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Resumen Introduccion Los resultados de la reparacion de la hernia paraestomal (HP) basados en datos provenientes de registros son escasos. El objetivo del presente trabajo es analizar los datos recogidos sobre la HP en el Registro Nacional de Hernia Incisional (EVEREG) y asi evaluar las practicas actuales y resultados en la reparacion de una HP. Metodos Se analizan los datos de la cohorte de HP registradas en el periodo desde julio de 2012 hasta junio de 2018. Se analizan las complicaciones, recidivas y factores asociados a ellas de la cohorte completa de HP, independientemente del tipo de estoma al que se asocian. Posteriormente, se realiza el mismo analisis del grupo de HP con relacion a una colostomia (grupo mas numeroso). Resultados Se estudiaron 353 HP. De estas, 259 (73%) fueron HP en el contexto de una colostomia terminal, 74 (21%) en el de una ileostomia terminal y 20 (6%) en el de una ureteroileostomia (Bricker). La edad media global fue de 68,7 ± 11,1 anos y 135 (38%) pacientes fueron del sexo femenino. El abordaje abierto y la cirugia electiva fueron predominantes (78% y 92%, respectivamente). El 99% se reparo con una malla sintetica no absorbible. Las complicaciones postoperatorias globales fueron altas (30,6%), asi como la recurrencia global (27,5%) tras un seguimiento medio de 9,4 meses. Conclusiones La reparacion de la HP es poco frecuente comparada con el conjunto de reparaciones de la hernia incisional. La cirugia de la HP parece relacionarse con un porcentaje elevado de complicaciones postoperatorias y recidiva.

Devices that increase the penetration of intravesical chemotherapeutic agents have been developed as alternatives to the use of bacillus Calmette-Guérin, in short supply at a time of increasing global incidence of non-muscle invasive bladder cancer (NMIBC). We performed a prospective observational study to compare 2 of these devices in the treatment of patients with high- and intermediate-risk NMIBC. The primary endpoint was the recurrence-free rate. Secondary endpoints were the rate of progression and adverse events.After undergoing transurethral bladder resection, 98 patients were selected to receive 1 of 2 treatments: hyperthermic intravesical chemotherapy (HIVEC) treatment with 40 mg of mitomycin C (MMC) using Combat BRS System V2.0 at 43 ± 0.5°C and 200 ml/min for 60 minutes (56 patients) or electromotive drug administration (EMDA) with 40 mg of MMC at 20 mA for 30 minutes (42 patients). The treatment schemes were similar: 6 weekly instillations as induction and 6-monthly instillations as maintenance. The recurrence rates were evaluated at 6 and 12 months and the progression rates at 12 months.The recurrence-free rate at 12 months was 91,1% in the HIVEC group and 88.1% in the EMDA group (P ≥ 0.05). After the 12-month follow-up, only 1 progression occurred in each treatment group. In terms of adverse events, no significant differences were found between the treatments.HIVEC and EMDA techniques are comparable in terms of recurrence, progression and adverse events at 12 months in the treatment of patients with high- and intermediate-risk NMIBC.

Nowadays, simulators are used in different applications, such as benchmarking tools, for entertainment and educational purposes, to test scenarios that otherwise would not be possible to analyze (e.g., for security reasons) or to evaluate business and regulatory models. Nevertheless, simulators are usually tailor-made for a specific application. This paper proposes an original approach, an architecture for a software tool capable of simulating any electric power system application, the first energy-oriented meta-simulator. This tool would only require the definition of a set of behavior rules, easing the process of developing new simulators aimed at the energy sector. Its applications range from pure software simulators, that could be used with, for example, benchmarking, decision-making or competition purposes, to applications monitoring and controlling energy assets in real-time, such as hardware devices (e.g., sensors, actuators, or power plants) or digital twins. The proposed architecture resulted by studying previous tools and simulators with the objective of finding common blocks and elements to abstract them. For this reason, the proposed architecture intents to encompass any tool that aims to model the energy sector. Additionally, the proposed architecture is compliant with lightweight Internet of Things (IoT) protocols and smart systems and supports the synchronization with other frameworks at different levels.

Background & Aims People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. Methods The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. Results Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%–96%) never injectors, 673 (92%, 95% CI 89%–93%) PWID not on OAT and 177 (89%, 95% CI 83%–92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p Conclusions HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. Lay summary Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.

Anocolumnar titanium coatings have been fabricated in two sputtering systems with very different characteristics (a laboratory setup and semi-industrial equipment), thus possessing different morphologies (150 nm long columns tilted 20° from the normal and 300 nm long ones tilted 40°, respectively). These coatings exhibit similar antibacterial properties against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli) bacteria. When a synergic route is followed and these coatings are functionalized with tellurium (Te) nanorods, the antibacterial properties are enhanced, especially for the long nanocolumns case. The biocompatibility is preserved in all the nanostructured coatings., Funding from MINECO (MAT2014-59772-C2-1-P, MAT2014-59772-C2-2-P and MAT2011-29194-C02-02) and Fundación Domingo Martínez is acknowledged. J.M. G.-M. thanks MECD (PRX16/00383) and Fulbright Commission for his stay at Northeastern University. We also acknowledge the service from the MiNa Laboratory at IMN funded by CM (S2013/ICE2822), MINECO (CSIC13-4E-1794) and the EU (FEDER, FSE).

