[Prognostic factors and profile in traumatic brain injury in the paediatric age]. / Perfil y factores pronósticos en el traumatismo craneoencefálico en la edad pediátrica.

INTRODUCTION: Traumatic brain injury (TBI) is a common cause of death and disability in the paediatric population, although the literature on the Spanish population is scarce. From the perspective of early vulnerability, recent research findings suggest that early brain injury has worse sequelae and a higher risk of impact. AIMS: To analyse the intelligence profile, executive functions and behaviour, and examine the association between age at the time of the injury, severity of the TBI and environmental factors for cognitive and behavioural outcomes. PATIENTS AND METHODS: Seventy-one participants with moderate to severe TBI, from 6 to 16 years of age, were assessed with measures of intelligence (intelligence quotient), executive functions and behaviour. RESULTS: Children with TBI are at increased risk of disability in all aspects of intelligence, executive functions and behaviour. Children who suffered a traumatic brain injury in infancy and the preschool period had more overall effects on intelligence quotient and some aspects of the executive functions. CONCLUSIONS: Socioeconomic and cultural factors are the best predictors for intelligence quotient and behaviour. These findings contribute to a better understanding of the sequelae of TBI in children, which will help in rehabilitation planning and re-adaptation to functional life.

TITLE: Perfil y factores pronósticos en el traumatismo craneoencefálico en la edad pediátrica.Introducción. El traumatismo craneoencefálico (TCE) es una causa común de muerte y discapacidad en la población pediátrica, aunque la bibliografía en población española sea escasa. Desde la perspectiva de la vulnerabilidad temprana, los hallazgos de investigaciones recientes sugieren que la lesión cerebral temprana tiene peores secuelas y un mayor riesgo de impacto. Objetivos. Analizar el perfil de la inteligencia, las funciones ejecutivas y el comportamiento, y examinar la asociación de la edad a la lesión, la gravedad del TCE y los factores ambientales para los resultados cognitivos y conductuales. Pacientes y métodos. Setenta y un participantes con TCE moderado a grave, con edades entre 6 y 16 años, fueron evaluados con medidas de inteligencia (cociente intelectual), funciones ejecutivas y comportamiento. Resultados. Los niños con TCE tienen un mayor riesgo de discapacidad en todos los aspectos de inteligencia, funciones ejecutivas y comportamiento. Los niños que sufrieron una lesión cerebral traumática en la infancia y preescolar registraron más efectos globales en el cociente intelectual y algunos aspectos de las funciones ejecutivas. Conclusiones. Los factores socioeconómicos y culturales son los mejores predictores para el cociente intelectual y el comportamiento. Estos hallazgos contribuyen a una mejor comprensión de las secuelas de TCE en los niños para ayudar en la planificación de rehabilitación y la readaptación a la vida funcional.

Efficacy of a new parent and school-supported intervention after moderate and severe childhood traumatic brain injury. / Eficacia de una nueva intervencion de apoyo a padres y escuelas despues de un traumatismo craneoencefalico moderado o grave.

INTRODUCTION: Traumatic brain injury is a common cause of acquired disability during childhood. Early interventions focusing on parenting practices may prove effective at reducing negative child outcomes. AIM: To determine the efficacy of a new counselling program aimed at parents and schools compared to a control group. PATIENTS AND METHODS: The main study sample was obtained from a paediatric hospital. The final sample consisted of 42 children aged between 6 and 16 years old. RESULTS: Comparing with normative data, pre-post comparisons between groups showed a significant improvement in the parent group with respect to the control group. CONCLUSIONS: The superiority of the parental intervention group over those of the control group was not only statistically significant, but also clinically substantial and meaningful. The results of this study suggest that children with moderate to severe traumatic brain injury can benefit from an intensive supported family treatment.

