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There are few publications related to postoperative morbidity in hepatic hydatidosis and these have mixed results. The aim of this study was to determine risk and protective factors of postoperative morbidity in patients operated on for hepatic hydatidosis. A comprehensive review was made of the evidence, based on systematic reviews, clinical analyses and observational studies, obtained from the Trip Database, BVS, SciELO, Cochrane Central Register of Controlled Trials, WoS, MEDLINE, EMBASE, SCOPUS, EBSCOhost, IBECS, ePORTUGUESe, LILACS and WHOLIS. 1,087 related articles were identified; 69 fulfilled the selection criteria (2 systematic reviews, 3 clinical trials and 64 observational studies). Age, history of previous surgery for hepatic hydatidosis, location in the hepatic center, existence of biliary communications and evolutionary complications of the cyst were identified as risk factors, and radical surgical techniques as protective factors. Risk and protective factors were identified; however, the studies are few and the quality moderate to low.

Resumen El objetivo de la investigación fue describir el contexto histórico cultural de Forrahue, Pucatrihue y Neltume y su influencia en las condiciones de vida de las personas mayores que pertenecen a organizaciones sociales de personas mayores. Estudio cualitativo, interpretativo y crítico realizado en el segundo trimestre del año 2017. El estudio se realizó en tres localidades rurales del sur de Chile, seleccionadas según características sociodemográficas de los territorios y viabilidad de la investigación. Participaron tres organizaciones sociales de personas mayores de 60 años, contactadas por informantes claves, trabajadores de dispositivos de atención primaria de las localidades. Se realizaron tres grupos de discusión y entrevistas en profundidad a un total de 18 personas mayores, principalmente mujeres, integrantes de organizaciones sociales. Para procesar los datos, se usó análisis de contenido. El estudio muestra el rol positivo de la asociatividad y participación social para la mantención de estados de salud y la mitigación de condiciones de vida que determinan vulnerabilidad: pobreza, aislamiento y deterioro producto de la edad. Evidencia la necesidad de integrar la participación social como una estrategia sanitaria, desde el reconocimiento de formas naturales de convivencia y no estructuradas desde agentes sanitarios. Se presenta evidencia sobre el valor del sentido de pertenencia territorial en la edad avanzada y de la actividad con sentido compartido y cotidiano. Abstract The aim of the research presented was to describe the historical and cultural context of Forrahue, Pucatrihue and Neltume and their influence on the living conditions of older people belonging to social organisations of older people. Qualitative, interpretative and critical study carried out in the second quarter of 2017. The study was carried out in three rural localities in southern Chile, selected according to the socio-demographic characteristics of the territories and the viability of the research. Three social organizations of people over 60 years of age participated, contacted by key informants, workers of primary care devices in the localities. Three discussion groups and in-depth interviews were conducted with a total of 18 older people, mostly women, members of social organizations. Content analysis was used for the analysis. The study shows the positive role of association and social participation in maintaining health conditions and mitigating living conditions that determine vulnerability: poverty, isolation and deterioration due to age. Evidence of the need to integrate social participation as a health strategy, from the recognition of natural forms of coexistence and unstructured from health agents. Evidence is presented on the value of the sense of territorial belonging in advanced age and of activity with shared, everyday meaning.

The CRISPR/Cas9 system is a novel genetic tool which allows the precise manipulation of virtually any genomic sequence. In this protocol, we use a specific CRISPR/Cas9 system for the manipulation of Ashbya gossypii. The filamentous fungus A. gossypii is currently used for the industrial production of riboflavin (vitamina B2). In addition, A. gossypii produces other high-value compounds such as folic acid, nucleosides and biolipids. A large molecular toolbox is available for the genomic manipulation of this fungus including gene targeting methods, rapid assembly of heterologous expression modules and, recently, a one-vector CRISPR/Cas9 editing system adapted for A. gossypii that allows marker-free engineering strategies to be implemented. The CRISPR/Cas9 system comprises an RNA guided DNA endonuclease (Cas9) and a guide RNA (gRNA), which is complementary to the genomic target region. The Cas9 nuclease requires a 5'-NGG-3' trinucleotide, called protospacer adjacent motif (PAM), to generate a double-strand break (DSB) in the genomic target, which can be repaired with a synthetic mutagenic donor DNA (dDNA) by homologous recombination (HR), thus introducing a specific designed mutation. The CRISPR/Cas9 system adapted for A. gossypii largely facilitates the genomic edition of this industrial fungus.