We have studied nanometric high aspect ratio Ag nanopillar coatings exhibiting reduced secondary electron emission for the mitigation of multipactor effect in radio-frequency space devices of high frequency and high power. The Ag nanopillars have been grown by glancing angle deposition with DC magnetron sputtering. Some samples have been covered by a gold capping layer to reduce oxidation and aging effects. The secondary emission yield of the surfaces of these samples has been measured and compared to those of flat Ag and Au reference samples. The results show that high aspect ratio surface roughness at the nanometer scale significantly reduce the secondary emission yield of the surface. This reduction is more important for low electron energies, which is the most influencing energy range of electrons for multipactor. The multipactor region for the nanopillar coating presenting the best secondary emission yield properties has been simulated, finding practical suppression of multipactor effect. The high-frequency surface resistance of these samples has also been estimated from published computations for similar surface roughness patterns. It was found that such nanopillar coatings are compatible with the best accomplishments of present space industry., This investigation has been funded by the MINECO of Spain through the AYA2012-39832-C02-02, FIS2015-67367-C2-1-P, MAT2015-69035-REDC and MAT2014-59772-C2-1-P projects and by the Comunidad de Madrid through the NANOMAGCOST-CM Ref: P2018/NMT4321 project. One of the authors (C.M.) thanks MECD for FPU14/02020 grant. The authors also want to thank SEGAINVEX and SIdI from UAM for technical support, and to acknowledge the service from the MiNa Laboratory at IMN funded by Comunidad de Madrid (S2018/NMT-4291 TEC2SPACE), MINECO (CSIC13-4E-1794) and the European Union (FEDER, FSE).

Background Nonoperative management of proximal humeral fractures (PHFs) is the most common treatment, but its functional outcome may improve with early mobilization. In frail osteoporotic patients, quick recovery of prefracture independency is mandatory. This study assessed fracture displacement in PHFs managed with conservative treatment after early mobilization and a home-based self-exercise program. Methods We retrospectively analyzed the radiologic displacement of fracture fragments of PHFs treated conservatively with early mobilization and a home-based self-exercise program. Results Included were 99 patients with 26 one-part, 32 two-part, 32 three-part, and 9 four-part PHFs managed conservatively, followed by early mobilization and a home-based self-exercise program. In the x-ray examinations, the head displaced from varus into valgus 55° ± 23° to 42° ± 22°, in the normal range of anatomic values. The medial hinge displaced from medial to the diaphysis (+1 ± 6 mm) to lateral to the head (−0.6 ± 6 mm). The greater tuberosity displaced cranially from −1 ± 7 mm to 2 ± 5 mm. The Constant score at the 1-year follow-up was 79.69 ± 16.3. Discussion and conclusions The home-based self-exercise program for conservative treatment of PHFs displaces the head-diaphysis angle and the medial hinge toward anatomic reduction, but there is a risk of greater tuberosity cranial displacement. Functional results are fairly good, allowing frail patients to keep on with their independency and life style. Because a large number of patients might need further physiotherapy, the quality of the home-based self-exercises should be supervised.

espanolObjetivos Las valoraciones del alumnado permiten identificar cambios necesarios en la organizacion y contenidos de las practicas clinicas. El objetivo del Programa Institucional de Evaluacion fue disenar y validar un instrumento para capturar sus valoraciones de la ensenanza practica en traumatologia. Metodo Profesores de la unidad docente de Cirugia Ortopedica y expertos en calidad educativa elaboraron una propuesta inicial de dimensiones a explorar, y se diseno un estudio de campo para determinar consistencia y validez de construccion y predictiva. Resultados Los resultados (alfa de Cronbach; 0,58; correlaciones item-total: > 0,5; Eigenvalues: > 0,6; saturaciones factoriales y T-test) verifican la consistencia y validez del instrumento. Conclusiones Este instrumento permite capturar la experiencia del alumnado con fiabilidad y validez. El uso sistematico de un instrumento como este contribuye a la calidad de la ensenanza. EnglishObjectives The experience of students contributes to proactively identifying the changes necessary in training approaches and activities. The main objective of the Institutional Evaluation Programme was to design and validate a tool that permits discerning the experience of students from traumatology teaching. Methods Lecturers from the Orthopaedic Surgery Teaching Unit and experts in quality evaluation methodology, prepared the initial items. In this study, a descriptive analysis was carried out first, followed by an analysis of internal consistency and reliability, construction validity, and predictive validity. Results The results (Cronbach's alpha = 0.58, Inter-Item Correlations >0.5, Eigenvalues >0.6, factor loadings, and the Student t-test values) confirmed its reliability and validity. Conclusions The developed scale is reliable and valid to assess the experience of students. The use of a tool with these characteristics systematically contributes to improve teaching quality.

Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C > T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus., This work was supported by grants from: 1) the “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III”: PI10/0703, PI13/00556 and PI16/00789 to RG and PI15/00484 to MEG cofunded by FEDER, 2) from the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER): grants 13-717/132.05 and ER16P3AC717 to RG and 3) “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to RG). MDCOC receives grant support from CIBERER and FZD from the Ministerio de Educación, Cultura y Deporte (FPU13/00544). MEG is supported by a “Miguel Servet contract” (CP16/00046) from ISCIII-MINECO-Spain/FEDER-EU.

Parent material is a soil forming factor which, specially in temperate climates, influences soil hydraulic properties. As direct measurements of the soil hydraulic properties are laborious, time-consuming and expensive, this work explores the influence of geological material on soil hydraulic properties using the Balanced Entropy Index (BEI) as a particle size distribution descriptor which was shown to be useful in the estimation of soil water retention properties. The studied geological materials correspond to the phyllites, quartz-phyllites, metagreywackes, quartzites, schists and granites in the Northern part of Portugal. The source of information used to carry out this study was the soil map of the studied region, scale 1/25,000. Non-parametric Kruskal-Wallis tests, followed by multiple comparisons between pairs of group medians using Bonferroni significant differences (BSD), were applied to determine if soil texture heterogeneity, measured using the BEI, significantly varied between the lithological groups under study. Results clearly show how the type of rock controls the BEI of the overlying soils in the studied area. Further implications of this result are discussed in the text.