TITLE: Eficacia de una nueva intervencion de apoyo a padres y escuelas despues de un traumatismo craneoencefalico moderado o grave.Introduccion. El traumatismo craneoencefalico es una causa habitual de discapacidad adquirida durante la infancia. Las intervenciones tempranas que se centran en la participacion de los padres pueden resultar efectivas para reducir las disfunciones del niño. Objetivo. Determinar la eficacia de un nuevo programa de asesoramiento dirigido a padres y escuelas en comparacion con un grupo control. Pacientes y metodos. La muestra principal del estudio se obtuvo de un hospital pediatrico. La muestra final consistio en 42 niños de 6 a 16 años. Resultados. Comparando con los datos normativos, las comparaciones pre y post intragrupos mostraron una mejora significativa en el grupo de intervencion parental con respecto al grupo control. Conclusiones. La superioridad del grupo de intervencion parental sobre el grupo control no solo fue estadisticamente significativa, sino tambien clinicamente sustancial y relevante. Los resultados del estudio sugieren que los niños con traumatismo craneoencefalico moderado o grave pueden beneficiarse de un tratamiento familiar intensivo de apoyo.

Occurrence of antibiotics and bacterial resistance in wastewater and sea water from the Antarctic.

The potential presence of introduced antibiotics in the aquatic environment is a hot topic of concern, particularly in the Antarctic, a highly vulnerable area protected under the Madrid protocol. The increasing presence of human population, especially during summer, might led to the appearance of pharmaceuticals in wastewater. The previous discovery of Escherichia coli strains resistant to antibiotics in sea water and wastewater collected in King George Island motivated our investigation on antibiotics occurrence in these samples. The application of a multi-residue LCMS/MS method for 20 antibiotics, revealed the presence of 8 compounds in treated wastewater, mainly the quinolones ciprofloxacin and norfloxacin (92% and 54% of the samples analyzed, average concentrations 0.89 µg/L and 0.75 µg/L, respectively) and the macrolides azithromycin and clarithromycin (15% positive samples, and average concentrations near 0.4 µg/L), and erythromycin (38% positive samples, average concentration 0.003 µg/L). Metronidazole and clindamycin were found in one sample, at 0.17 and 0.1 µg/L, respectively; and trimethoprim in two samples, at 0.001 µg/L. Analysis of sea water collected near the outfall of the wastewater discharges also showed the sporadic presence of 3 antibiotics (ciprofloxacin, clindamycin, trimethoprim) at low ng/L level, illustrating the impact of pharmaceuticals consumption and the poor removal of these compounds in conventional WWTPs. The most widespread antibiotic in sea water was ciprofloxacin, which was found in 15 out of 34 sea water samples analyzed, at concentrations ranging from 4 to 218 ng/L. Bacteria resistance was observed for some antibiotics identified in the samples (e.g. trimetropim and nalidixic acid -a first generation quinolone). However, resistance to some groups of antibiotics could not be correlated to their presence in the water samples due to analytical limitations (penicillins, tetraciclines). On the contrary, for some groups of antibiotics detected in samples (macrolides), the antibacterial activity against E. Coli was not investigated because these antibiotics do not include this bacterial species in their spectrum of activity. Our preliminary data demonstrate that antibiotics occurrence in the Antarctic aquatic environment is an issue that needs to be properly addressed. Periodical monitoring of water samples and the implementation of additional treatments in the WWTPs are recommended as a first step to prevent potential problems related to the presence of antibiotics and other emerging contaminants in the near future in Antarctica.

'An investigation into the occurrence and removal of pharmaceuticals in Colombian wastewater'.

