The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Do cone age and heating mode determine the opening of serotinous cones during wildfires? A new bench scale approach applied to Pinus halepensis Mill.

Serotiny is a well-known fire adaptive trait in some species, as the Mediterranean conifer Pinus halepensis. However, information about cone opening mechanisms during wildfires and consequences on post fire dispersal is scarce. In addition, standardized methods allowing a realistic simulation of heating modes at bench-scale are not available. In this study, we address for the first time the interacting effects of radiation, convection and direct flame on the opening and seed release of serotinous cones, following a novel repeatable methodology. Using a Mass Loss Calorimeter (MLC) device and a wide range of heat exposures (between 5 and 75 kW m-2) with or without ignition, we intended to simulate realistic cone heating during surface and crown fires in laboratory conditions. Additionally, we included the effect of contrasting serotinous cone ages interacting with heating mode and considering the random individual variation. The proposed methodology has shown a high potential to simulate the complex process of crown fires in relation to cone opening under controlled conditions, detecting a threshold of heat exposure (25-30 kW m-2) for cone opening. We confirmed that heating mode had a highly significant effect in cone opening, interacting with cone age, while cone age effect on its own was marginal. Particularly, ignition significantly increased the efficacy of cone opening and seed release. Moreover, young and old cones behave differently in seed release, both in surface and crown fire simulations. Implementing and adjusting this methodology in other species will allow more realistic and reliable quantitative comparisons than previously attained.

Neuroglial patterns are shared by cerebella from prion and prion-like disorder affected patients.

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are considered prion-like disorders because they are all proteinopathies in which aberrant proteins spread throughout the brain during disease progression. The overall aim of this study is to determine how glial cells are commonly involved in the neurodegeneration progress observed in all these pathologies. The suggestion that they are cell types in which prion and prion-like disorders have common behaviour is the hypothesis on which this study is based. Morphological and distribution differences in astroglial and microglial cells in the cerebellum from prion and prion-like disease-affected patients were assessed here by histopathological and immunochemical tools. To our knowledge, this is the first study to focus on the comparative assessment of glial profiles in these human brains. Activated microglial population was demonstrated in both, prion and prion-like disorders, although in higher extent in the first. In astroglial activation, specific patterns of alterations suggesting both degenerative and potentially neuroprotective or restorative stem cell response, were shown to be alternatively shared by cerebella from all disorders studied. Neuro-protective strategies for these disabling disorders are particularly desirable.

Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.

Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-ß3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.

Short-term effects of prescribed burning on litterfall biomass in mixed stands of Pinus nigra and Pinus pinaster and pure stands of Pinus nigra in the Cuenca Mountains (Central-Eastern Spain).

Fire severity, defined as the magnitude of fire effects in an ecosystem, is a key factor to consider in planning management strategies for protecting forests against fire. Although prescribed burning has been used as a fuel reduction tool in forest ecosystems, it is quite limited in the Mediterranean region. Furthermore, little is known about how tree crowns are affected by prescribed underburning aimed at reducing fire severity in conifer stands. As part of an ongoing study to assess the effects of prescribed burning on the tree canopy, litterfall is currently being monitored in a network of experimental plots located in mixed (Pinus nigra and Pinus pinaster) and pure (P. nigra) conifer stands in the Cuenca Mountains (Castilla La Mancha, Spain). A total of 12 study plots (30m×30m) were established in a completely randomized experimental design to determine the effect of burning, with 2 treatments: no burning (control) and burning (i.e. with three replicate plots for each treatment and site). Burning was conducted in May 2016. In each plot, 8 litterfall collectors were installed at regular intervals, according to international protocols (ICP Forests), and all biomass falling into the collectors is being monitored monthly. The specific objective of this study is to assess how prescribed burning affects the rate of generation of foliar and non-foliar litterfall biomass due to the fire. In addition, the Leaf Area Index was estimated before burning and one year later to verify possible changes in the structure of the stands. This information could be used to help minimize the negative impacts of prescribed underburning on litterfall. To our knowledge, this study represents the first attempt to evaluate the effect of prescribed burning on litterfall biomass in Europe.

The value of cone beam computed tomography imaging in surgically assisted rapid palatal expansion: a systematic review of the literature.

