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Gangliogliomas are well-differentiated, slow-growing tumors. The majority are gradeI of WHO. It appears predominantly in children and young adults. Most are located at the temporal lobe, and as symptomatology more frequent epileptic seizures of difficult pharmacological control. In general, they have a good prognosis after surgical resection. The anaplasic variant, considered to be gradeIII of the WHO, presents greater clinical and radiological aggressiveness. Leptomeningeal dissemination is exceptional in these types of tumors, but when diagnosed it presents a rapidly progressive and fatal course for the patient.

Background: Treatment optimization for serious infections, such as Staphylococcus aureus bacteremia (SAB), is a challenge for antimicrobial stewardship teams. Currently, SAB guidelines recommend a completely intravenous therapy (CIT). Objectives: The objective of the study was to analyze the usefulness and safety of oral sequential therapy (OST) in SAB. Patients and methods: We conducted a retrospective, observational study in a tertiary teaching hospital in Spain. The inclusion criteria were complicated and non-complicated monomicrobial SAB and an adequate duration of therapy, with patients classified into OST or CIT. The primary endpoint was the 90-day recurrence of S. aureus infection. We also analyzed the mortality, the length of the hospital stay, and the duration of the intravenous antibiotic administration. Results: Of a total of 201 patients with SAB, 125 (62%) underwent OST. The most commonly administered oral antibiotic was trimethoprim-sulfamethoxazole (66% of patients). Of those administered OST, 43% had complicated bacteremia (most with an osteoarticular source of infection), and 6% had an intravascular device. The 90-day recurrence rate was 4%, with no differences between the two groups. The duration of the therapy (22 [16–28] vs. 13 days [8–17] for CIT and OST, respectively; p < 0.001) and the hospital stay (36 [27–71] vs. 18 days [13–29] for CIT and OST, respectively; p < 0.001) were shorter for OST. MRSA was related with mortality (OR 4.4, 95% CI [1.67−11.37]; p = 0.003). Conclusions: OST for properly selected patients with SAB could be a safe therapeutic option and can reduce their use of CIT and their hospital stay.

Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, an important respiratory disease for the pig industry. A. pleuropneumoniae has traditionally been considered an obligate pig pathogen. However, its presence in the environment is starting to be known. Here, we report the A. pleuropneumoniae surviving in biofilms in samples of drinking water of swine farms from Mexico. Fourteen farms were studied. Twenty drinking water samples were positive to A. pleuropneumoniae distributed on three different farms. The bacteria in the drinking water samples showed the ability to form biofilms in vitro. Likewise, A. pleuropneumoniae biofilm formation in situ was observed on farm drinkers, where the biofilm formation was in the presence of other bacteria such as Escherichia coli, Stenotrophomonas maltophilia, and Acinetobacter schindleri. Our data suggest that A. pleuropneumoniae can inhabit aquatic environments using multi-species biofilms as a strategy to survive outside of their host.

Livestock are known reservoirs of methicillin-resistant Staphylococcus aureus (MRSA) and this constitutes an important public health issue. The prevalence of nasal MRSA carriers in swine housed indoors in Galicia, Spain, was studied.197 samples from swine aged three, eight, 12, 16 and 24 weeks, and from adult pigs, were obtained from four farms. The cleaning procedures implemented to clean the barns and antimicrobial consumption were analyzed. Antimicrobial susceptibility and antimicrobial resistance genes were studied. PFGE, spa typing and MLST were used to classify the isolates. SCCmec, agr and pvl were analyzed.MRSA prevalence was 12.7%. Swine younger than 16 weeks had a higher colonization rate; 22.9% vs 3.5% (OR, 8.16; 95% CI, 2.47-29.79; p0.01). The only farm found to be MRSA-free used disinfectants as part of its cleaning procedure. All MRSA were tetracycline-resistant (identifying the tetK and tetM genes), 80% were resistant to erythromycin and clindamycin and 16% were only clindamycin-resistant. The ermC and vgaA genes were identified in these two phenotypes. A single genotype (PFGE type A) and ST398 - spa t011 (84%) and t1451 (16%) were identified. SCCmec type V and agrI were identified in all isolates, and all were pvl-negative.A correlation between swine age and MRSA colonization was observed. Appropriate cleaning procedures could have an impact on MRSA colonization in farming. Resistance to antibiotics used in human health was identified. Clinicians should be aware if their patients have come into contact with farm animals.

Background Ankylosing spondylitis (AS) is associated with high rates of severe thoracolumbar fractures, in many cases with neurological deficits. It is currently a point of debate as to whether the optimal surgical treatment is posterior fixation and fusion or combined approaches. Vascular injuries in this kind of fracture are a challenging issue to solve in the management of these patients. Methods We are reporting the case of a 65-year-old man who presented an L4 traumatic fracture-dislocation. He had a long history of symptomatic AS. No neurological deficits were detected during the initial exploration. During the preoperative work-up, a lumbar spine computed tomography (CT) scan was taken with vascular reconstruction of the abdominal vessels. It confirmed the compression of the abdominal aorta, which had caused more than 90% stenosis. A posterior approach, an open reduction, and fixation with pedicle screws were performed, without hemodynamic or neurological changes. A postoperative angiography demonstrated a complete recovery of the vessel caliber, without contrast leaks. Results After a 2-year follow-up, the patient was pain free and the CT scan revealed bone fusion. Conclusions The vascular structures involved in severe thoracolumbar fractures present a dangerous situation that should be considered in the choice of the surgical approach. The posterior approach alone may be a good option in the absence of vascular damage. However, due to risk of vessel rupture during the fracture reduction, vascular surgeons must take part in the surgery. Level of Evidence 5. Clinical Relevance The article provides help for surgeons who have to treat severe fractures in the context of ankylosing spondylitis