Using the Shannon Information Entropy (IE) as a soil structure metric is proposed to analyze the effect of the particle size distribution (PSD) heterogeneity on soil bulk density values. A data base including 6239 soil samples from Florida is used. For each soil the IE is computed using mass proportions of the seven texture fractions that the data base provides. The range of IE values is divided into subintervals of equal length to study how differences in the soil texture metric are reflected in differences in soil bulk density values. The total range of IE values divided into equal subintervals, each subinterval corresponds to the group of soils with IE in this subinterval, average bulk density for soils in each subinterval is found, and the average information entropy value in any of the subintervals is plotted versus the average soil bulk density values. Coefficients of determination of the linear regressions ‘average IE vs. average bulk density’ were 0.99 and 0.98 for 10 and 15 subintervals respectively. Predictions based in that linear relationship give the mean predicted error (MPE) equal to 0.0015 g/cm3 over the total number of soils, and the normal distribution of prediction errors with the standard deviation of to 0.16 g/cm3. These results strongly support the hypothesis that Information Entropy can serve as an indicator of the typical bulk density for a soil with a given PSD. Values of IE were also computed for all samples in the database using only three texture fractions: clay, silt and sand content. Simple linear regression using the IE value as the input variable was implemented to predict bulk density value. Additionally, several published bulk density pedotransfer functions (PTFs), including organic carbon (OC) content and texture inputs, were applied to the same data base. Results show the root-mean-squared error of predictions close to 0.16 g/cm3 when the IE is used as the sole input. Estimation of bulk density using Information Entropy as predictor became worse for soils in horizon A than in the horizon E, respectively, possibly due to the influence of the different organic carbon content in those horizons. Overall, the Information Entropy metric of soil texture provides a useful input for estimating bulk density, which also might be used together with other inputs as depth or OC content.

[Objective]: To demonstrate that patients with Xp11.2/TFE3 gene-fusion translocation renal cell carcinoma (RCC), despite having an aggressive course in young adults, could have valid treatment options such as mammalian target of rapamycin (mTOR) inhibitors with good outcomes. Furthermore, to explain possible mechanisms of action of mTOR inhibitors in this type of RCC., [Materials and Methods]: We report a case of a 44-year-old man who has been treated with everolimus for a Xp11.2 translocation/TFE3 gene-fusion RCC after 2 previous failed treatments with tyrosine kinase inhibitor. During the follow-up, we evaluated type and duration of response with everolimus., [Results]: The patient obtained a long-lasting response of disease of 25 months with everolimus without any symptom., [Conclusion]: We believe that mTOR inhibitors could be a good line option treatment to consider for this type of patients.

Zika virus (ZIKV), a recently emerged pathogen of the genus flavivirus causes Guillain-Barré syndrome and microcephaly in fetus and newborns . Until date, there are no licensed vaccine or approved drug to treat ZIKV infection. Thus, in this study, 5550 phytochemicals retrieved from various databases were subjected for molecular docking in Discovery studio V.4.0 against the ZIKV helicase protein and envelope protein domain III. In addition, in silico ADMET and Density function theory studies were performed to retain the final hit compounds. Further, four of the identified compounds (eleutheroside B, neoandrographolide, apigenin, and madecassic acid) were tested for in vitro cytotoxicity and antiviral activities against ZIKV. Except madecassic acid, the other three compounds reduced ZIKV infection at non-cytotoxic concentrations. Hence, this study encourages the screening of more phytochemicals against druggable targets of ZIKV to identify new promising drug candidates.

Introduction The objectives of this study were to describe the surgical technique of fixation of 3–4 part proximal humeral fractures with polyaxial locking plates utilising a minimally invasive approach and to evaluate the accuracy of reduction and stability of fixation. Patients and methods We retrospectively reviewed 90 patients. Fractures were classified according to the Neer classification system. Different radiological parameters were measured to assess the quality of reduction and the stability of fixation. Complications and clinical outcomes were evaluated after one year of minimum follow up. Results There were 76 women and 14 men, with a mean age of 67.4 years ± 13 (range, 29–85). There were 60 3-part and 30 4-part fractures. Frozen cancellous allograft was used in 30 cases (33.3%). All fractures progressed to union and at one year follow up, the mean Constant score was 79.6 ± 12(range, 62–100). Mean forward flexion, abduction, external rotation and internal rotation were 155°, 148°, 39° and vertebra Dorsal 8, respectively. Complications were noted in seven patients while the postoperative “head-diaphysis angle”, “greater tuberosity height” and “medial metaphysis reconstruction” were close to the anatomical parameters; no significant differences were noted at one year radiological follow up. Conclusion Reliable and stable fixation can be expected with the use of polyaxial locking plate through a minimally invasive approach for the treatment of 3–4 part proximal humeral fractures. Satisfactory functional results for this procedure can be obtained.