This study aimed to evaluate the reliability of cone-beam computed tomography (CBCT) imaging of the maxillary structures and the postoperative dentoskeletal, nasal airway, periodontal, and facial soft tissue changes after surgically assisted rapid palatal expansion (SARPE). A systematic review of the literature on CBCT analysis of SARPE was performed. The PubMed, Embase, and Cochrane Library databases were searched. Nine articles were included, involving a total of 228 patients. The general trend was tooth-borne distraction with pterygomaxillary dysjunction. A systematic increase in all transverse dimensions at the dentoalveolar and dental levels, as well as a certain degree of tipping and extrusion of the anchorage teeth and tipping of the skeletal segments, was detected. Soft tissue findings reflected the underlying dentoalveolar changes. A decrease in the buccal alveolar bone thickness and alveolar crest level occurred. Results confirm that CBCT is an accurate and reliable method to assess anatomical changes after SARPE. Although this systematic review provides valuable preliminary information about the effects of SARPE, results should be interpreted with caution due to the low level of evidence of the publications, great heterogeneity among study groups regarding outcome variables and surgical-orthodontic protocols, and lack of long-term data.

Hiperandrogenismo secundario a tumor suprarrenal: causa rara a tener en cuenta / Hyperandrogenism secondary to suprarrenal tumor: rare cause to take into account

Se conoce como hiperandrogenismo al exceso de andrógenos en la mujer. Una causa poco frecuente de hiperandrogenismo consiste en la presencia de tumores de la corteza suprarrenal productores de andrógenos, siendo la mayoría de ellos malignos. Se exponen 2 casos de tumores suprarrenales productores de andrógenos con diagnóstico final de adenomas a pesar de la presencia inicial de distintos datos que orientaban a una naturaleza maligna (AU)

The excess of androgen in women is known as hyperandrogenism. A rare cause of hyperandrogenism consists of the presence of tumors, mostly malignant tumors, in the adrenal cortex that produces androgens. We present two adrenal tumoral cases that produce androgen with adenoma final diagnosis in spite of the initial presence of several data oriented towards a malignant nature (AU)

Possible land management uses of common cypress to reduce wildfire initiation risk: a laboratory study.

Accurate determination of flammability is required in order to improve knowledge about vegetation fire risk. Study of the flammability of different plant species is essential for the Mediterranean area, where most ecosystems are adapted to natural fire but vulnerable to recurrent human-induced fires, which are the main cause of forest degradation. However, the methods used to evaluate vegetation flammability have not yet been standardized. Cupressus sempervirens is a native or naturalized forest tree species in the Mediterranean area that is able to tolerate prolonged drought and high temperatures. The aim of this study was to characterize the flammability of C. sempervirens var. horizontalis at particle level by using different bench-scale calorimetry techniques (mass loss calorimeter, epiradiator and oxygen bomb) to determine the main flammability descriptors (ignitability, sustainability, combustibility and consumability) in live crown and litter samples. Our findings indicate that this variety of cypress is relatively resistant to ignition because of the high ash content, the high critical heat flux, the high time to ignition displayed by both crown and litter samples and the ability of the leaves to maintain a high water content during the summer. We also discuss the possibility of exploiting some morphological, functional and ecological traits of the species to construct a barrier system (with selected varieties of cypress) as a promising complementary land management tool to reduce the fire spread and intensity in a Mediterranean context.

The effects of physical exercise in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis of randomized control trials.

OBJECTIVE: The aim of this systematic review and meta-analysis was to examine the evidence for the effectiveness of exercise interventions on attention deficit hyperactivity disorder (ADHD)-related symptoms such as inattention, hyperactivity/impulsivity, anxiety and cognitive functions in children and adolescents. METHOD: Five databases covering the period up to November 2014 (PubMed, Scopus, EMBASE, EBSCO [E-journal, CINAHL, SportDiscus] and The Cochrane Library) were searched. Methodological quality was assessed using the Cochrane tool of bias. Standardized mean differences (SMD) and 95% confidence intervals were calculated, and the heterogeneity of the studies was estimated using Cochran's Q-statistic. RESULTS: Eight randomized controlled trials (n = 249) satisfied the inclusion criteria. The studies were grouped according to the intervention programme: aerobic and yoga exercise. The meta-analysis suggests that aerobic exercise had a moderate to large effect on core symptoms such as attention (SMD = 0.84), hyperactivity (SMD = 0.56) and impulsivity (SMD = 0.56) and related symptoms such as anxiety (SMD = 0.66), executive function (SMD = 0.58) and social disorders (SMD = 0.59) in children with ADHD. Yoga exercise suggests an improvement in the core symptoms of ADHD. CONCLUSIONS: The main cumulative evidence indicates that short-term aerobic exercise, based on several aerobic intervention formats, seems to be effective for mitigating symptoms such as attention, hyperactivity, impulsivity, anxiety, executive function and social disorders in children with ADHD.