Actinobacillus pleuropneumonia is a swine (host) specific respiratory pathogen and the etiological agent of swine pleuropneumonia which affects pigs of all ages, many being asymptomatic carriers. This pathogen has high morbidity and mortality rates which generates large economic losses for the pig industry. Actinobacillus pleuropneumoniae is a widely studied bacterium, however its pathogenesis is not yet fully understood. The prevalence of the 18 serotypes of A. pleuropneumoniae varies by geographic region, in North American area, more specifically in Mexico, serotypes 1, 3, 5b, and 7 show higher prevalence. Actinobacillus pleuropneumoniae is described as a strict extracellular pathogen with tropism for lower respiratory tract. However, this study depicts the ability of these serotypes to adhere to non-phagocytic cells, using an endothelial cell model, as well as their ability to internalize them, proposing it could be considered as an intracellular pathogen.

Background Uropathogenic Escherichia coli (UPEC) are one of the main bacteria causing urinary tract infections (UTIs). The rates of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically in recent years and could difficult the treatment. Methods The aim of the study was to determine multidrug-resistant bacteria, antibiotic resistance profile, virulence traits, and genetic background of 110 E. coli isolated from community (79 isolates) and hospital-acquired (31 isolates) urinary tract infections. The plasmid-mediated quinolone resistance genes presence was also investigated. A subset of 18 isolates with a quinolone-resistance phenotype was examined for common virulence genes encoded in diarrheagenic and extra-intestinal pathogenic E. coli by a specific E. coli microarray. Results Female children were the group most affected by UTIs, which were mainly community-acquired. Resistance to trimethoprim–sulfamethoxazole, ampicillin, and ampicillin–sulbactam was most prevalent. A frequent occurrence of resistance toward ciprofloxacin (47.3%), levofloxacin (43.6%) and cephalosporins (27.6%) was observed. In addition, 63% of the strains were multidrug-resistant (MDR). Almost all the fluoroquinolone (FQ)-resistant strains showed MDR-phenotype. Isolates from male patients were associated to FQ-resistant and MDR-phenotype. Moreover, hospital-acquired infections were correlated to third generation cephalosporin and nitrofurantoin resistance and the presence of kpsMTII gene. Overall, fimH (71.8%) and fyuA (68.2%), had the highest prevalence as virulence genes among isolates. However, the profile of virulence genes displayed a great diversity, which included the presence of genes related to diarrheagenic E. coli. Out of 110 isolates, 25 isolates (22.7%) were positive to qnrA, 23 (20.9%) to qnrB, 7 (6.4%) to qnrS1, 7 (6.4%) to aac(6′)lb-cr, 5 (4.5%) to qnrD, and 1 (0.9%) to qnrC genes. A total of 12.7% of the isolates harbored bla CTX-M genes, with bla CTX-M-15 being the most prevalent. Conclusions Urinary tract infection due to E. coli may be difficult to treat empirically due to high resistance to commonly used antibiotics. Continuous surveillance of multidrug resistant organisms and patterns of drug resistance are needed in order to prevent treatment failure and reduce selective pressure. These findings may help choosing more suitable treatments of UTI patients in this region of Mexico.

Resumen Objetivos Descripcion de una complicacion posquirurgica infrecuente, la evisceracion intestinal vaginal, y revision de los factores predisponentes, diagnostico y su tratamiento quirurgico corrector definitivo, las vias de abordaje y las posibles tecnicas quirurgicas, basandonos en la literatura cientifica disponible. Material y metodos Se presenta el caso clinico de una paciente de 46 anos con la complicacion referida, su evaluacion inicial, manejo quirurgico y seguimiento. Se realiza laparotomia para evaluacion de la viabilidad de las asas intestinales herniadas, reparacion del defecto existente en la cupula vaginal y tecnica quirurgica correctora en el mismo tiempo quirurgico, la colposacropexia con malla con buen resultado a corto y medio plazo. Conclusiones La evisceracion vaginal en una complicacion infrecuente que requiere una valoracion rapida y una actitud quirurgica urgente, debido a la alta morbimortalidad a la que se asocia.

Olfactory ensheathing glia (OEG) cells are localized all the way from the olfactory mucosa to and into the olfactory nerve layer (ONL) of the olfactory bulb. Throughout adult life, they are key for axonal growing of newly generated olfactory neurons, from the lamina propria to the ONL. Due to their pro-regenerative properties, these cells have been used to foster axonal regeneration in spinal cord or optic nerve injury models. We present an in vitro model to assay and measure OEG neuroregenerative capacity after neural injury. In this model, reversibly immortalized human OEG (ihOEG) is cultured as a monolayer, retinas are extracted from adult rats and retinal ganglion neurons (RGN) are cocultured onto the OEG monolayer. After 96 h, axonal and somatodendritic markers in RGNs are analyzed by immunofluorescence and the number of RGNs with axon and the mean axonal length/neuron are quantified. This protocol has the advantage over other in vitro assays that rely on embryonic or postnatal neurons, that it evaluates OEG neuroregenerative properties in adult tissue. Also, it is not only useful for assessing the neuroregenerative potential of ihOEG but can be extended to different sources of OEG or other glial cells.

