diferencias en la edad, en la severidad, en el tiempo hasta el ingreso, ni en el tiempo de estadía ingresados.Tampoco encontramos diferencias en las ganancias cognitivas ni en la eficiencia del tratamiento en las pruebas de memoria.Los grupos A y B no predicen RAVLT (R2=0,53) ni DIGITS (R2=0,48). Conclusiones: El grupo A puntúa mejor en el 63% de las pruebas al ingreso y en el 75% de las pruebas al alta, los grupos A y B son similares en ganancias y eficiencia en las pruebas de memoria.(AU)

Introduction and objective: We propose to assess the impact of educational level on cognitive tests at admission and discharge after a period of cognitive rehabilitation in young patients after ischaemic stroke. Materials and methods: We considered secondary and higher education (group A) and less than 6 years of formal education (group B). We compared A and B using χ2 and Kruskal–Wallis. We studied A and B as predictors of verbal and working memory at discharge. Verbal and working memories were assessed at admission and discharge using Rey Auditory Verbal Learning Test (RAVLT) and DIGITS of the Barcelona Test respectively. Results: We analysed n=277 patients (55% belonging to A, mean age of 51 years) admitted to a specialised centre in Spain between 2009 and 2019.We found significant differences (P<.05) at admission, all in favour of A in the assessments of attention, inhibition, visuoperception, visuoconstruction, verbal fluency and comprehension.In DIGITS and RAVLT-learning we found differences at admission. In Digits and RAVLT-recognition we found differences at discharge, all in favour of A. We found no differences in age, severity, time at admission, or length of stay in hospital.Nor did we find differences in cognitive gains or treatment efficiency in memory tests.The groups A and B did not predict RAVLT (R2=.53) or DIGITS (R2=.48). Conclusions: A scores better in 63% of tests at admission and in 75% of tests at discharge, A and B are similar in gains and efficiency on memory tests.(AU)

Differential Expression of Two Copies of the irmA Gene in the Enteroaggregative E. coli Strain 042.

Gene duplications significantly impact the gene repertoires of both eukaryotic and prokaryotic microorganisms. The genomes of pathogenic Escherichia coli strains share a group of duplicated genes whose function is mostly unknown. The irmA gene is one of the duplicates encoded in several pathogenic E. coli strains. The function of its gene product was investigated in the uropathogenic E. coli strain CFT073, which contains a single functional copy. The IrmA protein structure mimics that of human interleukin receptors and likely plays a role during infection. The enteroaggregative E. coli strain 042 contains two functional copies of the irmA gene. In the present work, we investigated their biological roles. The irmA_4509 allele is expressed under several growth conditions. Its expression is modulated by the global regulators OxyR and Hha, with optimal expression at 37°C and under nutritional stress conditions. Expression of the irmA_2244 allele can only be detected when the irmA_4509 allele is knocked out. Differences in the promoter regions of both alleles account for their differential expression. Our results show that under several environmental conditions, the expression of the IrmA protein in strain 042 is dictated by the irmA_4509 allele. The irmA_2244 allele appears to play a backup role to ensure IrmA expression when the irmA_4509 allele loses its function. IMPORTANCE Gene duplications occur in prokaryotic genomes at a detectable frequency. In many instances, the biological function of the duplicates is unknown, and hence, the significance of the presence of multiple copies of these genes remains unclear. In pathogenic E. coli isolates, the irmA gene can be present either as a single copy or in two or more copies. We focused our work on studying why a different pathogenic E. coli strain encodes two functional copies of the irmA gene. We show that under several environmental conditions, one of the alleles dictates IrmA expression, and the second remains silent. The latter allele is only expressed when the former is silenced. The presence of more than one functional copy of the irmA gene in some pathogenic E. coli strains can result in sufficient expression of this virulence factor during the infection process.