Crop row detection in maize fields inspired on the human visual perception.

This paper proposes a new method, oriented to image real-time processing, for identifying crop rows in maize fields in the images. The vision system is designed to be installed onboard a mobile agricultural vehicle, that is, submitted to gyros, vibrations, and undesired movements. The images are captured under image perspective, being affected by the above undesired effects. The image processing consists of two main processes: image segmentation and crop row detection. The first one applies a threshold to separate green plants or pixels (crops and weeds) from the rest (soil, stones, and others). It is based on a fuzzy clustering process, which allows obtaining the threshold to be applied during the normal operation process. The crop row detection applies a method based on image perspective projection that searches for maximum accumulation of segmented green pixels along straight alignments. They determine the expected crop lines in the images. The method is robust enough to work under the above-mentioned undesired effects. It is favorably compared against the well-tested Hough transformation for line detection.

p38α limits the contribution of MAP17 to cancer progression in breast tumors.

MAP17 is a small, 17-kDa, non-glycosylated membrane protein that is overexpressed in a percentage of carcinomas. In the present work, we have analyzed the role of MAP17 expression during mammary cancer progression. We have found that MAP17 is expressed in 60% human mammary tumors while it is not expressed in normal or benign neoplasias. MAP17 levels increased with breast tumor stage and were strongly correlated with mammary tumoral progression. A significant increase in the levels of reactive oxygen species (ROS) was observed in MAP17-expressing cells, as compared with parental cells. This increase was further paralleled by an increase in the tumorigenic capacity of carcinoma cells but not in immortal non-tumoral breast epithelial cells, which provides a selective advantage once tumorigenesis has begun. Expression of specific MAP17 shRNA in protein-expressing tumor cells reduced their tumorigenic capabilities, which suggests that this effect is dependent upon MAP17 protein expression. Our data show that ROS functions as a second messenger that enhances tumoral properties, which are inhibited in non-tumoral cells. We have found that p38α activation mediates this response. MAP17 triggers a ROS-dependent, senescence-like response that is abolished in the absence of p38a activation. Furthermore, in human breast tumors, MAP17 activation is correlated with a lack of phosphorylation of p38α. Therefore, MAP17 is overexpressed in late-stage breast tumors, in which oncogenic activity relies on p38 insensitivity to induce intracellular ROS.

Creación de un trípticodestinado a los padres de reciénnacidos para la prevención de laplagiocefalia postural / Elaboration of a 3-page brochure aimed at the parents of newborns for the prevention of postural plagiocephaly

En 1992, la Academia Americana de Pediatría lanzó la campaña “Backto sleep” para la prevención de la muerte súbita del lactante, con la recomendaciónde poner a los bebés a dormir tumbados boca arriba. Estapropuesta ha resultado eficaz para la prevención de la muerte súbita,que se ha reducido en un 40%, pero como consecuencia negativa ha generadoun aumento considerable de los casos de plagiocefalia posturalo deformidad craneal debido a la postura. La clave para una evoluciónfavorable del lactante con una deformidad craneal posicional es el diagnósticoy el tratamiento precoz, por ello, desde la consulta de Enfermeríapediátrica del Centro de Salud Gazalbide de Vitoria-Gasteiz, se decidióllevar a cabo una intervención de educación sanitaria con el objetivode informar y enseñar a los padres en la prevención de la DeformidadCraneal Postural (DCP) desde los primeros 15 días de vida del niño hastapasados los seis meses. Para ello, se elaboró un pequeño tríptico coninstrucciones para facilitar la labor de los progenitores y para ayudarlesa tomar conciencia de la importancia que tienen estas pequeñas accionescotidianas para sus hijos. Después de un año realizando este trabajo,el resultado es que, salvo pequeñas excepciones, los niños atendidosen ese período de 0 a 1 año no presentan signos significativos de plagiocefaliapostural (AU)

In 1992, the American Academy of Paediatrics launched a campaigncalled Back to Sleep for the prevention of sudden infant death syndrome,with the recommendation of putting infants on their backs and faceup for sleep. This recommendation has proven to be effective to preventsudden infant death that has been reduced by a 40%. However, a negativeconsequence of this measure has generated a considerable increasein the number of cases of postural plagiocephaly or cranial deformitycaused by posture. The key for a favourable outcome of the infant witha positional head deformity is early diagnosis and treatment. Becauseof this, from the paediatrics office of the Gazalbide health centre of Vitoria-Gasteiz, it was decided to conduct a health education interventionwith the aim of informing and training parents on the prevention of PosturalCranial Deformity (PCD) from the first 15 days of life of the infantuntil past the six months of life. For this purpose, a small brochure wasdeveloped with instructions to facilitate the work of the parents and tohelp them to become aware of the importance that these little daily actionshave on their children. After one year of implementation of thiswork, the results show that, with few exceptions, the children followedup in that period of time from 0 to 1 year of age do not present significantsigns of postural plagiocephaly (AU)