Olfactory ensheathing cells (OECs) are a type of glia from the mammalian olfactory system, with neuroprotective and regenerative properties. β-Amyloid peptides are a major component of the senile plaques characteristic of the Alzheimer brain. The amyloid beta (Aβ) precursor protein is cleaved to amyloid peptides, and Aβ25-35 is regarded to be the functional domain of Aβ, responsible for its neurotoxic properties. It has been reported that Aβ25-35 triggers reactive oxygen species (ROS)-mediated oxidative damage, altering the structure and function of mitochondria, leading to the activation of the mitochondrial intrinsic apoptotic pathway. Our goal is to investigate the effects of OECs on the toxicity of aggregated Aβ25-35, in human neuroblastoma SH-SY5Y cells. For such purpose, SH-SY5Y cells were incubated with Aβ25-35 and OEC-conditioned medium (OECCM). OECCM promoted the cell viability and reduced the apoptosis, and decreased the intracellular ROS and the lipid peroxidation. In the presence of OECCM, mRNA and protein levels of antioxidant enzymes (SOD1 and SOD2) were upregulated. Concomitantly, OECCM decreased mRNA and the protein expression levels of cytochrome c, caspase-9, caspase-3, and Bax in SH-SY5Y cells, and increased mRNA and the protein expression level of Bcl-2. However, OECCM did not alter intracellular Ca2+ concentration in SH-SY5Y cells. Taken together, our data suggest that OECCM ameliorates Aβ25-35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial intrinsic pathway. These data provide new insights into the functional actions of OECCM on oxidative stress-induced cell damage.

Transfontanellar ultrasound is widely used to study neonatal neuroanatomy and disease. This technique has many advantages, such as the absence of ionizing radiation and its wide availability, portability, and low cost. The development of more powerful ultrasound scanners and improved microcurved and linear probes of different frequencies have resulted in improved image quality. To take full advantage of this technique, it is important to know the normal and pathologic anatomy in neonates. Transfontanellar ultrasound is the first-line technique for studying short-term and mid-term complications in premature newborns. In full-term newborns, it is very useful in many clinical situations, making it possible to select which patients will benefit from other techniques that are more invasive or more expensive, or that require sedation, such as MRI. The disadvantages of the technique are that it is operator dependent and that an appropriate acoustic window is necessary. It also has limitations in the study of obstetric trauma, in the evaluation of complex malformations, and in the assessment of damage to white matter. With a basic understanding of neonatal neurology, the appropriate equipment, and a careful technique taking advantage of the different fontanels, transfontanellar ultrasound is a reliable method that makes it possible to diagnose and follow up both congenital and acquired conditions in neonates.

Study design A retrospective study. Purpose We report our experience with 5-aminolevulinic acid (5-ALA)-assisted resection of spinal cord ependymomas in adults. Overview of literature Ependymoma is the most frequent primary spinal cord tumor in adults. Surgery is the treatment of choice in most cases. However, while complete resection is achieved in approximately 80% of cases, clinical improvement is achieved in 15% only. Five-ALA fluorescence-guided surgery seems to be useful for this tumor type. Methods We studied 14 patients undergoing 5-ALA fluorescence-guided surgery for spinal cord ependymomas in our service. The modified McCormick classification was used to determine clinical status and the degree of resection was assessed with magnetic resonance imaging. Results Of the 14 patients, the tumor showed an intense emission of fluorescence in 12 and the fluorescence was weak and nonuniform in two. Complete resection was achieved in 11 cases. According to the McCormick classification, 10 patients improved, two remained the same, and two deteriorated. Conclusions Our results confirm that 5-ALA fluorescence-guided resection is useful in spinal cord ependymoma resection. Although the rate of complete resections is similar to that in published series without 5-ALA, clinical results are better when using 5-ALA with a lower percentage of clinical deterioration.

This is the peer reviewed version of the following article: Gómez RM, Sánchez MY, Portela-Lomba M, et al. Cell therapy for spinal cord injury with olfactoryensheathing glia cells (OECs). Glia. 2018;00:1–35 which has been published in final form at GLIA 13 January (2018) http://doi.org/10.1002/glia.23282. © 2018 Wiley Periodicals This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving., The prospects of achieving regeneration in the central nervous system (CNS) have changed, asmost recent findings indicate that several species, including humans, can produce neurons in adult-hood. Studies targeting this property may be considered as potential therapeutic strategies torespond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma mayinterrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, asseen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs aredue to the immediate and significant disruption of the ascending and descending spinal pathways,which result in varying degrees of motor and sensory impairment. Recent therapeutic studies forSCI have focused on cell transplantation in animal models, using cells capable of inducing axonregeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactoryensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell-based ther-apeutic strategies, there is still little information regarding the mechanisms underlying the successof transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable toachieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulateangiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion.Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both fromanimal models and clinical studies performed on SCI patients, providing promising results for future treatments.

