Traumatic brain injury in the new millennium: new population and new management.

INTRODUCTION: Traumatic brain injury (TBI) is one of the leading causes of death and disability globally. We present a study describing epidemiological changes in severe TBI and the impact these changes have had on management and analysing alternatives that may improve outcomes in this new population. MATERIALS AND METHODS: We performed a retrospective, descriptive, cross-sectional analysis of patients presenting severe TBI at our hospital in the period of 1992-1996 and 2009-2013. We analysed demographic data, including age, sex, mortality, aetiology, anticoagulation, treatment, and functional outcome. RESULTS: We reviewed data from 220 patients. In the second cohort, there were 40% fewer patients, mean age was 12 years older, patients were more frequently receiving anticoagulation therapy, and the percentage of interventions was halved. Aetiology varied, with traffic accidents being the main cause in the first group, and accidental falls and being hit by cars in the second group. There were no intergroup differences for mortality or functional outcomes. CONCLUSION: The age of patients admitted due to severe TBI has increased. As a result of this, the main cause of severe TBI in our population is accidental falls in elderly, anticoagulated patients. Despite the low-energy nature of trauma, patients in the second cohort presented a poorer baseline status, and were less frequently eligible for surgery, with no improvement in mortality or functional outcomes.

El traumatismo craneoencefálico severo en el nuevo milenio. Nueva población y nuevo manejo / Traumatic brain injury in the new millennium: A new population and new management

Introducción: El TCE es una de las principales causas de muerte y discapacidad a nivel mundial. Presentamos este estudio con el objetivo de detallar el cambio epidemiológico de la población que sufre TCE severo, su influencia en el tipo de tratamiento ofrecido y analizar alternativas que mejoren los resultados ante el nuevo tipo de población que afrontamos. Material y métodos: Se ha realizado un análisis descriptivo, transversal y retrospectivo de los pacientes que sufrieron TCE severo en nuestro hospital en los periodos 1992-1996 y 2009-2013. Se analizaron datos demográficos como edad, sexo, mortalidad, etiología, anticoagulación, tratamiento realizado y resultados funcionales. Resultados: Se revisaron 220 pacientes. En la segunda cohorte el número de pacientes con TCE severo disminuyó un 40%, eran de media 12 años mayores, más frecuentemente anticoagulados y las intervenciones se redujeron a la mitad. Varió la etiología, predominando en el primer grupo los accidentes de tráfico y en el segundo las caídas casuales y los atropellos. No hubo diferencias en la mortalidad de ambos grupos, y sí en su situación funcional. Conclusión: En este estudio encontramos un envejecimiento de la población que ingresa por TCE severo. Ello hace que, en la actualidad, la principal causa de TCE severo en nuestra población sean las caídas casuales en pacientes anticoagulados mayores. A pesar de ser traumatismos de poca energía, los pacientes presentan peores condiciones basales y son menos candidatos a cirugía, sin que mejoren la mortalidad ni la situación funcional. (AU)

Introduction: Traumatic brain injury (TBI) is one of the leading causes of death and disability globally. We present a study describing epidemiological changes in severe TBI and the impact these changes have had on management and analysing alternatives that may improve outcomes in this new population. Materials and methods: We performed a retrospective, descriptive, cross-sectional analysis of patients presenting severe TBI at our hospital in the period of 1992-1996 and 2009-2013. We analysed demographic data, including age, sex, mortality, aetiology, anticoagulation, treatment, and functional outcome. Results: We reviewed data from 220 patients. In the second cohort, there were 40% fewer patients, mean age was 12 years older, patients were more frequently receiving anticoagulation therapy, and the percentage of interventions was halved. Aetiology varied, with traffic accidents being the main cause in the first group, and accidental falls and being hit by cars in the second group. There were no intergroup differences for mortality or functional outcomes. Conclusion: The age of patients admitted due to severe TBI has increased. As a result of this, the main cause of severe TBI in our population is accidental falls in elderly, anticoagulated patients. Despite the low-energy nature of trauma, patients in the second cohort presented a poorer baseline status, and were less frequently eligible for surgery, with no improvement in mortality or functional outcomes. (AU)

Traumatic brain injury in the new millennium: A new population and new management. / El traumatismo craneoencefálico severo en el nuevo milenio. Nueva población y nuevo manejo.