Flaviviruses, such as the dengue virus and the West Nile virus (WNV), are arthropod-borne viruses that represent a global health problem. The flavivirus lifecycle is intimately connected to cellular lipids. Among the lipids co-opted by flaviviruses, we have focused on SM, an important component of cellular membranes particularly enriched in the nervous system. After infection with the neurotropic WNV, mice deficient in acid sphingomyelinase (ASM), which accumulate high levels of SM in their tissues, displayed exacerbated infection. In addition, WNV multiplication was enhanced in cells from human patients with Niemann-Pick type A, a disease caused by a deficiency of ASM activity resulting in SM accumulation. Furthermore, the addition of SM to cultured cells also increased WNV infection, whereas treatment with pharmacological inhibitors of SM synthesis reduced WNV infection. Confocal microscopy analyses confirmed the association of SM with viral replication sites within infected cells. Our results unveil that SM metabolism regulates flavivirus infection in vivo and propose SM as a suitable target for antiviral design against WNV. © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Valproic acid (VPA) is a small fatty acid used for treatment of different neurologic diseases such as epilepsy, migraines or bipolar disorders. VPA modulates different processes of cell metabolism that can lead to alterations in susceptibility of several cell types to the infection of Human Immunodeficiency Virus (HIV), Epstein-Barr virus (EBV), as well as to exert an inhibitory effect on the replication of different enveloped viruses in cultured cells. Taken these data into account and the fact that HSV-1 has been involved in some neuropathies, we have characterized the effect of VPA on this herpesvirus infection of the differentiation/maturation-inducible human oligodendrocyte cell line HOG, which resulted more susceptible to VPA inhibition of virus growth after cell differentiation. In these cells, the role of VPA in virus entry was tackled. Incubation with VPA induced a slight but reproducible inhibition in the virus particles uptake mainly observed when the drug was added in the adsorption or early upon infection. In addition, transcription and expression of viral proteins were significantly downregulated in the presence of VPA. Remarkably, when the infective viral production was assessed, VPA dramatically blocked the detection of infectious HSV-1 particles. Herein, our results indicate that VPA treatment of HOG cells significantly reduces the effect of HSV-1 infection, virus entry and productivity without affecting cellular viability.

Resumen Objetivo En la rizartrosis del pulgar existe gran controversia sobre la tecnica quirurgica a elegir: trapeciectomia simple, artroplastia de reseccion-interposicion, artroplastia de reseccion-suspension, artrodesis, artroplastia de suspension-reseccion-interposicion o artroplastia con protesis. Estas 2 ultimas son las mas empleadas, sin consenso en la literatura sobre la tecnica a elegir y sin suficientes estudios comparativos. El objetivo es comparar las 2 tecnicas mas empleadas en la actualidad: artroplastia de reseccion-suspension y artroplastia con protesis. Material y metodo Presentamos un estudio prospectivo de 15 pacientes diagnosticados de rizartrosis del pulgar grados ii-iii tratados con artroplastia de reseccion-suspension (grupo 1) y 15 con protesis (grupo 2) mostrando resultados clinicos, ventajas e inconvenientes de cada una. Como variables se emplearon la escala EVA, el cuestionario DASH, la fuerza de puno y de pinza terminoterminal y terminolateral; el balance articular en aduccion-abduccion, en anteposicion-retroposicion y la oposicion. Los 2 grupos son de 2 hospitales diferentes, intervenidos por un cirujano de mano de la unidad. El tiempo de seguimiento para todos los pacientes incluidos fue de 12 meses. Resultados El EVA, DASH y fuerza de puno a los 12 meses no muestran diferencias significativas; en cuanto a la fuerza de pinza terminoterminal y terminolateral, el grupo 2 mostro los mayores valores en todos los periodos de seguimiento, con diferencias estadisticamente significativas. Conclusiones Es fundamental la seleccion del paciente y la experiencia del cirujano, dados los resultados satisfactorios de ambas tecnicas. La artroplastia con protesis se reserva para grados ii y iii , pacientes de mediana edad, buena arquitectura del trapecio y cirujanos con experiencia.

The rising interest in connecting everything to the Internet has not gone unnoticed in the energy sector. New actors that aim to remotely monitor and control home devices such as heating, ventilation and air conditioning (HVAC), light bulbs, or distributed energy resources (e.g., batteries, PV panels…) have come into play. However, transitioning from isolated often not interoperable home automation systems to open, yet secure, solutions that integrate external sources of information and cloud computing to make a more efficient use of energy, is not trivial. It requires designing and implementing hierarchical architectures and standard solutions to facilitate interoperability, one of the challenges of cross-domain smart-city applications as no standard solution has been established yet. Even though most solutions share a set of building blocks that have fostered the appearance of Internet of Things (IoT) middlewares to accelerate development, most existing energy platforms are still tailor-made for specific applications. This paper targets three audiences. First, for those interested in using or selecting an energy platform, the study carries out a comparative analysis of some of the most popular alternatives. Second, for those that are considering building new energy platforms, this paper analyzes the necessary hierarchical blocks, and the main design options and strategies. Finally, for those interested in comparing platforms, a new set of IoT levels that evaluate the adoption of IoT technologies is proposed.

Purpose: The objective of this study is to evaluate the risk of infections for herpesviruses in patients exposed to Valproic acid and derivatives (VPA) in the Spanish research database BIFAP. Methods: We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP over the period 2001 to 2015. The events of interest were those diseases caused by any of the herpesviruses known to infect humans, specifically. For each case, up to 10 controls per case matched by age, gender and calendar date were randomly selected using risk set sampling. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95%CI) for infection for herpesviruses associated to the use of VPA after adjusting for potential confounders. Results: Current use of VPA was associated with a trend towards a reduced risk of infection by herpesviruses as compared to non-users (OR 0.84; CI95% 0.7-1.0), being these differences marginally significant (p=0.053). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. Conclusions: The results of this study show a trend to a reduced risk of infection for herpesviruses in patients exposed to VPA, especially in those with treatment durations longer than 90 days. These results are consistent with in vitro studies showing that, in cultured cells, VPA inhibits the production of infectious progeny of different enveloped viruses causing relevant human and veterinary diseases, including herpesviruses. Funding Statement: Work at Centro de Biologia Molecular Severo Ochoa was supported by grants from the Spanish Ministerio de Economia y Competitividad (AGL2014-52395-C2-1-R and AGL2017-84097-C2-1- R), and by an institutional grant from the Fundacion Ramon Areces and Banco Santander Central Hispano. Work at INIA (MAM-A) was supported by grant AGL2014-56518-JIN. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The scientific committee of BIFAP granted a positive opinion to the study protocol (#08/2015). The investigators had access to only fully anonymized data, and under this condition, no specific ethics review was required according to Spanish law.