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion., Spanish Ministry of Science and Innovation (BFU2012-32617), the Generalitat de Catalunya (SGR2014-1218), La Caixa Obra Social Foundation, and the Basque Foundation of Health and Innovation Research (BIO12/AL/004) to JADR. RG was supported by Fondo de Investigaciones Sanitarias (PI11-00075) and work in FW’s lab was supported by grants from the Dirección General de Ciencia y Tecnologia-DGCYT-(SAF2012-39148-C03-01), and EU-FP7-2009-(CT222887), as well as an institutional grant from the ‘Fundación Areces

Resumen Objetivo Determinar la seguridad de la traqueotomia percutanea por dilatacion (TPD) en los pacientes receptores de un trasplante hepatico. Pacientes y metodo Se revisaron las historias de los pacientes ingresados para control postoperatorio de trasplante hepatico (n = 291) entre octubre de 2007 y abril de 2013. En este periodo 25 pacientes trasplantados hepaticos requirieron la realizacion de una TPD. Se analizaron entre otros: indices de gravedad (APACHE II y SAPS II), numero de dias desde la intubacion, razon PO 2 /FiO 2 , estudios de coagulacion y complicaciones. Se compararon los resultados con la poblacion general de pacientes criticos y las publicaciones similares en la literatura. Resultados La mediana de edad fue 58 anos (RIC 47-65) y el 64% de los pacientes eran varones. La mediana desde la intubacion hasta la TPD fue 11 dias (RIC 6,5-15,5) y desde el trasplante hasta la TPD, 12 dias. La mediana de la PO 2 /FiO 2 fue de 212 (RIC 177-259). El recuento de plaquetas mostro valores menores en los pacientes trasplantados 89 (RIC 37-149) vs. 272 (RIC 186-381), p = 0,001. Las complicaciones incluyeron: sangrado clinicamente significativo, 8 frente al 0,3% de los pacientes criticos no trasplantados (p = 0,005), infeccion del estoma en el 4% y neumonia asociada a ventilacion mecanica en el 16% (frente al 2,8% del resto de pacientes criticos, p = 0,007). No hubo muertes relacionadas con el procedimiento. Conclusiones La TPD es bien tolerada en los pacientes ingresados en UCI para el control postoperatorio de trasplante hepatico y presenta una tasa relativamente baja de complicaciones graves y mortalidad relacionada con el procedimiento.

Background and objective Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T > G. Patients and methods Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. Results 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. Conclusion We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T > G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time.

These guidelines of the Difficult Airway Society describe a comprehensive strategy to optimize airway management and tracheal intubation in critically ill patients, in all hospital locations., Se trata de una guía de práctica clínica de la Difficult Airway Society (DAS) británica que expone una estrategia para optimizar el manejo de la VA durante la intubación orotraqueal en el paciente crítico adulto, en cualquier localización hospitalaria.

Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) has increased in recent years. The objective of this study was to characterise two MRSA populations, one susceptible to fluoroquinolones and other resistant identifying the clonal types and the differential characteristics of both MRSA populations.Molecular typing using PFGE, MLST, spa and SSCmec was performed on 192 MRSA strains isolated from 2009 to 2011, 49 only oxacillin-resistant (OX-R) and 143 oxacillin and levofloxacin-resistant (OX-R-LEV-R). Mutations that conferred resistance to fluoroquinolones, hypermutable phenotypes and the presence of eight microbial surface components recognising adhesive matrix molecules (MSCRAMMs) were also studied.A statistically significant increase in the OX-R-LEV-R phenotype was observed (p0.05). The most common clone of the OX-R isolates was sequence type (ST) 8 (32.6%), followed by ST72 (26.5%) and ST5 (26.5%). In the OX-R-LEV-R phenotype, the ST5 clone was the most common (65.7%), followed by ST72 (15.4%), and ST125 (12.6%). All isolates except the ST398 clone carried the SCCmecIVc. Clones ST5, ST72, ST125, and ST30 had hypermutable phenotypes. The ST72 clone and the ST30 clone in the OX-R phenotype harboured the highest number of MSCRAMMs.ST5 and ST72 clones were the most frequent clones identified in OX-R-LEV-R phenotype. Both clones showed a hypermutable phenotype that favours their selection as the fluoroquinolone resistant clones. The genetic relationships identified indicate that OX-R-LEV-R clones have evolved from OX-R MRSA clones.

On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.

SummaryVenous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0% were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5%). The diagnosis was deep-vein thrombosis (DVT) in 59.5% and pulmonary embolism (PE) in 40.5%. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5%), hypertension (42.3%) and dyslipidaemia (21.1%). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2%), almost half received a vitamin K antagonist (48.7%) and nearly a quarter received a DOAC (24.5%). Almost a quarter of all presentations were for recurrent VTE, with >80% of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes.

Adherent giant vesicles composed of phosphatidylcholine, phosphatidylserine and biotinylated lipids form clusters of inward spherical buds at their basal membrane. The process is spontaneous and occurs when the vesicles undergo a sequence of osmotic swelling and deswelling. The daughter vesicles have a uniform size (diameter ≈ 2-3 μm), engulf small volumes of outer fluid and remain attached to the region of the membrane from which they generate, even after restoring the isotonicity. A pinning-sealing mechanism of long-wavelength modes of membrane fluctuations is proposed, by which the just-deflated vesicles reduce the surplus of membrane area and avoid excessive spreading and compression via biotin anchors. The work discusses the rationale behind the mechanism that furnishes GUVs with basal endovesicles, and its prospective use to simulate cellular events or to create molecular carriers.