Rehabilitación en régimen de ingreso en adultos en edad laboral tras un ictus isquémico: análisis clinicofuncional desde una perspectiva de género / Inpatient rehabilitation of working-age adults with ischemic stroke: comparing men and women clinical and functional characteristics at admission and predicting functionality

Introducción: El papel del género en la independencia funcional en las actividades de la vida diaria tras un ictus isquémico es aún controvertido. Proponemos: a) comparar características clínicas de hombres y mujeres en el momento del ingreso a rehabilitación hospitalaria; b) comparar su independencia funcional en el ingreso y en el alta, y c) identificar predictores de independencia funcional. Materiales y métodos: Estudio de cohortes retrospectivo observacional. Se incluyeron variables descritas en estudios previos en comparaciones ingreso-alta y en regresión lineal multivariante de la Functional Independence Measure (FIM) en el momento del alta, la ganancia, la eficiencia y la efectividad. Resultados: Se estudió a 144 pacientes (33%, mujeres) admitidos a rehabilitación en un centro español (= 3 semanas tras un ictus isquémico). Los hombres eran mayores (p = 0,003), un 19,6% diabéticos (un 6,4% de las mujeres; p = 0,03) y un 52,6% fumadores (un 72,3% de las mujeres; p = 0,02). No observamos diferencias significativas en la FIM en el momento del ingreso, del alta, la ganancia, la eficiencia ni la efectividad (FIM total, motora ni cognitiva). El análisis de regresión identificó el sexo (beta = –0,13), la gravedad (beta = –0,25) y la FIM total en el momento el ingreso (beta = –0,69) como predictores de la ganancia de la FIM total (R2 = 0,42). Las mismas variables predicen la FIM total en el alta: género (beta = –0,12), gravedad (beta = –0,23) y FIM total en el ingreso (beta = 0,59) (R2 = 0,51). La FIM en el ingreso (beta = –0,64), la gravedad (beta = –0,24), la edad (beta = –0,17) y el tiempo de estancia hospitalaria (beta = –0,45) predicen la eficiencia de la FIM total (R2 = 39,9). El modelo de efectividad de la FIM explica únicamente el 13,5% de la varianza. Conclusiones: No encontramos diferencias funcionales entre hombres y mujeres. El sexo es un predictor significativo, pero no explica la mitad de la varianza.(AU)

Introduction: The role of gender in functional independence for activities of daily living after ischemic stroke is still controversial. We aim to a) compare clinical characteristics of men and women at inpatient rehabilitation admission b) compare their functional independence at admission and discharge c) identify predictors of functional independence. Materials and methods: Retrospective observational cohort study. State-of-the-art variables were used for admission and discharge comparisons and to predict total FIM (Functional Independence Measure) at discharge, FIM gain, FIM efficiency and FIM effectiveness using multivariate linear regressions. Results: 144 patients (33% women) admitted to inpatient rehabilitation in a Spanish specialized center, with less than 3 weeks since ischemic stroke onset were included. Men were older (p = 0.039), 19.6% of men had diabetes mellitus (6.4% of women) (p = 0.038), with 52.6% of men being non-smokers (72.3% of women) (p = 0.022). No significant differences were observed in FIM at admission, discharge, FIM gain, efficiency or effectiveness (total, motor either cognitive FIM). Regression analysis identified sex (b = –0.13), stroke severity (b = –0.25) and admission total FIM (b = –0.69) as significant predictors of total FIM gain (R2 = 0.42). The same variables predicted discharge total FIM: sex (b = –0.12), severity (b = –0.23) and admission total FIM (b = 0.59) (R2 = 0.51). FIM efficiency was predicted by admission total FIM (b = –0.64), severity (b = –0.24), age (b = –0.17) and length of stay (b = –0.45) (R2 = 39.9%). FIM effectiveness model explained only 13.5% of the variance. Conclusions: No functional differences between men and women in any independence measure were found. Sex was a significant predictor but leaving half of the variance unexplained.(AU)

Inpatient rehabilitation of working-age adults with ischemic stroke: comparing men and women clinical and functional characteristics at admission and predicting functionality. / Rehabilitación en régimen de ingreso en adultos en edad laboral tras un ictus isquémico: análisis clinicofuncional desde una perspectiva de género.