INTRODUCTION: Traumatic brain injury (TBI) is one of the leading causes of death and disability globally. We present a study describing epidemiological changes in severe TBI and the impact these changes have had on management and analysing alternatives that may improve outcomes in this new population. MATERIALS AND METHODS: We performed a retrospective, descriptive, cross-sectional analysis of patients presenting severe TBI at our hospital in the period of 1992-1996 and 2009-2013. We analysed demographic data, including age, sex, mortality, aetiology, anticoagulation, treatment, and functional outcome. RESULTS: We reviewed data from 220 patients. In the second cohort, there were 40% fewer patients, mean age was 12years older, patients were more frequently receiving anticoagulation therapy, and the percentage of interventions was halved. Aetiology varied, with traffic accidents being the main cause in the first group, and accidental falls and being hit by cars in the second group. There were no intergroup differences for mortality or functional outcomes. CONCLUSION: The age of patients admitted due to severe TBI has increased. As a result of this, the main cause of severe TBI in our population is accidental falls in elderly, anticoagulated patients. Despite the low-energy nature of trauma, patients in the second cohort presented a poorer baseline status, and were less frequently eligible for surgery, with no improvement in mortality or functional outcomes.

Activation of Th lymphocytes alters pattern expression and cellular location of VIP receptors in healthy donors and early arthritis patients.

Vasoactive Intestinal Peptide (VIP) is an important immunomodulator of CD4+ cells in normal and pathological conditions, which exerts its anti-inflammatory and immunomodulatory actions through VPAC receptors, VPAC1 and VPAC2. Only a decrease in the expression of VPAC1 mRNA on Th cells upon activation has been reported. Thus, the deepening in the knowledge of the behavior of these receptors may contribute to the design of new therapies based on their activation and/or blockade. In this study, we describe the expression pattern, cellular location and functional role of VIP receptors during the activation of human Th cells in healthy conditions and in early arthritis (EA). The protein expression pattern of VPAC1 did not change with the activation of Th lymphocytes, whereas VPAC2 was up-regulated. In resting cells, VPAC1 was located on the plasma membrane and nucleus, whereas it only appeared in the nucleus in activated cells. VPAC2 was always found in plasma membrane location. VIP receptors signaled through a PKA-dependent pathway in both conditions, and also by a PKA-independent pathway in activated cells. Both receptors exhibit a potent immunomodulatory capacity by controlling the pathogenic profile and the activation markers of Th cells. These results highlight a novel translational view in inflammatory/autoimmune diseases.

Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons.

Cell cycle reentry followed by neuronal hyperploidy and synaptic failure are two early hallmarks of Alzheimer's disease (AD), however their functional connection remains unexplored. To address this question, we induced cell cycle reentry in cultured cortical neurons by expressing SV40 large T antigen. Cell cycle reentry was followed by hyperploidy in ~70% of cortical neurons, and led to progressive axon initial segment loss and reduced density of dendritic PSD-95 puncta, which correlated with diminished spike generation and reduced spontaneous synaptic activity. This manipulation also resulted in delayed cell death, as previously observed in AD-affected hyperploid neurons. Membrane depolarization by high extracellular potassium maintained PSD-95 puncta density and partially rescued both spontaneous synaptic activity and cell death, while spike generation remained blocked. This suggests that AD-associated hyperploid neurons can be sustained in vivo if integrated in active neuronal circuits whilst promoting synaptic dysfunction. Thus, cell cycle reentry might contribute to cognitive impairment in early stages of AD and neuronal death susceptibility at late stages.

Unusual redox behaviour of the magnetite/hematite core-shell structures processed by the laser floating zone method.

Magnetite (Fe3O4) offers unique physical and chemical properties, being an important material for many industrial applications. Certain limitations on the application conditions are, however, imposed by the redox stability issue. Fine control of the iron oxidation states represents a challenge for materials engineering. The present work explores relevant redox processes in iron oxides, processed under highly non-equilibrium laser floating zone (LFZ) conditions under atmospheres with different oxygen activities. The as-grown fibres showed a structure composed of the Fe3O4 core and the Fe2O3 shell. This study uncovers unexpectedly lower hematite content and shell thickness for the fibres processed under more oxidizing conditions. Combined structural and microstructural studies, supported by the analysis of the existing literature data, strongly suggest that the redox processes during the LFZ process can be rather determined by kinetics of melt crystallization, nuclei formation and heat transfer than by the oxygen content in the gas phase. The proposed mechanisms are further confirmed by electrical and magnetic studies of the composite fibres.