Immortalized cell lines of olfactory ensheathing glia (OEG) that maintain the proregenerative properties of primary cultures provide an unlimited source of OEG for both basic and applied studies. Indeed, one specific immortalized rat OEG clonal line (TEG3) proved to be as good as primary OEG in promoting neuritogenesis and axon regeneration in culture models. Thus, we examined the capacity of TEG3 to promote axonal repair in an animal model of spinal cord injury, dorsal column crush. TEG3 cells can acquire astrocyte-like or Schwann cell-like morphology depending on the conditions under which they are cultured. In the injured spinal cord, prelabeled TEG3 survived for at least 10 weeks after grafting and they integrated into the spinal cord, adopting Schwann cell-like, astrocyte-like, or intermediate morphologies. In TEG3-transplanted animals, sensory projection axons grow into the lesion site and there was robust sprouting/axonal growth of the corticospinal tract, both into and beyond the lesion site, after crushing of the spinal cord–dorsal columns. TEG3-transplanted animals also recovered sensory and motor function in tape removal and beam walking behavioral tests. These data indicate that certain immortalized cell lines derived from a single cell can maintain the regenerative properties of primary OEG., This work was supported by grants from Neuropharma, DGCYT, the Wellcome Trust, and the MRC and by an institutional grant from the Fundación Ramón Areces. M.T.M. was supported by contracts from the Spanish CSIC, Neuropharma, and the Fundación “Severo Ochoa” and was the recipient of an EMBO short-term fellowship. M.J.M. was supported by Neuropharma, M.A. by the BBSRC, and E.P. by an FPI fellowship of the Spanish Ministry.

Semaphorins (sema) constitute a family of molecules sharing a common extracellular domain (semaphorin domain). This family includes several types of secreted and membrane-associated molecules that are grouped into eight subclasses (subclasses 1-7 and viral semaphorins). Subclass 3 semaphorins are secreted molecules involved in axonal guidance, mainly through repulsive gradients and induction of growth cone collapse. More recently sema 3 molecules have been identified as positive factors in dependence of the type of neurons. Besides their axonal guidance function, some semaphorins have been implicated in apoptosis and survival. We investigated the effect of sema3C on survival and neurite outgrowth of rat cerebellar granule neurons (CGNs) in culture. 3T3 cells were stably transfected with sema3C. Several clonal lines were established and tested for their neuritogenic activity and one, S3C-8, was selected for the bulk of experiments. S3C-8 was co-cultured with CGNs. Sema3C enhanced CGN viability as assessed in co-cultures of CGNs with monolayers of S3C-8 in comparison with co-cultures of CGNs with control mock-transfected 3T3 cells. Moreover sema3C induced neuritogenesis of cultured CGNs, which express neuropilin-1 and -2. S3C-8 cells, overexpressing sema3C, were significantly more neuritogenic for CGN than poly l-lysine (PLL), a positive substrate for CGNs, as assessed by the measurement of the length of neurites and confirmed by Tau expression along the time of culture. CGNs co-cultured with S3C-8, showed up-regulation of the expression of axonal microtubule-associated proteins (MAPs) such as Tau, phosphorylated MAP2C and mode I-phosphorylated MAP1B compared with neurons cultured on control 3T3 cells. We also found increased expression of a specific marker of neuronal cell bodies and dendrites, high molecular weight MAP2 (HMW-MAP2). Interestingly, there was no accompanying up-regulation of a marker enriched within the neuronal somatodendritic domain, mode II-phosphorylated MAP1B. These data support the idea that secreted sema3C favors survival and neuritogenesis of cultured CGNs.

Olfactory bulb ensheathing glia (OEG) have attracted special attention during the last few years because of their unique properties in promoting regeneration of adult mammalian central nervous system (CNS) components. However the molecular and cellular characteristics responsible for this capacity remain to be revealed. Such studies are presently hindered by the lack of a plentiful source of homogenous OEG. Thus the availability of immortalized OEG lines maintaining the regenerative characteristics of the primary cultures would represent an unlimited source of OEG for use not only in biochemical analyses of neuroregenerative mechanisms but also to characterize their regenerative properties in models in culture and in vivo. We have immortalized primary rat OEG using the SV40 large T antigen expressed from a constitutive cellular promotor, and report here the isolation and characterization of clonal lines. These OEG clonal lines were comparable to primary OEG and Schwann cells in the promotion of axonal regeneration of mature rat retinal ganglion neurons (RGN) but, significantly, this culture assay system more closely reflects the in vivo reparative properties of OEG on transected nerves than other assays of neuritogenesis in that it revealed OEG cells to promote the growth of a larger number of long axons than Schwann cells. Using this assay we were able to grade our OEG lines for their neuroregenerative capacity, opening the possibility of identifying molecules with correlative expression levels in these cells. Our preliminary characterization revealed that the expression level of a classical OEG marker, the p75-NGF receptor, does not correlate with neuroregenerative capacity.