The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%-10%. The genetic basis is unknown in the majority of families although around 10%-13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes. Panel sequencing was performed of 35 genes associated with hereditary cancer in 43 PDAC cases from families with an apparent hereditary pancreatic cancer syndrome. Pathogenic variants were identified in 19% (5/26) of PDAC cases from pure FPC families in the genes MLH1, CDKN2A, POLQ and FANCM. Low frequency potentially pathogenic VUS were also identified in 35% (9/26) of PDAC cases from FPC families in the genes FANCC, MLH1, PMS2, CFTR, APC and MUTYH. Furthermore, an important proportion of PDAC cases harboured more than one pathogenic, likely pathogenic or potentially pathogenic VUS, highlighting the multigene phenotype of FPC. The genetic basis of familial or hereditary pancreatic cancer can be explained in 21% of families by previously described hereditary cancer genes. Low frequency variants in other DNA repair genes are also present in 35% of families which may contribute to the risk of pancreatic cancer development. This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund ''A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer: RTICC (RD12/0036/0073) and La Asociación Española contra el Cáncer: AECC (Grupos Coordinados Estables 2016). This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund "A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Tematica de investigacion cooperativa en cancer: RTICC (RD12/0036/0073) and La Asociacion Espanola contra el Cancer: AECC (Grupos Coordinados Estables 2016). Sí

Esta obra recoge algunas experiencias de formacion en recreacion de promotores ludicos del pais y presenta un profundo analisis en torno a la pertinencia de la recreacion en diversos contextos en los que la relacion con los ninos exige agentes de cambio creativos y reflexivos. En ese sentido, se revisan aspectos de la ensenanza de orden teorico y empirico postulados por autores de diferentes tendencias de la recreacion y el ocio que facilitan la construccion de propuestas o modelos de educacion de la recreacion. A su vez, se expone puntos de vista concretos acerca de la produccion de conocimiento y, por tanto, de realizacion practica del ocio en el contexto latinoamericano y, en particular, colombiano. Finalmente, este libro propone opciones concretas para el desarrollo practico del ocio en torno a la lectura recreativa y se analiza criticamente la idea convencional acerca del acoplamiento de objetos tecnicos en el cuerpo humano.

Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder. However, the combination of the insidious onset of LD and the lack of awareness on these rare diseases among medical personnel results in undesirable diagnostic delays, with unchecked disease progression, appearance of complications and a worsened prognosis. We tested the usefulness of a next‐generation sequencing‐based gene panel for quick, early detection of LD among cases of idiopathic splenomegaly and/or thrombocytopenia, two of the earliest clinical signs observed in most LD. Our 73‐gene panel interrogated 28 genes for LD, 1 biomarker and 44 genes underlying non‐LD differential diagnoses. Among 38 unrelated patients, we elucidated eight cases (21%), five with LD (GM1 gangliosidosis, Sanfilippo disease A and B, Niemann‐Pick disease B, Gaucher disease) and three with non‐LD conditions. Interestingly, we identified three LD patients harboring pathogenic mutations in two LD genes each, which may result in unusual disease presentations and impact treatment. Turnaround time for panel screening and genetic validation was 1 month. Our results underline the usefulness of resequencing gene panels for quick and cost‐effective screening of LDs and disorders sharing with them early clinical signs.