INTRODUCTION: The role of gender in functional independence for activities of daily living after ischemic stroke is still controversial. We aim to a) compare clinical characteristics of men and women at inpatient rehabilitation admission b) compare their functional independence at admission and discharge c) identify predictors of functional independence. MATERIALS AND METHODS: Retrospective observational cohort study. State-of-the-art variables were used for admission and discharge comparisons and to predict total FIM (Functional Independence Measure) at discharge, FIM gain, FIM efficiency and FIM effectiveness using multivariate linear regressions. RESULTS: 144 patients (33% women) admitted to inpatient rehabilitation in a Spanish specialized center, with less than 3 weeks since ischemic stroke onset were included. Men were older (p = 0.039), 19.6% of men had diabetes mellitus (6.4% of women) (p = 0.038), with 52.6% of men being non-smokers (72.3% of women) (p = 0.022). No significant differences were observed in FIM at admission, discharge, FIM gain, efficiency or effectiveness (total, motor either cognitive FIM). Regression analysis identified sex (ß = -0.13), stroke severity (ß = -0.25) and admission total FIM (ß = -0.69) as significant predictors of total FIM gain (R2 = 0.42). The same variables predicted discharge total FIM: sex (ß = -0.12), severity (ß = -0.23) and admission total FIM (ß = 0.59) (R2 = 0.51). FIM efficiency was predicted by admission total FIM (ß = -0.64), severity (ß = -0.24), age (ß = -0.17) and length of stay (ß = -0.45) (R2 = 39.9%). FIM effectiveness model explained only 13.5% of the variance. CONCLUSIONS: No functional differences between men and women in any independence measure were found. Sex was a significant predictor but leaving half of the variance unexplained.

TITLE: Rehabilitación en régimen de ingreso en adultos en edad laboral tras un ictus isquémico: análisis clinicofuncional desde una perspectiva de género.Introducción. El papel del género en la independencia funcional en las actividades de la vida diaria tras un ictus isquémico es aún controvertido. Proponemos: a) comparar características clínicas de hombres y mujeres en el momento del ingreso a rehabilitación hospitalaria; b) comparar su independencia funcional en el ingreso y en el alta, y c) identificar predictores de independencia funcional. Materiales y métodos. Estudio de cohortes retrospectivo observacional. Se incluyeron variables descritas en estudios previos en comparaciones ingreso-alta y en regresión lineal multivariante de la Functional Independence Measure (FIM) en el momento del alta, la ganancia, la eficiencia y la efectividad. Resultados. Se estudió a 144 pacientes (33%, mujeres) admitidos a rehabilitación en un centro español (= 3 semanas tras un ictus isquémico). Los hombres eran mayores (p = 0,003), un 19,6% diabéticos (un 6,4% de las mujeres; p = 0,03) y un 52,6% fumadores (un 72,3% de las mujeres; p = 0,02). No observamos diferencias significativas en la FIM en el momento del ingreso, del alta, la ganancia, la eficiencia ni la efectividad (FIM total, motora ni cognitiva). El análisis de regresión identificó el sexo (beta = ­0,13), la gravedad (beta = ­0,25) y la FIM total en el momento el ingreso (beta = ­0,69) como predictores de la ganancia de la FIM total (R2 = 0,42). Las mismas variables predicen la FIM total en el alta: género (beta = ­0,12), gravedad (beta = ­0,23) y FIM total en el ingreso (beta = 0,59) (R2 = 0,51). La FIM en el ingreso (beta = ­0,64), la gravedad (beta = ­0,24), la edad (beta = ­0,17) y el tiempo de estancia hospitalaria (beta = ­0,45) predicen la eficiencia de la FIM total (R2 = 39,9). El modelo de efectividad de la FIM explica únicamente el 13,5% de la varianza. Conclusiones. No encontramos diferencias funcionales entre hombres y mujeres. El sexo es un predictor significativo, pero no explica la mitad de la varianza.

[The impact of educational level on cognitive assessments in young patients admitted to rehabilitation after ischaemic stroke]. / El impacto del nivel educativo en las valoraciones cognitivas de los pacientes jóvenes ingresados en rehabilitación tras un ictus isquémico.

