Prospective monitoring of a CD4(+) CD25(high) CD45RO(+) CD127(high) T cell population after first kidney transplantation following thymoglobulin or basiliximab induction

Introduction: Recent data have suggested that a population of CD4+ CD25high T cells, phenotypically characterized by the expression of CD45RO and CD127, is significantly expanded in stable liver and kidney transplant recipients and represents alloreactive T cells. Induction therapies may have an impact on this alloreactive T cell population. In this study, we prospectively analyzed CD4+ CD25high CD45RO+ CD127high T cells after induction with either thymoglobulin or basiliximab. Patients & methods: A total of twenty-seven kidney transplant recipients were prospectively enrolled; 14 received thymoglobulin induction followed by a 4-day course of steroids with tacrolimus and mycophenolate mofetil ("thymo group"), and 13 received basiliximab induction followed by standard triple immunosuppression (tacrolimus, mycophenolate mofetil and prednisone) ("BSX group"). Phenotypical analysis by flow cytometry of the expression of CD25, CD45RO and CD127 on peripheral CD4+ T cells was performed at 0, 3 and 6 months after transplantation. Twenty-four healthy subjects (HS) were studied as controls. Results: There were no differences in baseline characteristics between the groups; at 6 months, patient survival (100%), graft survival (100%), serum creatinine (thymo versus BSX group: 129 versus 125 μmol/l) and acute rejection (2/14 versus 2/13) were not significantly different. Thymo induction produced a strong CD4 T cell depletion. As compared to pre-transplantation values, an expansion of the alloreactive T cell population was observed at 3 months in both thymo (mean: from 6.38% to 14.72%) and BSX (from 8.01% to 18.42%) groups. At 6 months, the alloreactive T cell population remained significantly expanded in the thymo group (16.92 ± 2.87%) whereas it tended to decrease in the BSX group (10.22 ± 1.38%). Conclusion: Overall, our results indicate that the expansion of alloreactive T cells occurs rapidly after transplantation in patients receiving either thymo or BSX induction. Whether differences at later timepoints or whether different IS regimens may modify this alloreactive population remains to be studied.

Activitat semipresencial a l'assignatura Clínica Odontològica Integrada Infantil (COII)

Un dels aspectes més importants en odontologia infantil és el control de la conducta, donat que sense la cooperació per part del nen resulta impossible realitzar qualsevol tractament dental. A l’assignatura COII, de cinquè curs de la llicenciatura d’Odontologia, hem optat per una metodologia semipresencial per tal que els alumnes siguin competents en relacionar-se amb el pacient infantil i els seus pares o tutors per permetre una execució eficaç del tractament.

El Sentit de l'humor en els infants : una breu aproximació des de la psicologia cognitiva

Darrerament hem investigat l’emergència del metallenguatge en els infants en contextos d’interaccions comunicatives naturals (Ivern, 2006) i hem establert un sistema de categories metalingüístiques per tal d’identifi car i conceptualitzar aquells comportaments relacionats amb la refl exió sobre el llenguatge, tot emmarcat en una perspectiva evolutiva. Els participants han estat 32 infants, 16 nens i 16 nenes, d’edats compreses entre els 2 anys i 8 mesos i els 8 anys, tots ells de parla castellana. Entre altres aspectes hem analitzat les funcions que compleix, atenent especialment a la relació tripartida entre metallenguatge, metacognició i recursivitat. En darrer terme, ens ha semblat interessant analitzar la relació del metallenguatge amb la teoria de la ment i el sentit de l’humor. La naturalesa metalingüística de l’humor ha estat estudiada des de principis dels anys setanta (Shultz, 1974 i Cazden, 1976) fi ns l’actualitat (Puche, 2001; Puche i Lozano, 2002). Bona part de l’nterès que ha desvetllat és per la seva importància com a indicador de l’activitat cognitiva. A continuació exposem una refl exió breu sobre el paper que juga el sentit de l’humor en els infants des de la perspectiva de la psicologia cognitiva.

