Evolution of cognitive impairment after a traumatic brain injury: is there any improvement after controlling the practice effect? / Evolución de las alteraciones cognitivas tras un traumatismo craneoencefálico: ¿hay mejoría tras controlar el efecto de la práctica?

INTRODUCTION: The importance of knowing the pattern of evolution of cognitive deficits in the first months after a traumatic brain injury (TBI) has encouraged the development of numerous longitudinal studies. However, the results of most of them should be taken with caution due to the lack of adequate control of practice effects that can lead to overestimating the genuine recovery of cognitive processes. AIM: To describe the cognitive changes between the acute and subacute phases of the TBI controlling the effect of the practice. PATIENTS AND METHODS: Twenty-two patients were assessed in two different time points after TBI (immediately and after six months) using the following tests: Trail Making Test (A, B, B/A, B-A), Stroop Test (W, C, CW, interference), Digit Symbol-Coding, Symbol Search, Digits Forward and Backward, Verbal Fluency and Short-term Memory. To control for the practice effects, a transformation of the scores was performed applying the procedure proposed by Calamia et al. RESULTS. Before controlling the practice effects, the scores of all tests improved (p > 0.001). However, afterward, the improvement remained only in the Trail Making Test-B, B/A and B-A, Digit Symbol-Coding, Symbol Search, Stroop CW and Digits Backward. CONCLUSIONS: The lack of control of practice effects in longitudinal studies can generate misleading interpretations about the evolution of cognitive deficits. The pattern of recovery after a TBI varies depending on the cognitive process.

TITLE: Evolución de las alteraciones cognitivas tras un traumatismo craneoencefálico: ¿hay mejoría tras controlar el efecto de la práctica?Introducción. La importancia de conocer el patrón de evolución de los déficits cognitivos en los primeros meses tras un traumatismo craneoencefálico (TCE) ha fomentado el desarrollo de numerosos estudios longitudinales. Sin embargo, los resultados de la mayoría de ellos deberían tomarse con cautela debido a la falta de un control adecuado del efecto de la práctica, que puede llevar a sobreestimar la recuperación genuina de los procesos cognitivos. Objetivo. Describir los cambios cognitivos entre las fases aguda y subaguda del TCE controlando el efecto de la práctica. Pacientes y métodos. Veintidós pacientes realizaron dos evaluaciones neuropsicológicas tras el TCE (inmediata y tras seis meses) mediante los siguientes tests: Trail Making Test (A, B, B/A y B-A), test de Stroop (P, C, PC e interferencia), clave de números, búsqueda de símbolos, dígitos directos e inversos, fluidez verbal y memoria inmediata. Para controlar el efecto de la práctica se realizó una transformación de las puntuaciones aplicando el procedimiento propuesto por Calamia et al. Resultados. Antes de controlar el efecto de la práctica, se evidenció una mejoría en las puntuaciones de todos los tests (p > 0,001). Sin embargo, tras él, la mejoría permaneció sólo en el Trail Making Test-B, B/A y B-A, la clave de números, la búsqueda de símbolos, el test de Stroop PC y los dígitos inversos. Conclusiones. La falta de control del efecto de la práctica en estudios longitudinales puede generar interpretaciones erróneas sobre el perfil de evolución de los déficits cognitivos. El patrón de recuperación tras un TCE varía en función del proceso cognitivo.

MoS2 flakes stabilized with DNA/RNA nucleotides: In vitro cell response.

Two-dimensional transition metal dichalcogenides (TMDCs), such as MoS2 and WS2, have recently emerged as nanomaterials with potential use in biomedicine. An attractive means to favor their interaction with biological media is the use of proper biomolecules as exfoliating/dispersing agents. Here, MoS2 flakes were stabilized with different small functional biomolecules such as adenosine monophosphate (AMP), guanosine monophosphate (GMP) and flavin mononucleotide (FMN) through the strong nucleotide-MoS2 interaction of Lewis acid-base type, rather than just on the weak dispersive and hydrophobic forces commonly associated with the use of many surfactants. The impact of the nucleotide-stabilized MoS2 flakes on the viability and cell proliferation, on the production of intracellular reactive oxygen species (ROS), and on the preosteoblast differentiation process (early stage) has been also evaluated, as well as the incorporation and intracellular localization of the nanomaterials by MC3T3-E1 and Saos-2 cells. The nucleotide-stabilized MoS2 flakes were found to exhibit excellent biocompatibility. Furthermore, their incorporation did not affect the integrity of the cell plasma membrane, which makes them ideal candidates for delivering drug/gene directly into cells. The in vitro cell response of tumor cells to these nanomaterials differs from that of undifferentiated cells, which provides the basis for their potential use in cancer therapy.

Non-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation.