SummaryThe endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation, and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward proinflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify strategies for intervention in mitochondrial-related diseases.

© 2014 Elsevier B.V. We have analyzed the cellular pathways and metabolic adaptations that take place in primary skin fibroblasts from patients with mutations in BCS1L, a major genetic cause of mitochondrial complex III enzyme deficiency. Mutant fibroblasts exhibited low oxygen consumption rates and intracellular ATP levels, indicating that the main altered molecular event probably is a limited respiration-coupled ATP production through the OXPHOS system. Two-dimensional DIGE and MALDI-TOF/TOF mass spectrometry analyses unambiguously identified 39 proteins whose expression was significantly altered in complex III-deficient fibroblasts. Extensive statistical and cluster analyses revealed a protein profile characteristic for the BCS1L mutant fibroblasts that included alterations in energy metabolism, cell signaling and gene expression regulation, cytoskeleton formation and maintenance, and intracellular stress responses. The physiological validation of the predicted functional adaptations of human cultured fibroblasts to complex III deficiency confirmed the up-regulation of glycolytic enzyme activities and the accumulation of branched-chain among other amino acids, suggesting the activation of anaerobic glycolysis and cellular catabolic states, in particular protein catabolism, together with autophagy as adaptive responses to mitochondrial respiratory chain dysfunction and ATP deficiency. Our data point to an overall metabolic and genetic reprogramming that could contribute to explain the clinical manifestations of complex III deficiency in patients. Biological significance: Despite considerable knowledge about their genetic origins, the pathophysiological mechanisms that contribute to the clinical manifestations of mitochondrial disorders remain poorly understood. We have investigated the molecular pathways and metabolic adaptations that take place in primary skin fibroblasts from patients with mutations in the BCS1L gene, a primary cause of mitochondrial complex III enzyme deficiency. Two-dimensional DIGE together with MALDI-TOF/TOF mass spectrometry and physiological validation analyses revealed a significant metabolic and genetic reprogramming as an adaptive response to mitochondrial respiratory chain dysfunction. Our data provide information about specific protein targets that regulate the transmitochondrial functional responses to complex III deficiency, thereby opening new doors for future research., Instituto de Salud Carlos III (grant numbers PI11-00182 to C.U., PS09-01359 to M.A.M., CP11-00151 to M.M., and PI12-00933 to S.C.), by Comunidad Autónoma de Madrid

Aim The aim of the study was to evaluate the clinical and radiological results obtained in the treatment of carpal scaphoid non-union treated at the University Hospital of Valladolid using the Fisk-Fernandez technique. Materials and methods A review was performed on 43 cases of surgically treated non-union using Fisk-Fernandez technique with a minimum of 6 months follow-up. The time until surgery, previous treatment, the mechanism of injury, type of non-union, and the existence of radio-carpal arthrosis were evaluated. A subjective evaluation was performed using the “Scaphoid Score” and the DASH, plus an objective assessment with the modified Green & O’Brien, together with the measurement of the intra-scaphoid, radioulnar, scapholunate angles, and carpal height. Results The median time to healing in the series was between 16 and 24 weeks, except in 3 patients who failed to heal and required salvage surgery. There was a statistically significant variation between the preoperative and postoperative angles and carpal height measured in the X-rays. Discussion There are different osteosynthesis techniques and materials for the treatment of non-union. The evaluation of results performed using objective and subjective scales showed variable results between studies. Different techniques are aimed at preventing the progression of the disease. Conclusion The Fisk-Fernandez technique enables the deformity of the scaphoid to be corrected by wedge grafting and internal fixation with Kirschner wires or screws.

The aim of this paper is to analyze the educational practices in relation to the health of the indigenous people from Misak, in Colombia. An investigation into the educational project is being carried out from several fields using qualitative methodology, specifically the hermeneutical method, given the characteristics of the study. The framework of the educational project draws from the rights of indigenous people subject to the 1991 Constitution, to International Rights, and to the 2007 Public Policies. The specific purposes of the project are strengthening physical and evolutionary development of Misak’ children by adding psycho-objetual and neurolinguistic processes, as well as social relations based on initial own education in accordance with the community itself. Throughout this essay, we develop cultural policies and measures on ethno-education and interculturality.

This study aimed to estimate the association of cyclists' age and sex with the risk of being involved in a crash with and without adjustment for their amount of exposure. We used the distribution of the entire population and cyclists (total and non-responsible) involved in road crashes in Spain between 1993 and 2009 held by the Spanish National Institute of Statistics and the Spanish General Traffic Directorate to calculate rates of exposure and involvement in a crash. Males aged 45-49 years were used as the reference category to obtain exposure rate ratios (ERR) and unadjusted crash rate ratios (URR). We then used these values in decomposition analysis to calculate crash rate ratios adjusted for exposure (ARR). The pattern of ARR was substantially different from URR. In both sexes the highest values were observed in the youngest age groups, and the values decreased as age increased except for a slight increase in the oldest age groups. In males, a slight increase in the lowest and highest age categories was observed for crashes resulting in severe injury or death, and a decrease was observed for the youngest cyclists who were wearing a helmet. The large differences between age and sex groups in the risk of involvement in a cycling crash are strongly dependent on differences in their exposure rates. Taking exposure rates into account, cyclists younger than 30 years and older than 65 years of age had the highest risk of being involved in a crash.