INTRODUCTION AND OBJECTIVE: We propose to assess the impact of educational level on cognitive tests at admission and discharge after a period of cognitive rehabilitation in young patients after ischaemic stroke. MATERIALS AND METHODS: We considered secondary and higher education (group A) and less than 6 years of formal education (group B). We compared A and B using χ2 and Kruskal-Wallis. We studied A and B as predictors of verbal and working memory at discharge. Verbal and working memories were assessed at admission and discharge using Rey Auditory Verbal Learning Test (RAVLT) and DIGITS of the Barcelona Test respectively. RESULTS: We analysed n=277 patients (55% belonging to A, mean age of 51 years) admitted to a specialised centre in Spain between 2009 and 2019. We found significant differences (P<.05) at admission, all in favour of A in the assessments of attention, inhibition, visuoperception, visuoconstruction, verbal fluency and comprehension. In DIGITS and RAVLT-learning we found differences at admission. In Digits and RAVLT-recognition we found differences at discharge, all in favour of A. We found no differences in age, severity, time at admission, or length of stay in hospital. Nor did we find differences in cognitive gains or treatment efficiency in memory tests. The groups A and B did not predict RAVLT (R2=.53) or DIGITS (R2=.48). CONCLUSIONS: A scores better in 63% of tests at admission and in 75% of tests at discharge, A and B are similar in gains and efficiency on memory tests.

Overexpression of the third H-NS paralogue H-NS2 compensates fitness loss in hns mutants of the enteroaggregative Escherichia coli strain 042.

Members of the H-NS protein family play a role both in the chromosome architecture and in the regulation of gene expression in bacteria. The genomes of the enterobacteria encode an H-NS paralogue, the StpA protein. StpA displays specific regulatory properties and provides a molecular backup for H-NS. Some enterobacteria also encode third H-NS paralogues. This is the case of the enteroaggregative E. coli (EAEC) strain 042, which encodes the hns, stpA and hns2 genes. We provide in this paper novel information about the role of the H-NS2 protein in strain 042. A C > T transition in the hns2 promoter leading to increased H-NS2 expression is readily selected in hns mutants. Increased H-NS2 expression partially compensates for H-NS loss. H-NS2 levels are critical for the strain 042 fitness. Under some circumstances, high H-NS2 expression levels dictated by the mutant hns2 promoter can be deleterious. The selection of T > C revertants or of clones harboring insertional inactivations of the hns2 gene can then occur. Temperature also plays a relevant role in the H-NS2 regulatory activity. At 37 °C, H-NS2 targets a subset of the H-NS repressed genes contributing to their silencing. When temperature drops to 25 °C, the repressory ability of H-NS2 is significantly reduced. At low temperature, H-NS plays the main repressory role.

Evolution of Bacterial Global Modulators: Role of a Novel H-NS Paralogue in the Enteroaggregative Escherichia coli Strain 042.

Bacterial genomes sometimes contain genes that code for homologues of global regulators, the function of which is unclear. In members of the family Enterobacteriaceae, cells express the global regulator H-NS and its paralogue StpA. In Escherichia coli, out of providing a molecular backup for H-NS, the role of StpA is poorly characterized. The enteroaggregative E. coli strain 042 carries, in addition to the hns and stpA genes, a third gene encoding an hns paralogue (hns2). We present in this paper information about its biological function. Transcriptomic analysis has shown that the H-NS2 protein targets a subset of the genes targeted by H-NS. Genes targeted by H-NS2 correspond mainly with horizontally transferred (HGT) genes and are also targeted by the Hha protein, a fine-tuner of H-NS activity. Compared with H-NS, H-NS2 expression levels are lower. In addition, H-NS2 expression exhibits specific features: it is sensitive to the growth temperature and to the nature of the culture medium. This novel H-NS paralogue is widespread within the Enterobacteriaceae. IMPORTANCE Global regulators such as H-NS play key relevant roles enabling bacterial cells to adapt to a changing environment. H-NS modulates both core and horizontally transferred (HGT) genes, but the mechanism by which H-NS can differentially regulate these genes remains to be elucidated. There are several instances of bacterial cells carrying genes that encode homologues of the global regulators. The question is what the roles of these proteins are. We noticed that the enteroaggregative E. coli strain 042 carries a new hitherto uncharacterized copy of the hns gene. We decided to investigate why this pathogenic E. coli strain requires an extra H-NS paralogue, termed H-NS2. In our work, we show that H-NS2 displays specific expression and regulatory properties. H-NS2 targets a subset of H-NS-specific genes and may help to differentially modulate core and HGT genes by the H-NS cellular pool.