In this work, the presence of 20 pharmaceuticals in wastewater from Colombia is investigated. Several widely consumed compounds have been detected in wastewater samples from different origins and geographical areas in Colombia. The studied pharmaceuticals included antibiotics, analgesics and anti-inflammatories, cholesterol lowering statin drugs, lipid regulators, and anti-depressants. The investigated samples were urban wastewater collected during one whole week before (influent) and after treatment (effluent) in the wastewater treatment plants (WWTPs) of Bogotá and Medellin. Raw wastewater from the Hospital of Tumaco and from the city of Florencia were also collected. Analyses performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that most of the target analytes were present in all the wastewater samples. The highest concentrations (up to 50 µg/L) corresponded to acetaminophen, but several antibiotics, such as azithromycin, ciprofloxacin and norfloxacin, and antihypertensive drugs, such as losartan and valsartan, were commonly present in influent wastewater (IWW) at levels above 1 µg/L. Moreover, the treatment applied in WWTPs seemed to not efficiently remove the compounds under study, because most pharmaceuticals were also present in effluent wastewater (EWW) at concentrations close to those of the IWW. Special emphasis was made in this work on the quality of data reported, performing a detailed study of quality control (QC) samples. The analytical approach used -direct injection of 5-fold diluted samples without any additional treatment - is simpler and faster than the commonly applied solid phase extraction (SPE). The use of 12 isotope-labelled internal standards ensured the satisfactory correction of matrix effects for the corresponding analytes. For the remaining 8 compounds, no drastic matrix effects were observed, and only four compounds (cloxacillin, doxycycline, losartan, tetracycline) presented QC recoveries near or slightly below 60%, revealing ionization suppression, particularly in the IWW. Data on the occurrence of pharmaceuticals reported in this paper are the basis for current studies that aim to develop efficient systems for the degradation/removal of these compounds from the aquatic environment.

CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair.

In genome editing with CRISPR-Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integration by HDR at the human AAVS1 safe harbor locus. A minimal N-terminal fragment of CtIP, designated HE for HDR enhancer, is sufficient to stimulate HDR and this depends on CDK phosphorylation sites and the multimerization domain essential for CtIP activity in homologous recombination. HDR stimulation by Cas9-HE, however, depends on the guide RNA used, a limitation that may be overcome by testing multiple guides to the locus of interest. The Cas9-HE fusion is simple to use and allows obtaining twofold or more efficient transgene integration than that with Cas9 in several experimental systems, including human cell lines, iPS cells, and rat zygotes.

The classification of almonds (Prunus dulcis) by country and variety using UHPLC-HRMS-based untargeted metabolomics.

The aim of this study was to use an untargeted UHPLC-HRMS-based metabolomics approach allowing discrimination between almonds based on their origin and variety. Samples were homogenised, extracted with ACN:H2O (80:20) containing 0.1% HCOOH and injected in a UHPLC-QTOF instrument in both positive and negative ionisation modes. Principal component analysis (PCA) was performed to ensure the absence of outliers. Partial least squares - discriminant analysis (PLS-DA) was employed to create and validate the models for country (with five different compounds) and variety (with 20 features), showing more than 95% accuracy. Additional samples were injected and the model was evaluated with blind samples, with more than 95% of samples being correctly classified using both models. MS/MS experiments were carried out to tentatively elucidate the highlighted marker compounds (pyranosides, peptides or amino acids, among others). This study has shown the potential of high-resolution mass spectrometry to perform and validate classification models, also providing information concerning the identification of the unexpected biomarkers which showed the highest discriminant power.

UHPLC-QTOF MS screening of pharmaceuticals and their metabolites in treated wastewater samples from Athens.

After consumption, pharmaceuticals are excreted as parent compounds and/or metabolites in urine and faeces. Some are not completely removed during wastewater treatments, forcing sewage treatment plants (STPs) to apply alternative technologies to guarantee quality of treated water. To monitor the removal efficiency of STPs, not only unchanged compounds and metabolites have to be taken into account, but also formation of possible transformation products (TPs). In this work, QTOF MS has been used for screening metabolites/TPs of pharmaceuticals in effluent wastewater from Athens. A customised database was built with the exact masses of metabolites reported in literature for the parent drugs found in an initial screening. Additionally, TPs identified in previous degradation experiments performed at our laboratory were included. Up to 34 metabolites/TPs were detected for omeprazole, venlafaxine, clindamycin, clarithromycin, clopidogrel or dipyrone, among others. Seven corresponded to TPs whose reference standards were available at our lab, seven were TPs previously identified in laboratory degradation experiments, eight were TPs tentatively identified by QTOF MS without reference standards, and twelve TPs were discovered after using the common fragmentation pathway approach. Tentative identification of TPs was supported by prediction of their chromatographic retention time based on the use of advanced chemometric QSRR models.