Objective The collagenase from Clostridium histolyticum is a new therapeutic option, and the first pharmacological one, in the treatment of Dupuytren's disease. Material and methods A prospective study was conducted on 35 patients with Dupuytren's disease. The clinical and functional variables, as well as patient satisfaction and drug safety were evaluated. Results The functional and clinical results after its administration were good, with a rapid recovery, especially at the metacarpophalangeal (MCP) joint. The index finger contracture prior to MCP puncture was 64° and after puncture it was 4°. In the proximal interphalangeal (PIP) prior to puncture it was 83.3° and after puncture it was 15°; In the MCP/PIP prior to puncture it was 140°, and after puncture it 25°. Conclusions Collagenase from Clostridium histolyticum an alternative of treatment of Dupuytren's disease, mainly in the elderly. More research is required in order to clarify the rate of recurrence of the disease, the possible adverse reactions, and to compare the efficiency and permanence with other treatment options.

Valproic acid (VPA), a short chain fatty acid commonly used for treatment of neurological disorders, has been shown to inhibit production of infectious progeny of different enveloped viruses including the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). In this study we have investigated the mechanisms by which VPA inhibits LCMV multiplication in cultured cells. VPA reduced production of infectious LCMV progeny and virus propagation without exerting a major blockage on either viral RNA or protein synthesis, but rather affecting the cell release and specific infectivity of LCMV progeny from infected cells. Our results would support the repurposing of VPA as a candidate antiviral drug to combat arenavirus infections. © 2013 Elsevier B.V., BIO2008-0447-C03-01 and BIO2011-24351; Fundación Ramón Areces; NIH AI077719 JCT; RTA2011-00036; MAMA is the recipient of JAE-Doc fellowship from CSIC

Resumen Objetivos La descompresion del nervio mediano mediante la apertura del retinaculo flexor se considera un tratamiento satisfactorio en pacientes afectos del sindrome del tunel carpiano. No obstante, diversos factores como la edad, pueden influir en los resultados postoperatorios. Presentamos los resultados a largo plazo de la cirugia de descompresion del nervio mediano en la muneca en pacientes de edad avanzada. Metodos Se trata de un estudio prospectivo historico, a largo plazo, sobre 52 pacientes intervenidos a una edad de 65 anos o superior del sindrome del tunel carpiano. Hemos llevado a cabo una valoracion clinico-funcional (cuestionario de Levine et al.), electromiografica y dinamometrica de los pacientes estudiados, referida a un tiempo postoperatorio medio de 10 anos. Resultados Los valores del cuestionario de Levine revelaron resultados favorables en el postoperatorio, a un seguimiento medio de 10,35 anos, con una mejoria media en la escala clinica del cuestionario de 1,93 puntos (intervalo de confianza [IC] del 95%: 1,72-2,17) y en la escala funcional de 0,83 puntos (IC del 95%: 0,68-0,99). De igual modo, los valores electromiograficos presentaron una mejoria significativa respecto a sus valores preoperatorios (mejoria media de velocidad sensitiva 8,43 m/s, IC del 95%: 8,17-11,63; mejoria media de latencia motora 1,65 ms, IC del 95%: 1,24-2,25). Los datos de fuerza de presion manual no alcanzaron significacion estadistica. Conclusiones En pacientes de edad avanzada, la seccion completa del ligamento transverso del carpo permite mantener diferencias favorables en la mayoria de los parametros estudiados tras 10 anos desde la cirugia, siendo el tratamiento quirurgico una opcion recomendable.

Purpose To estimate the prevalence and importance of GSTT1, GSTM1, and CYP1B1 genotypes in renal cell carcinoma (RCC), and to identify their value as a prognostic factor. Materials and methods Cross-sectional study of a group of patients diagnosed with RCC (n = 133) and a control group (n = 208) with benign conditions and no history of tumor. Controls were selected by cumulative samples and mixed pairing. All subjects pertained to the catchment area for our hospital. Sociodemographic variables, anatomical pathology features, and presence of GSTT1, GSTM1, and CYP1B1 polymorphisms by multiplex PCR and sequencing techniques. Results There were no differences in the genotype distribution of the GSTT1 and GSTM1 genes between cases and controls. In the case of CYP1B1, the GG genotype (Ala119) was more prevalent in patients with RCC (OR = 2.08; 95% CI: 1.32–2.28) and may be implicated in 34.3% (95% CI: 16.3–52.2) of RCCs. In patients with GSTT1 deletion, TNM stages III to IV were more common (39.1%); whereas in Val432 homozygous patients in CYP1B1, Fuhrman grades 3 to 4 (54.6%) were more common. Because this was a cross-sectional study, longitudinal studies are needed in the future to confirm these data. Conclusions No relationship between GSTT1 and GSTM1 genotypes and RCC risk was observed. Homozygous subjects with Ala119 in CYP1B1 had twice the risk of RCC as homozygous for Ser119 or heterozygotes. Patients with GSTT1 deletion had tumors of more advanced stages, and those with Val432 polymorphism in CYP1B1 had tumors of higher Fuhrman grade.

Virus infection of host cells requires that entry into the cell results in efficient genome release leading to translation and replication. These initial steps revolving around the entry and genomic release processes are crucial for viral progeny generation. Despite the variety of receptors used by viruses to initiate entry, evidence from both enveloped and non-enveloped viral infections is highlighting the important role played by intracellular acidic compartments in the entry of many viruses. These compartments provide connecting nodes within the endocytic network, presenting multiple viral internalization pathways. Endosomal compartments employing an internal acidic pH can trigger molecular mechanisms leading to disassembly of viral particles, thus providing appropriate genome delivery. Accordingly, viruses have evolved to select optimal intracellular conditions for promoting efficient genome release, leading to propagation of the infectious agent. This review will address the implications of cellular compartment involvement in virus infectious processes, and the roles played by the viruses' own machinery, including pH sensing mechanisms and the methodologies applied for studying acid-dependent viral entry into host cells., Unión Europea (EU FP7 Marie Curie IAAP Action, 251420); Swiss National Science Foundation; Fundación Ramón Areces