A functional microengineered model of the human splenon-on-a-chip.

The spleen is a secondary lymphoid organ specialized in the filtration of senescent, damaged, or infected red blood cells. This unique filtering capacity is largely due to blood microcirculation through filtration beds of the splenic red pulp in an open-slow microcirculation compartment where the hematocrit increases, facilitating the recognition and destruction of unhealthy red blood cells by specialized macrophages. Moreover, in sinusal spleens such as those of humans, blood in the open-slow microcirculation compartment has a unidirectional passage through interendothelial slits before reaching the venous system. This further physical constraint represents a second stringent test for erythrocytes ensuring elimination of those cells lacking deformability. With the aim of replicating the filtering function of the spleen on a chip, we have designed a novel microengineered device mimicking the hydrodynamic forces and the physical properties of the splenon, the minimal functional unit of the red pulp able to maintain filtering functions. In this biomimetic platform, we have evaluated the mechanical and physiological responses of the splenon using human red blood cells and malaria-infected cells. This novel device should facilitate future functional studies of the spleen in relation to malaria and other hematological disorders.

Flexible composition and execution of high performance, high fidelity multiscale biomedical simulations.

Multiscale simulations are essential in the biomedical domain to accurately model human physiology. We present a modular approach for designing, constructing and executing multiscale simulations on a wide range of resources, from laptops to petascale supercomputers, including combinations of these. Our work features two multiscale applications, in-stent restenosis and cerebrovascular bloodflow, which combine multiple existing single-scale applications to create a multiscale simulation. These applications can be efficiently coupled, deployed and executed on computers up to the largest (peta) scale, incurring a coupling overhead of 1-10% of the total execution time.

Do traditional executive measures tell us anything about daily-life functioning after traumatic brain injury in Spanish-speaking individuals?

PRIMARY OBJECTIVE: To examine the relationship between traditional executive function measures and everyday competence in Spanish-speaking individuals with moderate-to-severe traumatic brain injury (TBI). METHODS AND PROCEDURES: Thirty-two TBI patients (24 men, eight women) with an age range of 17-59 years (mean age = 30.73 years; SD = 13.34) were administered a battery of performance-based executive function measures. Such measures included the Trail Making Test part B, Wisconsin Card Sorting Test, Stroop Colour Word Interference Test, Controlled Oral Word Association Test and Letter-Number Sequencing. Behavioural manifestations of executive deficits were assessed by the Behaviour Rating Inventory of Executive Function-Adult version (BRIEF-A). Patient's everyday functioning was examined with the Patient Competency Rating Scale (PCRS). MAIN OUTCOMES AND RESULTS: Traditional performance-based executive measures correlated significantly, although moderately, with the PCRS; this relationship was more significant in the Controlled Oral Word Association Test and Trail Making Test part B. A significant correlation was obtained between the BRIEF-A clinical scales and patient's everyday competence as measured by the PCRS. CONCLUSIONS: The current findings suggest that traditional performance-based executive measures reveal some degree of ecological validity or real-world relevance, providing relevant information for predicting everyday competence after moderate-to-severe TBI.

Computational modelling of cardiac electrophysiology: explanation of the variability of results from different numerical solvers.

A recent verification study compared 11 large-scale cardiac electrophysiology solvers on an unambiguously defined common problem. An unexpected amount of variation was observed between the codes, including significant error in conduction velocity in the majority of the codes at certain spatial resolutions. In particular, the results of the six finite element codes varied considerably despite each using the same order of interpolation. In this present study, we compare various algorithms for cardiac electrophysiological simulation, which allows us to fully explain the differences between the solvers. We identify the use of mass lumping as the fundamental cause of the largest variations, specifically the combination of the commonly used techniques of mass lumping and operator splitting, which results in a slightly different form of mass lumping to that supported by theory and leads to increased numerical error. Other variations are explained through the manner in which the ionic current is interpolated. We also investigate the effect of different forms of mass lumping in various types of simulation.