Varon de 52 anos, cazador, que acudio a urgencias por dolor abdominal de 24 h de evolucion, febricula y nauseas. La exploracion abdominal mostraba dolor y defensa en fosa iliaca derecha. La radiografia anteroposterior de abdomen (fig. 1) revelo la presencia de mu ltiples imagenes radiopacas redondeadas de pequeno tamano y distribucion en cadena, localizadas en flanco-fosa iliaca derecha. El paciente fue intervenido de forma urgente mediante incision de McBurney, hallandose un apendice ileocecal con paredes engrosadas, con cuerpos extranos en su interior. Se realizo apendicectomia. La anatomia patologica confirmo el diagnostico de apendicitis aguda con presencia de mu ltiples perdigones en la luz apendicular (fig. 2). c i r e s p . 2 0 1 5 ; 9 3 ( 8 ) : 5 3 6

During all the life of a mammal, olfactory ensheathing glia (OEG) permit the entry and navigation of olfactory neuron axons from peripheral to central nervous system (CNS) territory. This physiological characteristic of OEG has been successfully used for promotion of axonal regeneration after CNS injury in animal models. However, cellular and molecular properties responsible for OEG regenerative ability remain to be unveiled. Two approaches may be followed: to carry out genomic or proteomic analysis to detect secreted and/or membrane bound molecules or to examine the expression of molecules previously described as neuritogenic. This is the case of amyloid precursor protein (APP), a neurite-promoting molecule. We have studied the expression of APP by OEG and OEG-derived clonal lines, immortalised with the large T antigen of SV40 (TEG lines). OEG express high levels of APP in vivo and in culture. TEG lines maintained high expression of APP. Western blot analysis showed the presence of high molecular weight forms of APP in OEG, corresponding probably to glycosylated forms and/or to higher expression of the full length APPs. The main APP isoforms present in OEG cultures were APP770 and 751. L-APP isoforms without the exon 15, which are those corresponding with proteoglycan forms, are predominant in glial cells. Our data showed that OEG had three times as much L-APP as astrocytes, which may correlate with OEG neuritogenic capacity. In conclusion APP, a neurite-promoting molecule, is produced by OEG. Its nexin activity, dependent on the Kunitz family of serine protease inhibitors (KPI) domain and/or in combination with its glycosylation level might contribute with other factors to the ability of these cells to foster axonal elongation.

Ephrins are developmentally regulated molecules that may contribute to axonal pathfinding through their binding to Eph receptor tyrosine kinases. In many cases, ephrins act as negative molecules that stimulate growth cone collapse, although some forms may promote axonal growth. Here, we have addressed the role played by ephrin-B1 during rat postnatal cerebellar development. Ephrin-B1 is expressed by both granule and Purkinje neurons whereas EphB is present in granule neurons in early postnatal cerebellum at a time coincident with axonal and dendrite outgrowth. Stably transfected 3T3 cells overexpressing ephrin-B1 enhance survival and neurite growth from cultured cerebellar granule neurons, an effect that is inhibited by the presence of an excess of a soluble EphB protein. Ephrin-B1-induced neuritogenesis is correlated with an increased expression of certain neuronal-specific microtubule-associated proteins (MAPs). Cerebellar granule neurons plated on stably transfected 3T3 cells overexpressing ephrin-B1 show an up-regulation of the expression of axonal MAPs such as Tau and phosphorylated MAP2C compared with neurons cultured on control 3T3 cells. The level of expression of these axonal MAPs is similar to that found in neurons plated on poly-l-lysine. Interestingly, there is a noteworthy up-regulation of somatodendritic MAPs such as high-molecular-weight MAP2 and mode II-phosphorylated MAP1B in neurons cultured on stably transfected 3T3 cells overexpressing ephrin-B1 compared with neurons plated on either control 3T3 cells or poly-l-lysine. In view of these data, we suggest that ephrin-B1 favors dendritogenesis of granule neurons during cerebellum development., This work was supported by grants DGCYT, PB94-0040. M.T.M.-F. was supported by Spanish CSIC and Neurofarma contracts.

Olfactory ensheathing glia (OEG) accompany olfactory growing axons in their entry to the adult mammalian central nervous system (CNS). Due to this special characteristic, considerable attention has been focused on the possibility of using OEG for CNS regeneration. OEG present a large heterogeneity in culture with respect to their cellular morphology and expressed molecules. The specific characteristics of OEG responsible for their regenerative properties have to be defined. These properties probably result from the combination of several factors: molecular composition of the membrane (expressing adhesion molecules as PSA-NCAM, L1 and/or others) combined with their ability to reduce glial scarring and to accompany new growing axons into the host CNS. Their capacity to produce some neurotrophic factors might also account for their ability to produce CNS regeneration., Our work was supported by grants of DGCYYT and Neuropharma. M. Teresa Moreno-Flores was supported by spanish CSIC and Neuropharma contracts.

Carbapenem-resistant Acinetobacter baumannii (CRAb) is a major source of nosocomial infections in Spain associated with the production of OXA-58-like or OXA-24/40-like β-lactamase enzymes. We analysed the plasmids carrying the bla(OXA-24/40)-like gene in CRAb isolates obtained a decade apart.The presence of β-lactamases was screened for by PCR (metallo-β-lactamases, carbapenem-hydrolysing class D β-lactamases, GES and KPC) in 101 CRAb isolates obtained in two multicentre studies (GEIH/REIPI-Ab-2000 and GEIH/REIPI-Ab-2010; n = 493 Acinetobacter spp). We analysed the distribution and characterization of the plasmids carrying the bla(OXA-24/40)-like gene and sequenced two plasmids, AbATCC223p (2000) and AbATCC329p (2010) from A. baumannii ATCC 17978 transformants.Acquisition of the bla(OXA-24/40)-like gene was the main mechanism underlying resistance to carbapenems (48.7% in 2000 compared with 51.6% in 2010). This gene was mainly isolated in ST2 A. baumannii strains in both studies, although some novel STs (ST79 and ST80) appeared in 2010. The gene was located in plasmids (8-12 kbp) associated with the repAci2 or repAci2/repGR12 types. The sequences of AbATCC223p (8840 bp) and AbATCC329p (8842 bp) plasmids were similar, particularly regarding the presence of the genes encoding the AbkA/AbkB proteins associated with the toxin/antitoxin system. Moreover, the abkA/abkB gene sequences (96% identity) were also located in plasmids harbouring the bla(OXA-58)-like gene.The action of OXA-24/40 and OXA-58 β-lactamase-like enzymes represents the main mechanism underlying resistance to carbapenems in Spain in the last decade. AbkA/AbkB proteins in the toxin/antitoxin system may be involved in the successful dissemination of plasmids carrying the bla(OXA-24/40)-like gene, and probably also the bla(OXA-58)-like gene, thus contributing to the plasmid stability.