The aim of this study was to identify the causative genetic lesion in two apparently unrelated newborns having lethal lactic acidosis, multi-organ failure and congenital malformations including interrupted aortic arch, who exhibited mild methylmalonic aciduria, combined mitochondrial respiratory chain deficiency, and marked muscle mitochondrial DNA depletion. A novel mutation in the SUCLG1 gene was identified. Phenotype severity in Succinate-CoA ligase dysfunction appears to be more correlated to the muscle mtDNA content than to the tissue distribution of the heterodimer subunits. Prominent impairment of mitochondrial respiratory chain may result in deep ravages in developmental tissues leading to multiple organ failure and malformations., This work was supported by Grants PI060547 (to M.A.M.) and PI070167 (to A.L.A. and R.G.) from Instituto de Salud Carlos III (ISCIII), Ministry of Science and Innovation (MICIN), Spain; and GEN-0269/2006 from Comunidad de Madrid (CM) (to M.A.M. and R.G.). H.R. is supported by the Grant PI060547 (ISCIII). M.J.M. is recipient of a post-doctoral fellowship from ISCIII (CD06/00031). C.U. is recipient of a “Miguel Servet” research contract from ISCIII (CI04/00011).

Objetivo Describir las caracteristicas generales de una serie de enfermos con osteomielitis vertebral hematogena (OVH) desde la perspectiva de un hospital comarcal y comparar nuestros resultados con los de otras series nacionales y extranjeras. Pacientes y metodos Analisis retrospectivo de las historias clinicas de los pacientes con OVH diagnosticados en el Hospital de Viladecans en el periodo comprendido entre 1993 y 2008. Se han incluido solo los pacientes con demostracion microbiologica de infeccion y adquiridos por via hematica. Resultados Veintiseis pacientes cumplian los criterios de inclusion, nueve mujeres y diecisiete varones, con una edad media de 61 anos (limites 36�83). La mayoria de estos tenian algun factor predisponente de base, predominando la diabetes mellitus, y estaban causados por germenes piogenos (77%). La presentacion clinica habitual fue el dolor vertebral de caracteristicas inflamatorias, observado en 23 enfermos (88,4%). La artritis septica de articulaciones perifericas fue la forma de inicio en dos pacientes (7,6%) y el abdomen agudo en un paciente. La fiebre se detecto en 22 casos (84,6%). La mortalidad fue nula, aunque las complicaciones y secuelas resultaron frecuentes y a menudo graves. Conclusiones Las caracteristicas clinicas generales de nuestra serie no difieren esencialmente de otras, tanto nacionales como extranjeras, aunque como hecho diferencial hemos detectado una incidencia predominante de etiologia estreptococica sobre la estafilococica habitual. Es resenable la nula mortalidad observada. Aunque se trata de una enfermedad infrecuente, parece que esta aumentando su incidencia, lo que unido a su potencial capacidad para ocasionar complicaciones y secuelas graves obliga a sensibilizar al colectivo medico a fin de conseguir un diagnostico mas precoz y mejorar con ello el pronostico.

Objectives To describe a series of patients with haematogenous vertebral osteomyelitis (HVO) in a primary care hospital. The results were compared with other Spanish and foreign series. Patients and methods The files of patients with HVO diagnosed in the Viladecans hospital from 1993 through 2008, were retrospectively reviewed. Only patients with microbiological demonstration of infection were included. Patients with HVO after surgical procedures were excluded. Results Twenty six patients had inclusion criteria, 9 females and 17 males, with a mean age of 61 years (range 36ndash;83). The most patients had any predisposing factor, generally diabetes mellitus. Pyogenic microorganisms were the most frequent aetiological agents (77%). Back pain was by far the most common presenting symptom (88.4%), followed by peripheral septic arthritis in two patients (7.6%), and acute abdominal pain in one. Fever was found in 22 cases (84.6%). None of our patients died, but the sequelae were non rare. Conclusion We did not find difference between our series and others. It is noteworthy that the streptococcal species represents the most frequently isolated organism, followed by Staphylococcus aureus, more common in other series. Remarkably, none of our patients died. HVO is an infrequent disease. However, evidence suggests that the incidence is increasing. Early diagnosis can avoid potential serious sequelae.

Resumen El tumor adenomatoide es el tumor paratesticular mas frecuente. Es un tumor benigno, que en la mujer se localiza fundamentalmente en el utero y trompas de Falopio, mientras que en el varon su localizacion mas frecuente es el epididimo, aunque estas lesiones tambien pueden afectar a la albuginea, cordon espermatico y, excepcionalmente, al parenquima testicular, donde solo hay publicados 5 casos, conductos eyaculadores, prostata, etc. Sus manifestaciones clinicas y datos radiologicos son, en muchas ocasiones, dificiles de diferenciar de lesiones solidas, malignas, intraparenquimatosas, lo que conlleva a realizar orquiectomias innecesarias. Presentamos un nuevo caso de tumor adenomatoide dependiente de la porcion inferior del epididimo.

Purpose To expound our experience of percutaneous screw fixation in the treatment of certain hand fractures. Materials and methods We carried out a prospective study between November 2002 and November 2006, in which 84 patients with hand fractures were treated by means of closed screw osteosynthesis. The injury was located at the base of the first metacarpal in 12 cases (14.28%) the remainder being phalangeal fractures (85.71%). All fractures were closed, 40 of them intra-articular (47.61%). The most frequent fracture type was the long oblique fracture, which was present in 68 cases (80.95%). Results Functional results obtained at the last follow-up visit (6 months) were excellent in 64 patients (76.19%), good in 15 (17.86%) and poor in 5 (5.95%). Conclusions Percutaneous screw fixation sharply reduces immobilization time permitting earlier functional recovery without causing any cosmetic defects. It is a highly useful technique for carefully selected fractures and patients.