Behaviour of emerging contaminants in sewage sludge after anaerobic digestion.

Nowadays, there is an increasing concern over the presence of contaminants in the aquatic environment, where they can be introduced from wastewater after their incomplete removal in the treatment plants. In this work, degradation of selected emerging pollutants in the aqueous and solid phases of sewage sludge has been investigated after anaerobic digestion using two different digesters: mesophilic and thermophilic. Initially, sludge samples were screened by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) for identification of emerging contaminants in the samples. In a second step, a target quantitative method based on LC coupled to tandem MS was applied for selected pollutants identified in the previous screening. The behaviour of the compounds under anaerobic conditions was studied estimating the degradation efficiency and distribution of compounds between both sludge phases. Irbesartan and benzoylecgonine seemed to be notably degraded in both phases of the sludge. Venlafaxine showed a significant concentration decrease in the aqueous phase in parallel to an increase in the solid phase. The majority of the compounds showed an increase of their concentrations in both phases after the digestion. Concentrations in the solid phase were commonly higher than in the aqueous for most contaminants, indicating that they were preferentially adsorbed onto the solid particles.

Analytical methodologies based on LC-MS/MS for monitoring selected emerging compounds in liquid and solid phases of the sewage sludge.

In this work, two analytical methodologies based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were developed for quantification of emerging pollutants identified in sewage sludge after a previous wide-scope screening. The target list included 13 emerging contaminants (EC): thiabendazole, acesulfame, fenofibric acid, valsartan, irbesartan, salicylic acid, diclofenac, carbamazepine, 4-aminoantipyrine (4-AA), 4-acetyl aminoantipyrine (4-AAA), 4-formyl aminoantipyrine (4-FAA), venlafaxine and benzoylecgonine. The aqueous and solid phases of the sewage sludge were analyzed making use of Solid-Phase Extraction (SPE) and UltraSonic Extraction (USE) for sample treatment, respectively. The methods were validated at three concentration levels: 0.2, 2 and 20 µg L(-1) for the aqueous phase, and 50, 500 and 2000 µg kg(-1) for the solid phase of the sludge. In general, the method was satisfactorily validated, showing good recoveries (70-120%) and precision (RSD < 20%). Regarding the limit of quantification (LOQ), it was below 0.1 µg L(-1) in the aqueous phase and below 50 µg kg(-1) in the solid phase for the majority of the analytes. The method applicability was tested by analysis of samples from a wider study on degradation of emerging pollutants in sewage sludge under anaerobic digestion. The key benefits of these methodologies are: • SPE and USE are appropriate sample procedures to extract selected emerging contaminants from the aqueous phase of the sewage sludge and the solid residue. • LC-MS/MS is highly suitable for determining emerging contaminants in both sludge phases. • Up to our knowledge, the main metabolites of dipyrone had not been studied before in sewage sludge.

Identification of new omeprazole metabolites in wastewaters and surface waters.

Omeprazole is one of the world-wide most consumed pharmaceuticals for treatment of gastric diseases. As opposed to other frequently used pharmaceuticals, omeprazole is scarcely detected in urban wastewaters and environmental waters. This was corroborated in a previous research, where parent omeprazole was not detected while four transformation products (TPs), mainly resulting from hydrolysis, were found in effluent wastewaters and surface waters. However, the low abundance of omeprazole TPs in the water samples together with the fact that omeprazole suffers an extensive metabolism, with a wide range of excretion rates (between 0.01 and 30%), suggests that human urinary metabolites should be investigated in the water environment. In this work, the results obtained in excretion tests after administration of a 40 mg omeprazole dose in three healthy volunteers are reported. Analysis by liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS) reported low concentrations of omeprazole in urine. Up to twenty-four omeprazole metabolites (OMs) were detected and tentatively elucidated. The most relevant OM was an omeprazole isomer, which obviously presented the same exact mass (m/z 346.1225), but also shared a major common fragment at m/z 198.0589. Subsequent analyses of surface water and effluent wastewater samples by both LC-QTOF MS and LC-MS/MS with triple quadrupole revealed that this metabolite (named as OM10) was the compound most frequently detected in water samples, followed by OM14a and OM14b. Up to our knowledge, OM10 had not been used before as urinary biomarker of omeprazole in waters. On the contrary, parent omeprazole was never detected in any of the water samples. After this research, it seems clear that monitoring the presence of omeprazole in the aquatic environment should be focused on the OMs suggested in this article instead of the parent compound.