Estudio descriptivo de las desintoxicaciones de alcohol en un Servicio de Medicina Interna / No disponible

La dependencia al alcohol es una enfermedad crónica y su tratamiento comienza con la desintoxicación, continuándose con la rehabilitación. Se presenta un estudio descriptivo y retrospectivo de las desintoxicaciones de alcohol en 147 pacientes ingresados en nuestra unidad en el periodo 2003-2005. La media de edad es de 46.07 años, 77.6% hombres y 22.4% mujeres. Ingreso por síndrome de deprivación alcohólica en 31 pacientes (21.1%), desintoxicación programada en 116 pacientes (78.9%). Según la escala CIWA-Ar: abstinencia grado leve 100 pacientes (68.5%), moderada35 (24%), grave 11 (7.5%). La estancia media global fue de 11.5 días, sin diferencias estadísticamente significativas. Grupo Leve con proporción significativamente menor de hepatopatía, grupos Moderado y Grave proporción significativamente alta. Al compararla media de la edad, estancia, cantidad de alcohol y parámetros de consumo crónico (ferritina, fe, VCM, UBE, GPT, GGT, bilirrubina y Mg), se encuentran diferencias significativas entre las medias de los grupos Leve y Grave para la GPT y bilirrubina total. Se produjeron crisis epilépticas en 11 pacientes, 4 pertenecían al grupo programado,7 con intensidad moderada-grave. No se ha evidenciado relación entre la intensidad del síndrome de deprivación, edad y sexo. Mayor intensidad en la escala CIWA-Ar (grados moderado y grave) entre los pacientes con síndrome de deprivación ya iniciado comparados con los ingresados programados, que predominantemente presentaban un grado leve. La CIWA-Ar es un instrumento útil para evaluar los síntomas de deprivación, el riesgo de complicaciones y planificar el tratamiento. La actitud clínica debe facilitar el acceso del paciente a los recursos sanitarios para el tratamiento de su adicción, normalizando la asistencia durante el ingreso hospitalario

Alcohol dependence is a chronic disease whose treatment begins with detoxification, followed by rehabilitation. We present a descriptive and retrospective study of 147 patients admitted to our unit during the period 2003-2005. Median age was 46.07 years, with 77.6% men and 22.4% women. Admission diagnosis was alcohol with drawal syndrome in 31 patients (21.1%) and programmed alcohol detoxification in 116 patients (78.9%). On the CIWA-Ar scale: mild withdrawal, 100 patients (68.5%), moderate, 35 patients (24%), severe, 11 patients (7.5%). Mild group showed a statistically significantly lower proportion of hepatopathy, by comparison with the moderate and severe groups. Statistically significant differences were found between the mild and severe groups on comparing mean age, duration of stay, quantity of alcohol and parameters of chronic consumption (ferritine, fe, VCM, UBE,AST, bilirubin and Mg) for AST and bilirubin. There were 11 seizures: 4 patients from the programmed group, with mild with drawal on the CIWA-Ar scale, and 7 patients with moderate-severe with drawal. No relationship was found between patients’ intensity of with drawal syndrome, age or sex. There was higher intensity on the CIWA-Ar score (moderate and severe) among patients who had already begun with drawal syndrome, compared to those admitted on a planned detoxification programme. The CIWA-Ar is a useful tool for assessing with drawal symptoms and risks of complication and for planning treatment. Clinical practice must provide patients with access to health resources for the appropriate treatment of their addiction, with standardized assistance during their stay in hospital

Bone mass in young adults with Down syndrome.