Objective To determine the safety of percutaneous dilatational tracheostomy (PDT) on hepatic allograft recipients. Patients and methods We reviewed the records of patients who underwent liver transplantation between October 2007 and April 2013, followed by PDT. In this time period, 25 liver recipients underwent PDT in our intensive care unit. We recorded severity index scores such as APACHE II and SAPS II, number of days since intubation, ratios of PaO 2 /FiO 2 (arterial oxygen pressure to fraction of inspired oxygen), coagulation study findings, complications, and procedure-related mortality rates. We compared these records with the general ICU population and literature reports. Results The median age was 58 (IC range 47–65) and 64% were men. The median time since intubation to PDT was 11 days (IC range 6.5–15.5) and from transplant to PDT 12 days. The median ratio of PaO 2 /FiO 2 was 212 (IC range 177–259). The median platelet count was 89 (IC range 37–149), significantly lower than the general ICU population (272 (IC range 186–381) P =.001). Complications were infrequent and included clinically remarkable major bleeding 8% (vs 0.3% in general ICU population; P =.005), peristomal infection of 4% and ventilator-associated pneumonia of 16% (vs 2.8% in general ICU population; P =.007). There were no deaths associated with the procedures. Conclusion PDT was tolerated well in recipients of liver allografts and had a relatively low risk of major complications and a low procedure-related mortality rate.

Fibronectin appears to be present in Senile Plaques of Alzheimer's disease brains. These senile or neuritic plaques are surrounded by dystrophic neurites, activated microglia and reactive astrocytes. The purpose of this work was to establish if a direct correlation exists between the production of Fibronectin (FN) by astrocytes and the presence of amyloid, analysing the modification of this protein produced after the treatment of cultured astrocytes with amyloid peptide (25-35). Our data showed that the addition of previously polymerised A beta-peptide to cultured astrocytes induced a marked increase in FN immunoreactivity that is in part dependent on phosphatases 2A or phosphatase 1, since was partially inhibited by okadaic acid. The increased amount of FN did not appear to be associated to any specific single isoform of which are mainly present in the rat brain. Our data suggest that in vivo FN accumulated in senile plaques may be the result, at least in part, of the response of reactive astrocyte to the presence of amyloid peptide. The importance of FN up-regulation in vivo, as part of a 'positive' response of the astrocytes to produce molecules that favours neurite outgrowth, is discussed.

We report for the first time a case of an acute disabling low-back pain episode during intravenous administration of amiodarone in a patient with atrial fibrillation. The symptoms completely resolved after terminating the infusion, and switching amiodarone from intravenous to oral administration was well tolerated.

Progressive cerebral deposition of β-amyloid peptide either in blood vessels or around neurites is one of the most important features of Alzheimer's disease (AD). The β-peptide, known as Aβ or A4, is produced by proteolytic cleavage of the amyloid precursor protein (APP). Two APP processing pathways have been proposed as physiological alternatives; only one of which leads to the production of Aβ or amyloidogenic peptides. However, we have little information regarding these processing pathways in the brain, or on whether posttranslational modifications such as glycosylation affect APP processing in vivo. Furthermore, the physiological function(s) of this protein in nervous tissue remains unclear, although modulatory roles in cell adhesion and neuritic extension have been suggested. It has been reported that APP may be glycosylated as a proteoglycan. We purified this APP population from human brain, and our data indicate that PG-APP supports neurite extension of hippocampal neurons. Neurons grown on this substratum showed an increased capacity to elongate neurites and increased neuritic “branching” compared to culture on laminin. These effects were enhanced with PG-APP samples obtained from AD brains. Our results suggest that this APP population may act as a neurite outgrowth and branching promoter and may thus play a role in some pathological conditions. These findings may have significant implications in understanding normal brain development and pathological situations (such as AD). J. Neurosci. Res. 60:87–97, 2000 © 2000 Wiley-Liss, Inc.

Alzheimer's disease (AD) is a polygenic disorder involving at least four different genes. Among them, missense mutations in the presenilins segregate with the vast majority of early onset cases of familial AD. To elucidate possible function(s) of presenilin 1 (PS1), we have studied its expression during the development of the rat nervous system. Analysis by in situ hybridization showed expression of PS1 in a variety of cell types and tissues during development, with prominent expression in the nervous system. During late embryogenesis, the ventricular zone presented the highest levels of expression, paralleling the pattern previously reported for Notch. Later, during postnatal development, we observed a peak of PS1 expression at postnatal day 10, particularly in the cerebellum and hippocampus, a time when proliferation and migration are still ongoing and synapse formation is being completed. We propose that presenilins participate in at least two different developmental processes: (1) one involved in neurogenesis and skeleton formation during embryonic development, probably involving coordinate expression with Notch, and (2) a second one in the postnatal central nervous system, perhaps involved in neuritogenic and/or synaptogenic stages, most likely playing a role in amyloid precursor protein processing and amyloid beta production.