Investigating the presence of omeprazole in waters by liquid chromatography coupled to low and high resolution mass spectrometry: degradation experiments.

Omeprazole is one of the most consumed pharmaceuticals around the world. However, this compound is scarcely detected in urban wastewater and surface water. The absence of this pharmaceutical in the aquatic ecosystem might be due to its degradation in wastewater treatment plants, as well as in receiving water. In this work, different laboratory-controlled degradation experiments have been carried out on surface water in order to elucidate generated omeprazole transformation products (TPs). Surface water spiked with omeprazole was subjected to hydrolysis, photo-degradation under both sunlight and ultraviolet radiation and chlorination. Analyses by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF MS) permitted identification of up to 17 omeprazole TPs. In a subsequent step, the TPs identified were sought in surface water and urban wastewater by LC-QTOF MS and by LC coupled to tandem mass spectrometry with triple quadrupole. The parent omeprazole was not detected in any of the samples, but four TPs were found in several water samples. The most frequently detected compound was OTP 5 (omeprazole sulfide), which might be a reasonable candidate to be included in monitoring programs rather than the parent omeprazole.

Perfil neuropsicológico de niños adoptados internacionalmente en Cataluña / Neuropsychological profile of internationally adopted children in Catalonia

Introducción: En los últimos años la adopción internacional ha aumentado considerablemente en nuestro país. China, Federación Rusa, Colombia y Etiopía suponen el 77% del total de las adopciones internacionales en España. Los aspectos cognitivos y conductuales son un factor muy importante para la adecuada adaptación social, familiar y escolar de estos niños. Objetivo: Describir los perfiles neuropsicológicos de un grupo de niños adoptados internacionalmente en Cataluña procedentes de China, Rusia, Colombia y Etiopía. Pacientes y métodos: Exploración neuropsicológica de 49 niños procedentes de adopción internacional (6 de origen chino, 24 de origen ruso, 13 de origen colombiano y 6 de origen etíope). Resultados: El grupo de origen chino muestra normalidad en todas las funciones evaluadas. El grupo de origen ruso presenta alteración en atención selectiva, fluencia verbal fonética, control de la impulsividad, mecánica y comprensión lectora y ortografía. El grupo de origen colombiano presenta alteración en el control de la impulsividad. El grupo de origen etíope muestra normalidad en todas las funciones evaluadas exceptuando un bajo dominio ortográfico. Conclusión: Los niños adoptados procedentes de Rusia presentan mayores dificultades neuropsicológicas que el resto. La mayoría de antecedentes previos a la adopción se desconocen, por lo que no podemos justificar el origen de estas dificultades. Algunas hipótesis relacionan el consumo materno de alcohol durante la gestación y la estancia en instituciones como posibles factores influyentes. Recomendamos la inclusión de valoraciones neuropsicológicas en los protocolos de salud de estos niños en caso de presentar signos sugestivos de trastorno cognitivo y/o conductual (AU)