Rubella antibodies in cord blood sera in Portugal: association with maternal age and vaccination status.

This study evaluated the impact of maternal vaccination against rubella on the levels of specific rubella IgG (rIgG) in 198 newborn cord sera samples. Detailed maternal vaccination data were available. Specific rIgG was measured using a commercial enzyme immunoassay. Most mothers (78.8%) had been vaccinated against rubella at least once in their lives. In 15 (7.6%) cord sera samples, the concentration of specific rIgG was below 11 IU/ml, which was classified as seronegative. Statistical analysis using multiple logistic regression (n = 198) showed that newborns of mothers born between 1986 and 1995, and those born to unvaccinated mothers, were more likely to be seronegative (odds ratio (ORs) 5.2 and 4.9, respectively, adjusted for sex and gestational age). For vaccinated mothers (n = 156), those born between 1986 and 1995 were more likely to have seronegative newborns (OR 11.5 adjusting for sex, gestational age and time since last vaccination). Mothers of the 15 (7.6%) seronegative newborns might have been susceptible to rubella during pregnancy. Checking the vaccination status therefore recommended.

Persistence of rubella and mumps antibodies, following changes in the recommended age for the second dose of MMR vaccine in Portugal.

In Portugal, the recommended age for the second dose of MMR (MMR2) was changed from 10-13 years to 5-6 years for those born in 1994 and afterwards. This study aimed to assess if MMR schedule and time elapsed from the last dose are associated with the concentration of rubella and mumps IgG antibodies. Three Portuguese birth cohorts (convenience samples) were selected for this study (66, 59 and 41 participants born respectively in 1990-1993, 1994-1995 and 2001-2003). Geometric mean concentrations (GMC) for mumps IgG were respectively 36, 30 and 38 RU/ml (P = 0·236) and for rubella IgG were 18, 20 and 17 IU/ml (P = 0·641). For both specific antibodies, no differences were observed with time since MMR2. Receiving MMR2 at 5-6 or 10-13 years was not associated with concentration of both antibodies. The GMC of rubella IgG was lower in males (P = 0·029). Taking into account previous evidence and the logistics needed to change vaccination schedules, it seems reasonable that sustaining very high coverage with two doses of MMR is currently the most pragmatic way to control mumps and rubella rather than any changes to the schedule.

Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL.

Prospects and challenges of iron pyroelectrolysis in magnesium aluminosilicate melts near minimum liquidus temperature.

Although steel production by molten oxide electrolysis offers potential economic and environmental advantages over classic extractive metallurgy, its feasibility is far from being convincingly demonstrated, mainly due to inherent experimental difficulties exerted by harsh conditions and lack of knowledge regarding relevant mechanisms and physico-chemical processes in the melts. The present work was intended to demonstrate the concept of pyroelectrolysis at very high temperature near the minimum liquidus point of magnesium aluminosilicate, being conducted under electron-blocking conditions using yttria-stabilized zirconia cells, and to provide a new insight into electrochemistry behind this process. Significant current yields are possible for pyroelectrolysis performed in electron-blocking mode using a solid electrolyte membrane to separate the anode and the molten electrolyte. Parasitic electrochemical processes rise gradually as the concentration of iron oxide dissolved in the molten electrolytes is depleted, impairing faradaic efficiency. Reduction of silica to metallic silicon was identified as a significant contribution to those parasitic currents, among other plausible processes. Direct pyroelectrolysis without electron blocking was found much less plausible, due to major limitations on faradaic efficiency imposed by electronic leakage and insufficient ionic conductivity of the aluminosilicate melt. Ohmic losses may consume an excessive fraction of the applied voltage, thus failing to sustain the Nernst potential required for reduction to metallic iron. The results suggest the need for further optimization of the molten electrolyte composition to promote ionic conductivity and to suppress electronic transport contribution, possibly, by tuning the Al/Si ratio and altering the network-forming/modifying behaviour of the iron cations.

Structural and defect chemistry guidelines for Sr(V,Nb)O3-based SOFC anode materials.