BACKGROUND: Down syndrome (DS) is a frequent cause of intellectual disability. With the increasing life expectancy of these patients, concerns have been raised about the risk of osteoporosis. In fact, several investigators have reported a reduced bone mass in DS. However, the results may be confounded by comorbid diseases, and differences in lifestyle habits and body size. Therefore, we planned to determine anthropometric and lifestyle factors influencing bone mineral density (BMD) in young adults with DS. METHODS: Thirty-nine patients with DS (mean age 26 years) and 78 controls were studied. Areal BMD was measured by dual x-ray densitometry (DXA); volumetric BMD at the lumbar spine and femoral neck was estimated with published formulae. RESULTS: DS patients had lower areal BMD than controls at all regions (spine, hip and total body). Height and projected bone area were also lower. There were no differences between both groups regarding estimated volumetric BMD at the femoral neck. However, spine volumetric BMD was also lower in DS than controls. In multivariate analysis, DS, male sex, little physical activity and low sunlight exposure were associated with lower spine volumetric BMD; on the other hand, fat mass and sunlight exposure were associated with femoral neck volumetric BMD. CONCLUSION: This study shows that patients with DS had a reduced areal BMD, but it is in part a consequence of the reduced body size, particularly at the femoral neck. Physical activity and sunlight exposure are associated to volumetric BMD and should be stimulated in order to maintain an adequate bone mass in these patients.

Cellular senescence bypass screen identifies new putative tumor suppressor genes.

Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. To identify new senescence regulatory genes that might play a role in tumorigenesis, we have designed and performed a large-scale antisense-based genetic screen in primary mouse embryo fibroblasts (MEFs). Out of this screen, we have identified five different genes through which loss of function partially bypasses senescence. These genes belong to very different biochemical families: csn2 (component of the Cop9 signalosome), aldose reductase (a metabolic enzyme) and brf1 (subunit of the RNA polymerase II complex), S-adenosyl homocysteine hydrolase and Bub1. Inactivation, at least partial, of these genes confers resistance to both p53- and p16INK4a-induced proliferation arrest. Furthermore, such inactivation inhibits p53 but not E2F1 transcriptional activity and impairs DNA-damage-induced transcription of p21. Since the aim of the screen was to identify new regulators of tumorigenesis, we have tested their inactivation in human tumors. We have found, either by northern blot or quantitative reverse transcriptase-PCR analysis, that the expression of three genes, Csn2, Aldose reductase and Brf1, is lost at different ratios in tumors of different origins. These genes are located at common positions of loss of heterogeneity (15q21.2, 7q35 and 14q32.33); therefore,we have measured genomic losses of these specific genes in different tumors. We have found that Csn2 and Brf1 also show genomic losses of one allele in different tumors. Our data suggest that the three genes identified in the genome-wide loss-of-function genetic screen are putative tumor suppressors located at 15q21.2; 7q35 and 14q32.33.

Sporadic invasive breast carcinomas with medullary features display a basal-like phenotype: an immunohistochemical and gene amplification study.

It is not clear whether invasive breast carcinomas with medullary features (IBCMFs, atypical medullary carcinomas) constitute a specific phenotype of breast cancer that is of biologic significance. Because medullary features are common in BRCA1-associated carcinomas and these tumors frequently show a basal-like phenotype, we examined whether IBCMFs expressed basal/myoepithelial markers and had a basal-like phenotype. We studied the immunohistochemical expression of 15 markers in tissue microarrays containing samples from 35 IBCMFs and 39 grade 3 invasive ductal carcinomas (IDCG3s) of no special type. In addition, we analyzed EGFR, C-MYC, and CCNE gene amplification by fluorescence in situ hybridization, because the expression of these genes is known to be associated with the basal-like phenotype. We defined the basal-like phenotype according to the criteria of Nielsen et al as being those tumors that were ER/HER2-negative and cytokeratin (CK) 5/6- and/or epidermal growth factor receptor-positive. IBCMFs were more frequently hormone receptor- and HER2-negative, but had greater expression of proliferation markers and p53. In addition, IBCMFs more frequently expressed basal/myoepithelial markers, such as CK5/6 and P-cadherin. A basal-like phenotype was found in 62.9% of IBCMFs but in only 18.9% of IDCG3s. No differences in gene amplification were found between IBCMFs and IDCG3s, although C-MYC amplification was more common in tumors without a basal-like phenotype. The identification of IBCMF as an independent group of tumors could be of clinical significance, given the high incidence of cases with a basal-like phenotype, which is a group of tumors with different prognosis and chemotherapy response from those of IDCG3s of no special type.