Introduction: During the last years, International adoption has increased significantly in our country over the last few years. China, Russia, Colombia and Ethiopia represent 77% of international adoptions in Spain. Cognitive and behavioural aspects are very important for an adequate social, family and school integration of these children. Objective: To describe the neuropsychological profiles of a group of internationally adopted children in Catalonia from China, Russia, Colombia and Ethiopia.Patients and methods: Neuropsychological examination of 49 children from international adoption (6 of Chinese origin, 24 from Russia, 13 from Colombia and 6 of Ethiopian origin). Results: The group of Chinese origin obtained average scores of all functions evaluated. The Russian origin group was below the average for, selective attention, phonetic verbal fluency, control of impulsivity, mechanics and reading comprehension, and spelling. Scores on the impulse controlin the Colombian origin group were below average. The group of Ethiopian origin obtained average scores in all functions evaluated except for spelling difficulties. Conclusion: Children adopted from Russia have greater neuropsychological difficulties than the others. Most pre-adoption history is unknown; therefore we are unable to determine the origin of these difficulties. Maternal alcohol consumption during pregnancy and the institutional environment could be influencing factors in neuropsychological delay. Inclusion of neuropsychological assessment in health protocols for these children is recommended if they develop suggestive signs of cognitive and/or behavioral impairment (AU)

[Neuropsychological profile of internationally adopted children in Catalonia]. / Perfil neuropsicológico de niños adoptados internacionalmente en Cataluña.

INTRODUCTION: During the last years, International adoption has increased significantly in our country over the last few years. China, Russia, Colombia and Ethiopia represent 77% of international adoptions in Spain. Cognitive and behavioural aspects are very important for an adequate social, family and school integration of these children. OBJECTIVE: To describe the neuropsychological profiles of a group of internationally adopted children in Catalonia from China, Russia, Colombia and Ethiopia. PATIENTS AND METHODS: Neuropsychological examination of 49 children from international adoption (6 of Chinese origin, 24 from Russia, 13 from Colombia and 6 of Ethiopian origin). RESULTS: The group of Chinese origin obtained average scores of all functions evaluated. The Russian origin group was below the average for, selective attention, phonetic verbal fluency, control of impulsivity, mechanics and reading comprehension, and spelling. Scores on the impulse control in the Colombian origin group were below average. The group of Ethiopian origin obtained average scores in all functions evaluated except for spelling difficulties. CONCLUSION: Children adopted from Russia have greater neuropsychological difficulties than the others. Most pre-adoption history is unknown; therefore we are unable to determine the origin of these difficulties. Maternal alcohol consumption during pregnancy and the institutional environment could be influencing factors in neuropsychological delay. Inclusion of neuropsychological assessment in health protocols for these children is recommended if they develop suggestive signs of cognitive and/or behavioral impairment.

[Predictive variables for mental retardation in a Pediatric Epilepsy Monitoring Unit. Neuropsychological assessment]. / Variables predictoras de retraso mental en una unidad de monitorización videoelectroencefalográfica pediátrica. Evaluación neuropsicológica.

AIM: We sought to describe the epidemiological and clinical data from our patients in the Pediatric Epilepsy Monitoring Unit (PEMU) of the Sant Joan de Deu Hospital of Barcelona, and determine the variables of risk for mental retardation. PATIENTS AND METHODS: A retrospective review of PEMU reports and hospital discharge summaries from March 2005 to December 2008 was conducted. The data from patients with intelligence quotient (IQ) estimated, older than 3 years of age and with epileptic electroencephalography (EEG) activity was analyzed in 158 patients (8.8 +/- 5.2 years; 55.1% boys). Of those pediatric patients, 63 had IQ less than 70 and 47 an IQ greater than or equal to 70. Intractable epilepsy was present in all of them. RESULTS: The percentage of the patients with mental retardation is significantly higher in patients with onset of epilepsy before 24 months (68.3%) than patients with later onset (27.7%). Onset of seizures, EEG findings and epilepsy etiology are significant risk factors for mental retardation. CONCLUSIONS: Early age at seizure, multifocal epilepsy and cryptogenic etiology are factors of worse prognosis to normal development of cognitive functions in pediatric intractable epilepsy.

Cognitive functions in patients with phenylketonuria in long-term treatment with tetrahydrobiopterin.