Alzheimer's disease is characterized by an accumulation of senile or neuritic plaques surrounded by activated microglia and reactive astrocytes, the cell processes of which are frequently in contact with the amyloid core. The major component of this amyloid deposit is the amyloid peptide (betaA or betaA4). These reactive glia are characterized by their hypertrophic phenotype and by the overexpression of some molecules such as glial fibrillary acidic protein and the amyloid precursor protein (APP). The purpose of this work was to analyze whether APP expression was modified in astrocytes by the presence of betaA peptide. To study this, the effects of beta-Amyloid (25-35) on cultured astrocytes were analyzed and compared with those of a scrambled peptide. Our data indicated that the addition of previously polymerized betaA peptide induced a marked morphological change from a flat, polygonal shape to a stellated, process-bearing morphology. This change occurred with an increase in APP immunoreactivity that is dependent of phosphatases PP2A or PP1, since it was inhibited by okadaic acid. Upregulation of APP protein expression appears to be mainly nontranscriptional, because the increase of APP protein precedes the increase of mRNA expression. The analysis of several APP isoforms indicated that this increment is not due to changes of a single isoform. Our data may correlate with some in vivo reports of astrocytic APP induction after brain insult, suggesting an important role for betaA peptide in the initial process and/or maintenance of the reactive phenotype in vivo.

Amyloid beta-protein (25-35) (betaA) induced a marked morphological change in astrocytes, changing their flat polygonal shape into a stellate process-bearing morphology. The changes induced by betaA were concentration and time-dependent, whereas the addition of a scrambled peptide did not alter astrocyte morphology. We discard the possibility of betaA-astrocytes being type II-like astrocytes. We also analysed the influence of the presence of kinase and phosphate inhibitors on this morphological change. Our data indicate that the betaA-induced phenotype was not affected by the inhibition of protein tyrosine kinase or tyrosine phosphatases. Only the addition of okadaic acid to astrocytes prevented the morphological transformation from flat to stellate shape, induced by betaA (25-35). Inhibition of the stellate phenotype by okadaic acid was initiated at a concentration of 10 nM which suggested that either phosphatase 2A or 1 plays an important role in the betaA astrocytic transformation.

Nerve injuries lead to metabolic and morphological changes in the cell bodies of the neurons of origin. Increases in glucose turnover in axotomized facial and hypoglossal motor nuclei have been described. Glucose-regulated protein 78 kDa (GRP78) is implicated in cellular protein folding and subunit assembly and responds to glucose deficiency. We performed Western blot and immunohistochemistry to determine the effect of axotomy on the expression and regulation of GRP78 in the facial nucleus (FN). Facial nerve axotomy caused a larger and longer increase of GRP78 in the ipsilateral FN than in the contralateral FN. In right ipsilateral FN, axotomy resulted in elevation of GRP78 protein levels, first detected at 12 h and which reached significant, maximal induction at 24 h (75 +/- 27% increase). GRP78 protein levels decreased at later time points, but remained elevated over sham-operated controls. In contrast, no significant increase in GRP78 concentrations was found in contralateral left FN. Immunocytochemically, positive GRP78 staining was found mainly in the cytoplasm of motoneurons; there was no nuclear staining. Prominent GRP78-immunostaining appeared in axotomized motoneurons at 24 h postaxotomy as compared with the contralateral, unoperated controls. This augmentation was also observed at 4 and 7 days postaxotomy. The possibility that glucose metabolism and GRP78 levels are two parallel events in the injured facial nucleus is discussed.

The effects of β-amyloid (25–35) (βA) on cultured astrocytes from rat cortex were studied and compared with those of a scrambled peptide and with untreated cultures. Single addition (from 5 to 200 μg/ml) of βA peptide induced a marked morphological change in astrocytes, changing their flat polygonal shape into stellate process-bearing morphology. The changes induced by βA were concentration and time-dependent. The addition of the scrambled peptide did not alter cell viability in comparison with untreated astrocyte cultures. However, cell viability was dose-dependently decreased by βA. A subpopulation of βA-treated astrocytes showed an increase in glial fibrillary acidic protein (GFAP) and Vimentin (Vim) immunostaining while other reactive astrocyte markers such as S100β, MAP2, and ApoE remained unaltered or undetectable. The morphological changes in βA-treated astrocytes appeared to be mainly due to a cytoskeletal reorganization, since the total amounts of GFAP and Vim proteins were not essentially modified. These results strongly suggest that astrocytes are another cellular target of the effects of βA and this may be relevant to understanding the neuropathology of Alzheimer's disease. J. Neurosci. Res. 47:216–223, 1997. © 1997 Wiley-Liss, Inc.

Activation and proliferation of microglia are common cellular hallmarks in many different pathological processes of the central nervous system. Although a number of colony-stimulating factors enhance microglial proliferation in vitro, little is known about the endogenous mitogens. In the present study we show a strong and selective inhibition of microglial proliferation in the facial nucleus of osteopetrotic (op/op) mice, with a genetic deficiency in biologically active macrophage colony-stimulating factor (MCSF). Posttraumatic activation of adjacent axotomized neurons and reactive astrocytes was not affected, emphasizing the specificity of MCSF as a microglial growth factor.