Pseudoaneurisma de arteria femoral profunda secundario a osteosíntesis de una fractura proximal de fémur. Presentación como complicación tardía / Deep femoral artery pseudoaneurysm secondary to osteosynthesis of a proximal femoral fracture. Condition occurring as a late complication

Introducción. El diagnóstico de pseudoaneurisma de la arteria femoral profunda como complicación tras la osteosíntesis del fémur proximal es poco frecuente. Su presentación de forma tardía es excepcional, aumentando la dificultad de su diagnóstico. Caso clínico. Se presenta el caso de un varón de 40 años que tras precipitación presenta fractura subcapital de fémur izquierdo desplazada en varo. Se procedió a la reducción cerrada de la fractura y osteosíntesis mediante tornillo dinámico de cadera. Su evolución inicial fue satisfactoria. A las ocho semanas el paciente reingresó por dolor a nivel del muslo izquierdo. Tras estudio mediante arteriografía se llegó al diagnóstico de pseudoaneurisma y rotura de la rama anastomótica magna de la arteria femoral profunda, procediéndose a su embolización selectiva. Conclusión. La presentación diferida del pseudoaneurisma de la arteria femoral profunda es poco frecuente. Puede cursar de forma subclínica por lo que para su diagnóstico precoz debemos mantener un alto nivel de sospecha

Introduction. Diagnosis of deep femoral artery pseudoaneurysm as a complication of proximal femoral osteosynthesis is unusual. Late presentation of this condition is exceptional and increases the difficulty of its diagnosis. Clinical case. A 40-year-old man presented a subcapital left femur fracture with varus displacement caused by a fall. A dynamic hip screw was used for osteosynthesis to achieve closed reduction of the fracture. Initial evolution was satisfactory. Eight weeks later the patient was hospitalized due to left thigh pain. An arteriography was performed and a pseudoanerysm together with the rupture of the greater anastomotic branch of the deep femoral artery were diagnosed. Selective embolization was carried out. Conclusion. Late presentation of deep femoral artery pseudoanerysm is infrequent. As it may evolve subclinically, it is necessary to keep it in mind for an early diagnosis

Large scale genetic screen identifies MAP17 as protein bypassing TNF-induced growth arrest.

Although activated macrophages destroy cancer cells more effectively than normal cells, the ability to escape activated macrophages is a characteristic of tumor cells. One of the mechanisms responsible for the specific killing of tumor cells by macrophages is the production of the cytokine tumor necrosis factor (TNF) alpha. Therefore, resistance to TNF may provide such cancer cells a selective advantage against host elimination. With the aim of identifying genes with these properties we undertook a large scale genetic screen to identify genes able to bypass TNF-induced G1 arrest. We identified MAP17, a small 17 kDa nonglycosylated membrane protein that localizes to the plasma membrane and the Golgi apparatus. Ectopic expression of MAP17 in tumor cells prevents TNF-induced G1 arrest by impairing p21waf1 induction. However, expression of MAP17 does not inhibit TNF-induced apoptosis in Me180-sensitive tumor cells. The inhibition of TNF is specific since MAP17 does not alter the response to other cytokines such as IFNgamma. As described in the Xenopus oocyte system, MAP17 increases the uptake of mannose in some cells, but this effect is not responsible for TNF bypass. We have also analyzed the expression of MAP17 mRNA in a panel of cell lines. MAP17 is expressed in 30% of cell lines of different origin. However, MAP17 mRNA expression did not correlate with TNF resistance. Our data indicates that although MAP17 expression might bypass TNF-induced growth arrest, it is not the only determinant of this response.

High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline.

An automatic data-collection system has been implemented and installed on seven insertion-device beamlines and a bending-magnet beamline at the ESRF (European Synchrotron Radiation Facility) as part of the SPINE (Structural Proteomics In Europe) development of an automated structure-determination pipeline. The system allows remote interaction with beamline-control systems and automatic sample mounting, alignment, characterization, data collection and processing. Reports of all actions taken are available for inspection via database modules and web services.

Automation of sample mounting for macromolecular crystallography.

A standard sample holder and vial for cryocooled macromolecular crystals has been defined for use with robotic sample changers. This SPINE standard sample holder is a modified version, with added features and specifications, of sample holders in common use. In particular, the SPINE standard meets the precision required for automatic sample exchange and includes a cap that is identified by a two-dimensional datamatrix code as well as an optional vial. At the ESRF, the sample holder standard is in use with the EMBL/ESRF/BM14 robotic sample changer (SC3) which is installed on eight beamlines. The SC3 can hold up to 50 crystals stored in five baskets. A datamatrix reader in the SC3 ensures safe management of the sample flow and facilitates fully automatic screening and characterization of samples. Tools for handling and transporting 50 samples in a dry shipping dewar have been developed. In addition to the SC3, the SPINE sample holder is currently compatible with a number of other robotic sample changers.