Cognitive functions were assessed in 9 patients with mild to moderate phenylketonuria (PKU) ranging from 6 to 18 years of age, who were in long-term treatment (>5 years) with 5-9 mg/kg/day tetrahydrobiopterin (BH4) on compassionate use, provided by Schircks Inc. An extensive study of cognitive functions (intelligence quotient (IQ), visuospatial, visual memory, fine motor, executive and attentional functions) was conducted, and behavior was assessed using the ADHD Rating Scale and the Behavior Rating Inventory of Executive Function (BRIEF). All patients had normal IQ (M=107, SD=10). The most notable area of impairment was fine motor function, but no significant difference was found between the PKU patients in BH4 treatment who participated in the current study and PKU patients in dietary treatment who participated in a previous study. These results, however, should be interpreted with caution. It is necessary to conduct further studies with a larger number of patients, using more sensitive tests of motor function and using the formulation of BH4 that is currently available.

[Neuropsychological aspects of acquired diffuse brain injury in paediatric childhood]. / Aspectos neuropsicológicos del daño cerebral difuso adquirido en la edad pediátrica.

INTRODUCTION AND DEVELOPMENT: Acquired brain injury is one of the most common causes of long-term disability in childhood and traumatisms are the most prevalent cause. Diffuse axonal injury is associated with poor neuropsychological outcome. In contrast to early focal lesions, young age confers no advantage in the outcome of severe diffuse brain injury. Plasticity is incomplete for structural and functional deficits in children. The traditional view of enhanced reorganization of function after localized brain injury it can't be applied in early severe diffuse brain injury. In the paediatric population where the central nervous system is in a rapid state of growth, developmental factors may mask the difficulties and deficits in certain skills may not be evident until that skill is expected to emerge at a certain age. CONCLUSION: Like in adults the neuropsychological domains more affected in childhood are psychomotor speed, memory, attention and executive functioning. In childhood neuropsychological deficits will affect learning and adaptive behaviour. Sometimes deficits will be cumulative over time.

[Non-verbal learning disorder: cognitive-behavioural characteristics and neuropsychological aspects]. / Trastorno de aprendizaje no verbal: características cognitivo-conductuales y aspectos neuropsicológicos.

INTRODUCTION AND DEVELOPMENT: Non verbal learning disorder is a neurological condition which is considered to be a developmental disability. It is characterised by a specific dysfunction in motor, visuospatial and social skills in patients with a normal intellect and development of language. Warning signs in school are poor psychomotor coordination, arithmetic skills and drawing activities. Social judgment and social problem solving are also typically impaired. Furthermore, these patients seem to have increasing risk of emotional disorders. CONCLUSIONS: Current evidence and theories suggest that dysfunction of white matter in the right hemisphere could be the cause. The clinical characteristics and the diagnostic criteria have not fully agreed on. A comprehensive neuropsychological evaluation reveals specific and heterogeneous patterns of difficulties for each child that would make possible to address and accommodate an educational program.

Aspectos neuropsicológicos del daño cerebral difuso adquirido en la edad pediátrica / Neuropsychological aspects of acquired iffuse brain injury in paediatric childhood

Introducción y desarrollo. El daño cerebral adquirido (DCA) es causa de discapacidad en la edad pediátrica. El traumatismo craneoencefálico grave constituye la causa más frecuente de DCA. El pronóstico vital del DCA es más favorable en el niño que en el adulto. No sucede así con el pronóstico neuropsicológico, que es más desfavorable cuanto menor es la edad en el momento de producirse la lesión. En el daño cerebral difuso la plasticidad y capacidad de reorganización cerebral tienen un efecto limitado en la compensación de los déficit cognitivos y conductuales. Debido al proceso de desarrollo del sistema nervioso del niño, la repercusión del DCA puede tardar años en ser evidente. Las demandas crecientes en la escuela, de autonomía y de adaptación social, harán que las dificultades puedan ser progresivas con la edad. Conclusión. Las funciones neuropsicológicas más afectadas, igual que en la edad adulta, son la velocidad psicomotora, memoria, funciones ejecutivas y atencionales. El proceso de desarrollo y aprendizaje del niño hará que la repercusión sea mucho mayor (AU)