Functional analysis of Plasmodium vivax VIR proteins reveals different subcellular localizations and cytoadherence to the ICAM-1 endothelial receptor.

The subcellular localization and function of variant subtelomeric multigene families in Plasmodium vivax remain vastly unknown. Among them, the vir superfamily is putatively involved in antigenic variation and in mediating adherence to endothelial receptors. In the absence of a continuous in vitro culture system for P. vivax, we have generated P. falciparum transgenic lines expressing VIR proteins to infer location and function. We chose three proteins pertaining to subfamilies A (VIR17), C (VIR14) and D (VIR10), with domains and secondary structures that predictably traffic these proteins to different subcellular compartments. Here, we showed that VIR17 remained inside the parasite and around merozoites, whereas VIR14 and VIR10 were exported to the membrane of infected red blood cells (iRBCs) in an apparent independent pathway of Maurer's clefts. Remarkably, VIR14 was exposed at the surface of iRBCs and mediated adherence to different endothelial receptors expressed in CHO cells under static conditions. Under physiological flow conditions, however, cytoadherence was only observed to ICAM-1, which was the only receptor whose adherence was specifically and significantly inhibited by antibodies against conserved motifs of VIR proteins. Immunofluorescence studies using these antibodies also showed different subcellular localizations of VIR proteins in P. vivax-infected reticulocytes from natural infections. These data suggest that VIR proteins are trafficked to different cellular compartments and functionally demonstrates that VIR proteins can specifically mediate cytoadherence to the ICAM-1 endothelial receptor.

fMRI of the sensorimotor cortex in patients with traumatic brain injury after intensive rehabilitation.

For evaluating the patterns of brain activation in sensorimotor areas following motor rehabilitation, seven male patients diagnosed with TBI underwent an fMRI study before and after being subjected to motor rehabilitation. Six patients showed a reduction in the BOLD signal of their motor cortical areas during the second fMRI evaluation. A decrease in cerebellum activation was also observed in two patients. Newly activated areas, were observed in four patients after treatment. In addition, an increase in the activation of the supplementary motor area (SMA) following rehabilitation was observed in only one test subject. The findings show that motor rehabilitation in TBI patients produces a decrease in the BOLD signal for the sensorimotor areas that were activated prior to treatment. In addition, we observed the recruitment of different brain areas to compensate for functional loss due to TBI in line with the cortical reorganisation mechanism.

Aplicación de la clasificación internacional del funcionamiento, de la discapacidad y de la salud en la evaluación del paciente con secuelas de traumatismo craneoencefálico / Applicability of the International Classification of Functioning, Disability and health in the evaluation of patients with traumatic brain injury

Introducción. El traumatismo craneoencefálico (TCE) es la causa más común de discapacidad en las primeras décadas de la vida y sus secuelas comprenden cambios motores, conductuales y cognitivos. Medir estos cambios es un aspecto esencial en la rehabilitación para identificar objetivos, cuantificar secuelas y crear planes de intervención. El objetivo de este estudio es evaluar la funcionalidad tras un programa de rehabilitación empleando la Clasificación Internacional de la Funcionalidad (CIF) como marco conceptual. Material y método. Se revisaron retrospectivamente los resultados funcionales de 77 pacientes con TCE grave según la escala FIM FAM expresados en la nomenclatura de la CIF siguiendo la metodología de las linking rules. Resultados. Sólo un 3,8% del total de la CIF se evalúa mediante la FIM FAM. Se pudo traducir la mayoría de los conceptos a la nomenclatura de la CIF, pero es notoria la ausencia de factores medioambientales. A nivel cognitivo, el deterioro fue máximo en las categorías de solución de problemas (81,8%), empleabilidad (77,9%) y juicio (77,9%). Subir escaleras (85,7%) y movilidad comunitaria (81,8%) fueron las más afectadas a nivel motor. Conclusiones. El uso de la CIF como marco conceptual permite describir el estado de salud de individuos como TCE y conceptualmente es capaz de detectar limitaciones como la ausencia de factores medioambientales(AU)