Anticonvulsants in the treatment of aggression in the demented elderly: an update

Complex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity. METHODS: Commonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate. RESULTS: To date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate. CONCLUSION: So far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Incidence of Infectious Complications in Kidney Transplant Recipients Receiving Induction with Basiliximab, Thymoglobulin or Both

Background: The possible additional risk of infection in patients receiving induction with both basiliximab (Ba) and thymoglobulin (Th) is unclear. We assessed the 1-year incidence of infectious complications in 3 groups of kidney transplant recipients according to the type of induction therapy received.Methods: We compared the incidence of infection at 1 year in 3 groups of patients at our institution: fi rst transplant recipients received Ba 20mg at days 0 and 4 (Group Ba); in case of retransplantation or if PRA was >20% patients received Th 1 mg/kg for 3-5 days (Group Th); in case of delayed graft function (DGF), Ba was discontinued and Th was initiated (Group Ba+Th) or prolonged in Group Th. Kaplan-Meier curves were used to calculate the incidence of infection. A Cox analysis was used to identify risk factors for the development of infection.Results: Over 5 years, 170 consecutive kidney transplant recipients were performed:n=113 in Group Ba, n=39 in Group Th and n=18 in Group Ba+Th. As expected, more patients in Group Th received a second transplant (p<0.001). No differences in CMV serostatus were observed between groups (p=0.9). Incidences of CMV infection, CMV disease, BK viremia, BK nephropathy and urinary tract infection (UTI) is shown in Table 1. Table 1 Group Ba (n=113) Group Th (n=38) Group Ba+Th (n=18) CMV infection 31 (27%) 20 (51%) 8 (44%) CMV disease 7 (6%) 4 (10%) 0 BK viremia 11 (8%) 5 (13%) 4 (22%) BK nephropathy 5 (4%) 1 (2%) 2 (11%) UTI 43 (38%) 23 (59%) 6 (33%) Incidences of infection according to type of induction In a multivariate model taking into account CMV serostatus, age, pretransplant dialysis, type of organ transplanted, number of transplants and type of induction, Group Ba carried a lower risk of CMV infection (OR 0.45, p=0.006), and UTI (OR=0.6, p=0.05), but there were no differences in CMV disease (p=0.38). There was a trend towards higher incidence of BK viremia, but not nephropathy in Group Ba+Th (OR 2.2, p=0.23). There were no signifi cant differences in kidney function or graft loss at 1 year between groups.Conclusion: By multivariate analysis, we observed a lower risk of CMV infection andUTI in patients receiving Ba. The group Ba+Th had a similar risk for infection than the group receiving Th alone. Larger studies are needed to clarify whether combining Ba+Th in the setting of DGF may increase the risk of infectious complications, in particular BK infection.

Gene transfer of a soluble IL-1 type 2 receptor-Ig fusion protein improves cardiac allograft survival in rats.

OBJECTIVE: Interleukin-1 (IL-1) mediates ischemia-reperfusion injury and graft inflammation after heart transplantation. IL-1 affects target cells through two distinct types of transmembrane receptors, type-1 receptor (IL-1R1), which transduces the signal, and the non-signaling type-2 receptor (IL-1R2), which acts as a ligand sink that subtracts IL-1beta from IL-1R1. We analyzed the efficacy of adenovirus (Ad)-mediated gene transfer of a soluble IL-1R2-Ig fusion protein in delaying cardiac allograft rejection and the mechanisms underlying the protective effect. METHODS: IL-1 inhibition by IL-1R2-Ig was tested using an in vitro functional assay whereby endothelial cells preincubated with AdIL-1R2-Ig or control virus were stimulated with recombinant IL-1beta or tumor necrosis factor-alpha (TNF-alpha), and urokinase-type plasminogen activator (u-PA) induction was measured by zymography. AdIL-1R2-Ig was delivered to F344 rat donor hearts ex vivo, which were placed in the abdominal position in LEW hosts. Intragraft inflammatory cell infiltrates and proinflammatory cytokine expression were analyzed by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: IL-1R2-Ig specifically inhibited IL-1beta-induced u-PA responses in vitro. IL-1R2-Ig gene transfer reduced intragraft monocytes/macrophages and CD4(+) cell infiltrates (p<0.05), TNF-alpha and transforming growth factor-beta (TGF-beta) expression (p<0.05), and prolonged graft survival (15.6+/-5.7 vs 10.3+/-2.5 days with control vector and 10.1+/-2.1 days with buffer alone; p<0.01). AdIL-1R2-Ig combined with a subtherapeutic regimen of cyclosporin A (CsA) was superior to CsA alone (19.4+/-3.0 vs 15.9+/-1.8 days; p<0.05). CONCLUSIONS: Soluble IL-1 type-2 receptor gene transfer attenuates cardiac allograft rejection in a rat model. IL-1 inhibition may be useful as an adjuvant therapy in heart transplantation.