Structural and defect chemistry guidelines were used for Nb-substituted SrVO3-δ materials, designed to meet SOFC anode requirements, with emphasis on redox tolerance, thermochemical compatibility with other SOFC materials, electrical conductivity and adjustable changes in oxygen stoichiometry for their prospective impact on electrocatalytic performance. SrV1-xNbxO3-δ (x = 0-0.30) ceramics were prepared by solid-state synthesis and sintered at 1773 K in a reducing atmosphere. XRD and SEM/EDS showed that under these conditions a single-phase cubic perovskite structure appears up to x ≈ 0.25. Electrical conductivity is metallic-like and nearly p(O2)-independent. Although substitution by niobium decreases the conductivity, which still exceeds 100 S cm(-1) for x ≤ 0.20 at temperatures below 1273 K, it also expands the stability domain of the cubic perovskite phase and suppresses partly high thermochemical expansion characteristic of parent SrVO3-δ. The upper p(O2) limit of phase stability was found to shift from ∼2 × 10(-15) atm for the undoped material to ∼2 × 10(-12) atm for x = 0.30, whereas the average thermal expansion coefficient at 773-1223 K decreased from 22.7 × 10(-6) to 13.3 × 10(-6) K(-1). SrV1-xNbxO3-δ perovskites undergo oxidative decomposition in air, which causes dimensional and microstructural changes. However, sluggish kinetics of oxidation under inert gas conditions results in nearly reversible behavior in relatively short-term redox cycles between reducing and inert atmospheres. Subtle structural changes and a close correlation with point defect chemistry clarify these sluggish changes and provide guidelines to retain the metastability.

Towards a high thermoelectric performance in rare-earth substituted SrTiO3: effects provided by strongly-reducing sintering conditions.

Donor-substituted strontium titanate ceramics demonstrate one of the most promising performances among n-type oxide thermoelectrics. Here we report a marked improvement of the thermoelectric properties in rare-earth substituted titanates Sr0.9R0.1TiO3±Î´ (R = La, Ce, Pr, Nd, Sm, Gd, Dy, Y) to achieve maximal ZT values of as high as 0.42 at 1190 K < T < 1225 K, prepared via a conventional solid state route followed by sintering under strongly reducing conditions (10%H2-90%N2, 1773 K). As a result of complex defect chemistry, both electrical and thermal properties were found to be dependent on the nature of the rare-earth cation and exhibit an apparent correlation with the unit cell size. High power factors of 1350-1550 µW m(-1) K(-2) at 400-550 K were observed for R = Nd, Sm, Pr and Y, being among the largest reported so far for n-type conducting bulk-ceramic SrTiO3-based materials. Attractive ZT values at high temperatures arise primarily from low thermal conductivity, which, in turn, stem from effective phonon scattering in oxygen-deficient perovskite layers formed upon reduction. The results suggest that highly-reducing conditions are essential and should be employed, whenever possible, in other related micro/nanostructural engineering approaches to suppress the thermal conductivity in target titanate-based ceramics.

Enhanced BaZrO3 mechanosynthesis by the use of metastable ZrO2 precursors.

The current work assesses the impact of structural differences between stable and metastable ZrO2 precursors on the mechanochemical preparation of BaZrO3. Monoclinic (m-ZrO2) and tetragonal (t-ZrO2) zirconia polymorphs were prepared without stabilizing additives by slow alkaline precipitation. High-energy milling of the individual ZrO2 precursors induced different partial transformations in each case. The as-synthesized m-ZrO2 powders showed partial conversion to the tetragonal polymorph on mechanical activation, reaching about 10% t-ZrO2 after 420 min accompanied by increases in strain. In contrast, the as synthesized t-ZrO2 powders underwent the inverse transformation to the monoclinic phase, producing about 50% m-ZrO2 after 120 min with the liberation of strain. The t-ZrO2 precursor was shown to exhibit the higher reactivity with barium peroxide, yielding significantly earlier formation of barium zirconate under room-temperature mechanosynthesis. The progress of the mechanochemical formation of BaZrO3 has been discussed with respect to the differing behaviour of the ZrO2 precursors upon mechanical activation and associated thermodynamic perspectives.

New development on materials and techniques used in the heraldic designs of illuminated Manueline foral charters by multi-analytical methods.