X-linked myotubular myopathy (XLMTM) is a rare neuromuscular condition caused by mutations in the MTM1 gene. Female carriers are believed to be usually asymptomatic; nevertheless, recent reports have displayed a wide a spectrum of clinical involvement in females suggesting that MTM1 mutations might be underestimated in this population. Here we report a 55-year-old woman manifesting with an abrupt respiratory decline, whose respiratory function tests revealed a severe restrictive ventilatory defect. The neurological examination identified mild proximal leg weakness and her cardiac evaluation showed a non-compaction cardiomyopathy with normal left ventricle function. Muscle biopsy was consistent with centronuclear myopathy. Next-generation sequencing of 49 genes related to congenital myopathies allowed the identification of a 4 bp deletion in the MTM1 gene, leading to a truncating mutation previously described in males but for the first time reported in a female patient.

Differential effects of graphene oxide nanosheets on Candida albicans phagocytosis by murine peritoneal macrophages.

Macrophages, as effector cells involved in the innate and adaptive immunity, play a key role in the response to nanomaterials as graphene oxide (GO) and in their cellular uptake. The interactions at the interface of GO nanosheets, macrophages and microbial pathogens need to be assessed to determine the possible impairment of the immune system induced by biomedical treatments with this nanomaterial. Here, we have evaluated by flow cytometry and confocal microscopy the ability of murine peritoneal macrophages to phagocytose the fungal pathogen Candida albicans, alive or heat-killed, after treatment with poly(ethylene glycol-amine)-derivatized GO nanosheets (PEG-GO). After GO treatment, differences in fungal phagocytosis were observed between macrophages that had taken up GO nanosheets (GO+ population) and those that had not (GO- population). GO treatment increased the ingested alive yeasts in GO- macrophages, whereas phagocytosis diminished in the GO+ population. Ingestion of heat-killed yeasts was slightly higher in both GO- and GO+ populations when comparing with control macrophages. For the first time, we show that GO uptake by macrophages modulates its phagocytic capability, affecting differentially the subsequent ingestion of either alive or heat-killed yeasts. Enhanced ingestion of heat-killed yeast by GO-treated macrophages suggests a beneficial role of this nanomaterial for the clearance of dead microorganisms during infection.

Diamond-Graphite Nanoplatelet Surfaces as Conductive Substrates for the Electrical Stimulation of Cell Functions.

The nanocarbon allotropes constitute valid alternatives when designing control and actuation devices for electrically assisted tissue regeneration purposes, gathering among them important characteristics such as chemical inertness, biocompatibility, extreme mechanical properties, and, importantly, low and tailorable electrical resistivity. In this work, coatings of thin (100 nm) vertically aligned nanoplatelets composed of diamond (5 nm) and graphite were produced via a microwave plasma chemical vapor deposition (MPCVD) technique and used as substrates for electrical stimulation of MC3T3-E1 preosteoblasts. Increasing the amount of N2 up to 14.5 vol % during growth lowers the coatings' electrical resistivity by over 1 order of magnitude, triggers the nanoplatelet vertical growth, and leads to the higher crystalline quality of the nanographite phase. When preosteoblasts were cultured on these substrates and subjected to two consecutive daily cycles of 3 µA direct current stimulation, enhanced cell proliferation and metabolism were observed accompanied by high cell viability. Furthermore, in the absence of DC stimulation, alkaline phosphatase (ALP) activity is increased significantly, denoting an up-regulating effect of preosteoblastic maturation intrinsically exerted by the nanoplatelet substrates.

[Atypical ganglioglioma with BRAF V600E mutation: a case report and review of the literature]. / Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.

INTRODUCTION: Gangliogliomas are rare tumours that affect young patients, appear predominantly in the temporal lobe and usually begin with epileptic seizures. Histologically they have a grade I of malignancy, with an anaplastic form that is catalogued as grade III in the 2007 WHO classification. Yet, there are tumours that do not meet the criteria of either grade and which offer clear prognostic differences with respect to those of grade I. These tumours would be atypical gangliogliomas (grade II), which are not considered in this classification. From the molecular point of view, the best known alteration in gangliogliomas is the BRAF V600E mutation, which worsens the prognosis of the lesion. The possible use of treatments targeted towards this mutated protein is especially relevant in this disorder. CASE REPORT: A 21-year-old male, who had undergone surgery due to a ganglioglioma on two occasions. The neuro-pathological examination revealed histological features consistent with an intermediate grade of malignancy (grade II), with positive BRAF mutation. CONCLUSIONS: The case presented here, together with those previously reported in the literature, reopens the debate on the definition of gangliogliomas in the 2007 WHO classification, and lends support to the fact that the next classification should again include atypical gangliogliomas (grade II), together with possible genetic mutations and molecular disorders.