Technology educational affordance: Bridging the gap between patterns of interaction and technology usage

Peer-reviewed

A methodological approach to identify teacher's ICT competencies in online learning environments in Higher Education

Aquest article pretén descriure el procés metodològic d'identificació i mesurament de les competències TIC dels professors i com a formadors en les TIC en un entorn d'aprenentatge en línia en l'Educació Superior portat a terme en el marc del Projecte Europeu Elene-TLC.La revisió de la recerca en les competències en línia del professor demostra que, en primer lloc, el mètode més utilitzat per a identificar aquestes competències és el focus group. En segon lloc, la tècnica Delphi és la tècnica més utilitzada per reunir el consens d'experts sobre quines són les competències principals per al professor en línia entre els que s'indiquen.La proposta metodològica descrita en aquest document consisteix en la creació de 7 grups de discussió en línia, l'objectiu dels quals era identificar les competències formatives dels professors en línia i les dels professos en línia. La llista de competències obtingudes posteriorment es va oferir als experts europeus que participaven en l'aplicació de la tècnica Delphi. A aquests experts se'ls va demanar que ordenessin les competències d'acord amb el seu grau d'importància.Els resultats mostren que els grups de discussió en línia i el mètode Delphi són les metodologies apropiades per a identificar les competències TIC dels professors universitaris en els entorns d'aprenentatge en línia.

Delimitaciones previas a la formación para el uso de las TIC en la enseñanza universitaria: funciones y competencias del docente en entornos virtuales

En esta comunicación se esclarecen funciones, roles, competencias y tareas del docente universitario en entornos virtuales de enseñanza y aprendizaje con el propósito de contribuir a mejorar el diseño de acciones formativas dirigidas a la capacitación del profesorado para este ejercicio Este resultado se obtiene del análisis de significativas referencias que tratan el tema y de la valoración del diseño de acciones formativas realizadas en universidades europeas que participan activamente de este propósito. El estudio constituye una acción del proyecto Elene-TT - elearning network for Teacher Training.

Acute norovirus-induced agranulocytosis in a pediatric kidney transplant recipient.

Norovirus (NoV) infection is usually limited to the gastrointestinal (GI) tract. However, in immunocompromised patients, this infection might lead to severe life-threatening complications. We herein describe a pediatric kidney transplant patient who presented with an acute NoV infection complicated by febrile agranulocytosis that resolved with improvement of her GI illness. This unusual presentation has not been described before, to our knowledge. The aim of this article is to highlight the sometimes dramatic clinical presentation of NoV infection in immunosuppressed patients, and the importance of including this infection in the differential diagnosis of neutropenia in that specific population.

Estado del arte de la Planificación Colaborativa en la Cadena de Suministro: contexto determinista e incierto

En la economía actual, el resultado de las empresas depende en gran medida del éxito con el quese gestione la colaboración en su Cadena de Suministro (CdS). La globalización actual hapermitido a las empresas tener centros de almacenaje y distribución, propios o subcontratados,que pueden estar dispersos geográficamente y contar, al mismo tiempo, con proveedores en zonasalejadas provocando plazos de entrega más dilatados. La sincronización de los diversos agentesinvolucrados en la CdS, así como la relación que pueden establecer entre ellos requiere unaPlanificación Colaborativa entre los diferentes agentes con el fin de trabajar coordinados parapoder satisfacer las exigencias de un mercado cada vez más competitivo. En este trabajo deinvestigación se revisa y se clasifica la literatura referente a la planificación colaborativa de la CdS

Programación de la producción en un sistema flow shop híbrido sin esperas y tiempos de preparación dependientes de la secuencia.

Se estudia la programación de la producción en sistemas flow shop híbrido con tiempos depreparación dependientes de la secuencia de piezas a fabricar. Las piezas pueden pertenecer adiferentes familias y las máquinas requerirán un tiempo de preparación cada vez que se debacambiar de familia. Se han desarrollado procedimientos heurísticos para el caso monocriterio enel que el objetivo buscado en la programación de la producción es la minimización del retrasomedio, equivalente a minimizar la suma de retrasos de las piezas, y para el caso bicriterio en elque se tendrá en cuenta tanto la minimización de una función objetivo formada por la sumaponderada del retraso medio más la suma de los tiempos medios de proceso. Además se hanadaptado los métodos implementados para trabajar bajo la restricción nowait.