In the illuminated foral charters commissioned by D. Manuel I, King of Portugal (1495-1521), heraldry played a prominent role. In this work, royal emblems corresponding to the third heraldic design, applied to the Charter of Couto de Teixedo, are studied by means of EDXRF, SEM-EDS, micro-Raman, micro-FTIR and HPLC-DAD to characterize the materials and techniques used to produce this masterpiece of Portuguese Renaissance. By comparing this data with the results previously obtained in other three charters, this research allows for the first time an accurate insight into the reformed manuscripts production, especially since the illuminated charters under consideration were all investigated on the basis of similar micro-spectroscopic techniques. Inks, metal coatings, pigments, organic dyes, fillers or extenders, and binding media are discussed, and their use enlightened by the politic and legal messages the foral charters had to convey. Parchment analysis allowed us to identify the animal species, and all undertaken processes along its preparation. HPLC-DAD allowed us to differentiate the gums used. CaSO4 was observed in the parchment as a degradation product of CaCO3 used in parchment production in the presence of metal sulfates coming from the ink. Pigments used in the different colors as well as some specific phases for some colors were identified. Silvering and gilding processes, metal caratage and silver oxidation compounds were also objects of the present study.

Implementation of a SPR immunosensor for the simultaneous detection of the 22K and 20K hGH isoforms in human serum samples.

We have implemented a Surface Plasmon Resonance (SPR) immunosensor based on a sandwich assay for the simultaneous detection of the two main hGH isoforms, of 22 kDa (22K) and 20 kDa (20K). An oriented-antibody sensor surface specific for both hormone isoforms was assembled by using the biotin-streptavidin system. The immunosensor functionality was checked for the direct detection of the 22K hGH isoform in buffer, which gave high specificity and reproducibility (intra and inter-assay mean coefficients of variation of 8.23% and 9% respectively). The selective determination of the 22K and 20K hGH isoforms in human serum samples in a single assay was possible by using two specific anti-hGH monoclonal antibodies. The detection limit for both hormone isoforms was 0.9 ng mL(-1) and the mean coefficient of variation was below 7.2%. The excellent reproducibility and sensitivity obtained indicate the high performance of this immunosensor for implementing an anti-doping test.

Food anaphylaxis in antiphospholipid syndrome and thrombosis

Background: We have observed that some cases of food anaphylaxis were followed by severe thrombosis associated to anticardiolip in antibodies. Food anaphylaxis associated with antiphospholipid syndrome has seldom been published. Objective: The aims were: 1) to test anticardiolipin antibodies in an important number of patients with anaphylaxis due to vegetal foods and their relationship with possible thrombosis; and 2) to study seed and fruit hypersensitivity in patients with previous thrombotic events associated with antiphospholipid antibodies (aCL). Methods: We included 30 patients diagnosed of thrombosis associated with a CL, 52 patients who suffered from anaphylaxis due to seeds or fruits, and 120 control patients. Haematological, cardiopulmonary vascular and rheumatologic studies had been performed as needed. In vivo and in vitro allergy tests with a large battery of vegetal allergens were carried out in all the patients. Measurement of IgG a CL antibodies and specific IgE to vegetal food was done by ELISA and CAP-FEIA (Phadia). Immunodetection and inhibitions with lipoproteins belonging to seedswere performed. Results: Seventy-five percent of the patients diagnosed as having antiphospholipid primary syndrome had specific IgE against different proteins from different vegetable allergens, most of them seeds, and clearly against lipoproteins that were also recognised by the patients with food anaphylaxis but not by the control cases. Among the patients with anaphylaxis, 28% had anticardiolipin antibodies and 17.3% thrombosis. Conclusion: Our study suggests that seed lipoproteins which cause severe food anaphylaxis might have a potential role in the antiphospholipid syndrome and related thrombosis (AU)

Technical advance: Surface plasmon resonance-based analysis of CXCL12 binding using immobilized lentiviral particles.

Use of SPR-based biosensors is an established method for measuring molecular interactions. Their application to the study of GPCRs is nonetheless limited to detergent-solubilized receptors that can then be reconstituted into a lipid environment. Using the chemokine receptor CXCR4 and its specific ligand CXCL12, we outline here a highly reproducible biosensor method based on receptor presentation on the surface of lentiviral particles; the approach is simple and does not require the use of antibodies to achieve correct receptor orientation on the sensorchip surface. We measured the kinetic parameters of CXCR4/CXCL12 binding in a single step and in real time and evaluated the effect of GAG presentation of chemokines on this interaction. The data indicate that at low concentrations, soluble heparin modulates CXCR4/CXCL12 interaction and at high concentrations, abrogates binding. These observations suggest that in addition to their known role in modulating local chemokine availability, GAG affect the receptor/ligand interaction, although their influence on affinity parameters is very limited. The method will also be useful for quantifying these biomarkers in biological fluids and for the development of high-throughput screening for their antagonists.