Introduction and development. Acquired brain injury is one of the most common causes of long-term disability in childhood and traumatisms are the most prevalent cause. Diffuse axonal injury is associated with poor neuropsychological outcome. In contrast to early focal lesions, young age confers no advantage in the outcome of severe diffuse brain injury. Plasticity is incomplete for structural and functional deficits in children. The traditional view of enhanced reorganization of function after localized brain injury it can’t be applied in early severe diffuse brain injury. In the paediatric population where the central nervous system is in a rapid state of growth, developmental factors may mask the difficulties and deficits in certain skills may not be evident until that skill is expected to emerge at a certain age. Conclusion. Like in adults the neuropsychological domains more affected in childhood are psychomotor speed, memory, attention and executive functioning. Inchildhood neuropsychological deficits will affect learning and adaptive behaviour. Sometimes deficits will be cumulative over time (AU)

Trastorno de aprendizaje no verbal: características cognitivo-conductuales y aspectos neuropsicológicos / Non-Verbal learning disorder: Cognitive behavioural characteristics and neuropsychological aspects

Introducción y desarrollo. El trastorno de aprendizaje no verbal es un trastorno de base neurobiológica que se caracteriza por una disfunción específica en habilidades motrices y visuoespaciales/visuoconstructivas y por dificultades en las relaciones sociales, en pacientes con una inteligencia general y habilidades lingüísticas preservadas. En la escuela, los niños afectados presentan alteraciones en la psicomotricidad y en tareas de dibujo, plástica y cálculo. Con frecuencia se asocian dificultades en la relación social (percepción social, juicio y habilidades de interacción social) y existe una predisposición a padecer problemas emocionales. Conclusiones. Fisiopatológicamente se ha relacionado con una disfunción hemisférica cerebral derecha en la sustancia blanca. Las características clínicas y los criterios diagnósticos no están totalmente definidos. La exploración neuropsicológica pone de manifiesto perfiles clínicos diferentes. Es importante una temprana identificación para poner en marcha las estrategias educativas adecuadas en cada caso (AU)

Introduction and development. Non verbal learning disorder is a neurological condition which is considered to be a developmental disability. It is characterised by a specific dysfunction in motor, visuospatial and social skills in patients with a normal intellect and development of language. Warning signs in school are poor psychomotor coordination, arithmetic skills and drawing activities. Social judgment and social problem solving are also typically impaired. Furthermore, these patients seem to have increasing risk of emotional disorders. Conclusions. Current evidence and theories suggest that dysfunction of white matter in the right hemisphere could be the cause. The clinical characteristics and the diagnostic criteria have not fully agreed on. A comprehensive neuropsychological evaluation reveals specific and heterogeneous patterns of difficulties for each child that would make possible to address and accommodate an educational program (AU)

[Therapeutic monoclonal antibodies: a little history, a lot of engineering, and... some clinical successes]. / Anticorps monoclonaux à usage thérapeutique: un peu d'histoire, beaucoup d'ingénierie, et... quelques succès cliniques.

Thirty years after their discovery by Milstein and Köhler, monoclonal antibodies have now come of age as therapeutics. Nineteen monoclonal antibodies are on the market and/or have got authorization to be used for the treatment of severe diseases. Many technical efforts have been devoted over the last two decades to the generation of second generation mAbs with better affinities, decreased immunogenicity and optimized effector functions. The development of molecular engineering techniques applied to antibody molecules has also made it possible to design bi-specific antibodies and fusion molecules exhibiting different modules with bi-functional activities. The use of proteomics and genomics combined with phage display allows now the rapid selection of antibodies directed against new targets at a high rate. Many efforts are currently focused on the selection of high-responder patients, the optimization of antibody delivery, schemes of infusion, antibody pharmaco-kinetics and bio-distribution, as well as on a better control of the severe side-effects generated by some antibody treatments.