Mutations in the assembly chaperone BCS1L constitute a major cause of mitochondrial complex III deficiency. We studied the presence of BCS1L mutations in a complex III-deficient patient with metabolic acidosis, liver failure, and tubulopathy. A previously reported mutation, p.R56X, was identified in one BCS1L allele, and two novel heterozygous mutations, g.1181A>G and g.1164C>G, were detected in the second allele. The g.1181A>G mutation generated an alternative splicing site in the BCS1L transcript, causing a 19-nucleotides deletion in its 5'UTR region. Decreased BCS1L mRNA and protein levels, and a respiratory chain complex III assembly impairment, determine a pathogenic role for the novel BCS1L mutations.

Size structure is a fundamental property in an ecosystem. We explore the potential of fractal models to describe biomass distribution within a community across a range of body-weight size. We propose a consistent method selecting a self-similar cascade generating a fractal distribution that replicates field data within a range of scales. Admissible cascades constructed from biomass distribution data are filtered out using the non-parametric Kolmogorov–Smirnov test. A specific analysis is then performed to detect the biomass spreading across a suitable size scales. This is done by computing a parameter (the balanced entropy index) that evaluates evenness in mass splitting. This method is successfully applied to replicate the distribution of fish biomass obtained from a fisheries dataset. The proposed fractal description of the community size structure of the sampled marine ecosystem may prove useful when analyzing key ecological processes which involve all individuals in a community regardless of their species.

Resumen Objetivo Exponer la experiencia de los autores en la realizacion de la tecnica de microosteosintesis percutanea con tornillos para el tratamiento de ciertas fracturas de la mano. Material y metodo Se realizo un estudio prospectivo en el periodo comprendido entre noviembre de 2002 y noviembre de 2006 en el que 84 pacientes con fracturas en la mano se trataron mediante osteosintesis a cielo cerrado con tornillos. La localizacion de la lesion fue en la base del primer metacarpiano en 12 (14,28%) ocasiones y el resto fueron fracturas de las falanges (85,71%). Todas las fracturas eran cerradas y 40 fracturas eran intraarticulares (47,61%). El tipo de fractura mas frecuente fue la oblicua larga en 68 casos (80,95%). Resultado Los resultados funcionales obtenidos tras la ultima revision (6 meses) fueron excelentes en 64 pacientes (76,19%), fueron buenos en 15 pacientes (17, 86%) y fueron malos en 5 pacientes (5,95%). Conclusiones La osteosintesis percutanea con tornillos disminuye el tiempo de inmovilizacion de la fractura al minimo, favorece una recuperacion funcional mas temprana y no deja defectos esteticos. Es una tecnica muy util en fracturas y en pacientes especialmente seleccionados.

Studies linking exposure to low levels of radiofrequencies with adverse health effects, notwithstanding their present apparent inconsistency, have contributed to a steady improvement in the quality of evaluating that exposure. In complex electromagnetic environments, with a multitude of emissions of different frequencies acting simultaneously, knowledge of the spectral content is fundamental to evaluating human exposure to non-ionizing radiation. In the present work, we quantify the most significant spectral components in the frequency band 0.5–2200 MHz in an urban area. The measurements were made with a spectrum analyzer and monopole, biconical, and log-periodic antennas. Power density levels were calculated separately for the medium wave, short wave, and frequency modulation radio broadcasting bands, and for the television and GSM , DCS , and UMTS mobile telephony bands. The measured levels were compared with the ICNIRP reference levels for exposure to multiple frequency sources for thermal effects and electrical stimulation. The results showed the criterion limiting exposure on the basis of preventing electrical stimulation of peripheral nerves and muscles to be stricter (exposure quotient 24.7 10 − 4 ) than that based on thermal considerations (exposure quotient 0.16 10 − 4 ). The bands that contribute most to the latter are short wave, with 46.2%, and mobile telephony with 32.6% of the total exposure. In a complex electromagnetic environment, knowledge of the radiofrequency spectrum is essential in order to quantify the contribution of each type of emission to the public's exposure. It is also necessary to evaluate the electrical effects as well as the thermal effects because the criterion to limit exposure on the basis of the effect of the electrical stimulation of tissues is stricter than that based on thermal effects.

Background and objective: To evaluate the factors associated with intima-media thickness (IMT) and carotid plaques in patients with familial hypercholesterolemia (FH) and to assess the evolution following 1 year of treatment. Patients and method: Subjects (n ¼ 201) diagnosed as having probable or definite FH according to the MED-PED criteria had a clinical history, physical examination, blood chemistry and lipid profile determined. Ultrasound was used to measure the IMT in both common carotid arteries and to assess the presence of plaques. The measurements were repeated in 123 of the patients after 1 year of treatment.

4 páginas, 1 figura, 1 tabla.-- et al., [Objectives]: To report on a case with a mitochondrial DNA (mtDNA) depletion syndrome. [Design and methods]: Laboratory studies were done in muscle biopsy and fibroblasts to evaluate coenzyme Q10 (CoQ10) status and quantify mitochondrial DNA. [Results]: Decreased CoQ10 values and a 78% of mtDNA depletion were detected in muscle. Mutational studies failed to reveal any pathogenic mutation in nuclear genes related with mtDNA maintenance. [Conclusions]: mtDNA depletion syndrome was associated with CoQ10 deficiency in our patient., This project was supported by grants from the Instituto de Salud Carlos III (FIS:PI04–0009, PI07-0045, PI04-0567 and PI04-1351), Diputación General de Aragón (Grupos Consolidados B33) and European Union contract LSHB-CT-2004-005151. M.D.H-M. is supported by a predoctoral fellowship FIS (FI05/00501). The CIBER de Enfermedades Raras is an initiative of the ISCIII.