Introduction. Traumatic Brain Injury (TBI) is the leading cause of disability in the first decades of life. Motor, cognitive and behavioral changes are examples of its sequelae. The measurement of these changes are essential aspects of rehabilitation in order to identify objectives, quantify problems and plan interventions. The objective of this study is to evaluate functioning after a rehabilitation programme using the International Classification of Functioning (ICF) as a conceptual framework. Material and method. The outcome of 77 patients with severe TBI were retrospectively analyzed using the FIM FAM scale expressed in terms of ICF coding following the methodology of the «linking rules.» Results. Only 3.8% of the ICF are evaluated by the FIM FAM. Most of the concepts could translated into the ICF language. However, the lack of environmental factors stands out. The most affected cognitive areas were problem solving (81.8%), employability (77.9%) and judgment with a 77.9% of patients showing problem (4). Climbing stairs (85.7%) and Community mobility (81.8%) were the mostly affected motor functions. Conclusions. The use of ICF as a conceptual framework allows to describe the health status of a TBI patient and it is conceptually capable of detecting limitations such as a lack in evaluating environmental factors(AU)

Alteraciones conductuales e integración comunitaria en el traumatismo craneoencefálico moderado y grave / Behaviour disorders and community integration following moderate to severe traumatic brain injury

Introducción: Clínicos e investigadores argumentan que los cambios conductuales asociados al traumatismo craneoencefálico (TCE) tienen un impacto devastador en la calidad de vida del afectado. El objetivo de este estudio es examinar la relación entre las alteraciones conductuales y la integración comunitaria después de un TCE moderado o grave. Material y métodos: En este estudio retrospectivo participaron 90 personas con un TCE moderado o grave (rango de edad: 16–66 años; edad media: 29,7 años; DE: 14,7). El nivel de integración en la comunidad se valoró mediante el Community Integration Questionnaire y la presencia de alteraciones conductuales se valoró mediante un cuestionario creado ad hoc para la situación objeto de estudio. En función de las puntuaciones obtenidas en el cuestionario conductual los sujetos fueron divididos en dos grupos: pacientes con alteraciones conductuales (n=56) y pacientes sin alteraciones conductuales (n=34). Resultados: La prueba de Mann-Whitney reveló diferencias significativas entre ambos grupos en el nivel de integración comunitaria (p=0,002); los sujetos con alteraciones conductuales mostraron puntuaciones sensiblemente inferiores en el Community Integration Questionnaire. Conclusiones: Los resultados muestran la existencia de una relación entre la presencia de alteraciones conductuales y el nivel de integración comunitaria tras un TCE moderado o grave. Sin embargo, la direccionalidad de esta relación es confusa, limitando así nuestra capacidad para efectuar inferencias causales. Son necesarios futuros estudios que permitan entender la naturaleza de esta relación (AU)

Introduction: Clinicians and researchers argue that one of the most devastating impairments from traumatic brain injury (TBI) is behaviour change. The objective of this study was to examine the relationship between behaviour disorders and community integration following moderate to severe TBI. Material and methods: Ninety persons with moderate to severe TBI (age range: 16-66 years; mean age: 29.7 years; SD: 14.7) were included in this retrospective study. Subjects were administered the Community Integration Questionnaire (CIQ) to measure community integration and a questionnaire to assess behaviour disorders. Subjects were divided into two groups: TBI patients with behaviour disorders (n=56) and TBI patients without behaviour disorders (n=34). Results: Mann-Whitney tests revealed significant differences in community integration level between both groups (p=0,002); subjects with behaviour disorders had lower CIQ scores compared to subjects without behaviour disorders. Conclusions: Results show that there exist a relationship between behaviour disorders and community integration level following moderate to severe TBI. However, the directionality of this relationship remains unclear, limiting our ability to make causal inferences. Future research is needed to understand the nature of this relationship (AU)