The authors wish to make the following corrections to this paper [...]

espanolEsta investigacion explora y describe como personas mayores, residentes en Rininahue (Chile), viven el envejecimiento, perciben su salud y enfermedad y se familiarizaron con la medicina hegemonica. Da cuenta de c.mo influyen sus creencias religiosas y cosmovision; como se asocia a un estilo de vida, al trabajo, el autosustento y la vida dificil. Mediante entrevistas en profundidad a seis personas mayores, analizadas desde la historia oral, se distingue enfermedad de padecer; vinculado a formas de vida propias de la ruralidad y a una estructura de valores que posiciona la autonomia, la libertad y la ocupacion como una forma de alcanzar el bienestar, asociado al territorio y a una matriz economico-social particular. Concluye sobre la relevancia de analizar las necesidades de los seres humanos en funcion de sus particularidades historico-territoriales y sociales, por sobre la estandarizacion de la politica publica. EnglishThis study explores and describes how elderly people living in the Rininahue area in the south of Chile live ageing, perceive their health and illness and were acquainted with hegemonic medicine. It also reports how religious beliefs and a particular cosmovision influence this, and how this is associated to a lifestyle, the work, the self-sustenance and the hard life. Using in-depth interviews to six elderly people, analyzed from an oral history methodology, illness and suffering are distinguished. This is related to forms of life that belong in rurality and a structure of values that positions autonomy, freedom and occupation as ways to achieve wellbeing, associated to the territory and to a particular economic and social matrix. The paper concludes about the relevance of analyzing the needs of human beings in the light of their own historical-territorial and social particularities, over standardizing of public policy.

Solitary fibrous tumors (SFTs) are a rare type of soft tissue sarcoma of unpredictable clinical behavior. Some clinicopathologic characteristics have also been related to patient outcome. This study is a retrospective review of 30 patients. We analyzed the clinical course and pathological factors to predict recurrence. The mean age was 55.9 years. Forty-five percent were located in the thoracic region. The mean tumor size was 10 cm (max24). Thirty-three percent had a relapse and 20 % have died. Median time to relapse was 7.18 (1–13) years. Median overall survival (OS) was 15.5 years (0–32). On histopathologic analysis, 6 % percent had >4 mitoses, 23 % had necroses, and 36 % had atypia/pleomorphism. Forty-three percent had tumor size >10 cm. Forty-six percent had at least one characteristic of malignancy. None of this data could predict clinical behavior by itself. SFT can be an aggressive disease and relapses can occur several years from diagnosis. We did not find any clinicopathologic factors that could predict the tumor behavior accurately. Nevertheless, it should be consider that we included different tumor locations and the sample size is small.

Esta investigación centra su interés en el estudio de la economía familiar, específicamente en los residentes del fraccionamiento Residencias del municipio de Mexicali Baja California, el estudio del ahorro y la generación de presupuestos en los gastos de las familias mexicalenses es considerado un punto de suma importancia para el control del ingreso familiar. La economía actual ha limitado el tiempo dedicado por los jefes de familia a las labores como lo es la preparación de alimentos en casa, lo que provoca recurrir a la adquisición de alimentos preparados. Esta problemática nos conlleva a preguntar si ¿la economía familiar se ve disminuida por el gasto hormiga en el consumo de alimentos preparados fuera de casa? La respuesta se orienta a afirmar que el impacto en el deterioro del ingreso familiar si se ve disminuido por el gasto hormiga en la compra de alimentos preparados, un resultado significativo en este sentido fue que el 57.5% de los residentes encuestados gasta más de lo contemplado en comida rápida, lo cual desequilibra el ingreso familiar.

Los cambios asociados al envejecimiento y las posibilidades de satisfacción de las necesidades que de ello se derivan, hacen que en Chile los espacios comunitarios de atención y nuevas estrategias de intervención se transformen en una posibilidad para la mantención y la recuperación de la salud de las personas mayores. El objetivo fue identificar el valor terapéutico del “juego” en personas mayores, como un aporte con fines terapéuticos, especialmente en contextos de intervención en comunidad con esta población. El presente artículo muestra los resultados de una investigación-acción-participativa con 12 personas mayores de 60 años, en siete sesiones, durante el año 2013 en la comuna de Valdivia, Región de Los Ríos (Chile). Se realizó un taller experiencial abierto, grupo de discusión y aplicación del test de Jugueteo. Se muestra el efecto de la vinculación comunitaria para la construcción de un significado positivo de la actividad lúdica. Se describen conductas de las personas mayores sobre la base de indicadores que evidencian el impacto en el desempeño de actividades terapéuticas. La sistematización de la investigación-acción-participativa muestra el significado atribuido a la actividad lúdica, por sobre la atribución a la recreación, la resignificación de espacios lúdicos dentro de lo cotidiano y comunitario, que permite pensarlo como estrategia terapéutica innovadora.