TITLE: Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.Introduccion. Los gangliogliomas son tumores raros que afectan a pacientes jovenes, aparecen predominantemente en el lobulo temporal y suelen comenzar con crisis epilepticas. Histologicamente corresponden a un grado I de malignidad, con una forma anaplasica catalogada como de grado III en la clasificacion de la Organizacion Mundial de la Salud (OMS) de 2007. Sin embargo, existen tumores que no cumplen criterios de uno u otro grado y que presentan claras diferencias pronosticas respecto a los de grado I. Estos tumores corresponderian a gangliogliomas atipicos (grado II), no contemplados en la citada clasificacion. Desde el punto de vista molecular, la alteracion mas conocida en los gangliogliomas es la mutacion de BRAF V600E, que confiere peor pronostico a la lesion. La posibilidad de utilizar tratamientos dirigidos a esta proteina mutada otorga una especial relevancia a esta alteracion. Caso clinico. Varon de 21 años, intervenido de un ganglioglioma en dos ocasiones, en el que el examen neuropatologico objetivo caracteristicas histologicas compatibles con un grado de malignidad intermedio (grado II) con mutacion positiva a BRAF. Conclusiones. El caso presentado, junto con los descritos previamente en la bibliografia, reabre las controversias sobre la definicion de los gangliogliomas en la clasificacion de la OMS de 2007, y apoya el hecho de que la proxima clasificacion de la OMS deberia volver a incluir los gangliogliomas atipicos (grado II) e integrar posibles mutaciones geneticas y alteraciones moleculares.

Electrical stimuli to increase cell proliferation on carbon nanotubes/mesoporous silica composites for drug delivery.

The development of smart materials as bone implants is nowadays a challenging task to optimize their fast osteointegration. Nevertheless, no attempts have been done in joining the possibility of using electrical stimulation and drug delivery together in a material intended for bone tissue engineering. Moreover, the use of this synergy to induce bone healing is still limited until novel drug reservoirs material formulations allow an efficient applicability of the electrical stimuli. Herein, we present the biological response of osteoblasts cells, cultured over carbon nanotubes-mesoporous silica composites while exposed to external electrical stimulus. Moreover, its ability to function as drug delivery systems is also demonstrated. Bone cell metabolism was stimulated and mitochondrial activity was increased up to seven times in the presence of these composites under electrical stimulus, suggesting their potential application in bone regeneration processes.

Severe traumatic head injury: prognostic value of brain stem injuries detected at MRI.

BACKGROUND AND PURPOSE: Traumatic brain injuries represent an important cause of death for young people. The main objectives of this work are to correlate brain stem injuries detected at MR imaging with outcome at 6 months in patients with severe TBI, and to determine which MR imaging findings could be related to a worse prognosis. MATERIALS AND METHODS: One hundred and eight patients with severe TBI were studied by MR imaging in the first 30 days after trauma. Brain stem injury was categorized as anterior or posterior, hemorrhagic or nonhemorrhagic, and unilateral or bilateral. Outcome measures were GOSE and Barthel Index 6 months postinjury. The relationship between MR imaging findings of brain stem injuries, outcome, and disability was explored by univariate analysis. Prognostic capability of MR imaging findings was also explored by calculation of sensitivity, specificity, and area under the ROC curve for poor and good outcome. RESULTS: Brain stem lesions were detected in 51 patients, of whom 66% showed a poor outcome, as expressed by the GOSE scale. Bilateral involvement was strongly associated with poor outcome (P < .05). Posterior location showed the best discriminatory capability in terms of outcome (OR 6.8, P < .05) and disability (OR 4.8, P < .01). The addition of nonhemorrhagic and anterior lesions or unilateral injuries showed the highest odds and best discriminatory capacity for good outcome. CONCLUSIONS: The prognosis worsens in direct relationship to the extent of traumatic injury. Posterior and bilateral brain stem injuries detected at MR imaging are poor prognostic signs. Nonhemorrhagic injuries showed the highest positive predictive value for good outcome.

Novel biopolymer-coated hydroxyapatite foams for removing heavy-metals from polluted water.

3D-macroporous biopolymer-coated hydroxyapatite (HA) foams have been developed as potential devices for the treatment of lead, cadmium and copper contamination of consumable waters. These foams have exhibited a fast and effective ion metal immobilization into the HA structure after an in vitro treatment mimicking a serious water contamination case. To improve HA foam stability at contaminated aqueous solutions pH, as well as its handling and shape integrity the 3D-macroporous foams have been coated with biopolymers polycaprolactone (PCL) and gelatine cross-linked with glutaraldehyde (G/Glu). Metal ion immobilization tests have shown higher and fast heavy metals captured as function of hydrophilicity rate of biopolymer used. After an in vitro treatment, foam morphology integrity is guaranteed and the uptake of heavy metal ions rises up to 405 µmol/g in the case of Pb(2+), 378 µmol/g of Cu(2+) and 316 µmol/g of Cd(2+). These novel materials promise a feasible advance in development of new, easy to handle and low cost water purifying methods.