Summary The filamentous fungus Ashbya gossypii is currently used for the industrial production of vitamin B2. Furthermore, the ability of A. gossypii to grow using low‐cost substrates together with the inexpensive downstream processing makes this fungus an attractive biotechnological chassis. Indeed, the production in A. gossypii of other high‐added value compounds such as folic acid, nucleosides and biolipids has been described. Hence, the development of new methods to expand the molecular toolkit for A. gossypii genomic manipulation constitutes an important issue for the biotechnology of this fungus. In this work, we present a one‐vector CRISPR/Cas9 system for genomic engineering of A. gossypii. We demonstrate the efficiency of the system as a marker‐less approach for nucleotide deletions and substitutions both with visible and invisible phenotypes. Particularly, the system has been validated for three types of genomic editions: gene inactivation, the genomic erasure of loxP scars and the introduction of point mutations. We anticipate that the use of the CRISPR/Cas9 system for A. gossypii will largely contribute to facilitate the genomic manipulations of this industrial fungus in a marker‐less manner.

The perioperative nutritional status of patients undergoing cardiac surgery influences outcomes; therefore nutritional support is essential for these patients. Owing to the lack of solid evidence, no protocols have been established for the nutritional management of this specific population, and most of the recommendations are based on other critically ill populations. In this review of the main studies performed in this population, the importance of preoperative evaluation of nutritional status, the management of nutritional support immediately after cardiac surgery, the influence of nutrition on outcomes, and the importance of nutrition after hospital discharge are discussed. In addition, the possible influence of glycemic control and pharmaconutrition in the outcomes of these patients are described briefly.

The aim of this work was to characterize the antibiotic susceptibility and genetic diversity of 41 Streptococcus gallolyticus subsp. gallolyticus isolates: 18 isolates obtained from animals and 23 human clinical isolates. Antibiotic susceptibility was determined by the semiautomatic Wider system and genetic diversity by pulsed-field gel electrophoresis (PFGE) with SmaI. Animal isolates grouped separately in the PFGE analysis, but no statistical differences in antimicrobial resistance were found between the two groups. The LMG 17956 sequence type 28 (ST28) strain recovered from the feces of a calf exhibited high levels of resistance to vancomycin and teicoplanin (MIC, ≥256 mg/liter). Its glycopeptide resistance mechanism was characterized by Southern blot hybridization and a primer-walking strategy, and finally its genome, determined by whole-genome sequencing, was compared with four closely related S. gallolyticus subsp. gallolyticus genomes. Hybridization experiments demonstrated that a Tn 1546 -like element was integrated into the bacterial chromosome. In agreement with this finding, whole-genome sequencing confirmed a partial deletion of the vanY-vanZ region and partial duplication of the vanH gene. The comparative genomic analyses revealed that the LMG 17956 ST28 strain had acquired an unusually high number of transposable elements and had experienced extensive chromosomal rearrangements, as well as gene gain and loss events. In conclusion, S. gallolyticus subsp. gallolyticus isolates from animals seem to belong to lineages separate from those infecting humans. In addition, we report a glycopeptide-resistant isolate from a calf carrying a Tn 1546 -like element integrated into its chromosome.

BackgroundThe introduction of ‘smoke-free laws’ has reduced the population’s exposure to second-hand smoke (SHS), although SHS is still an issue in homes and other public places. Children are vulnerable to its health effects, and their greatest exposure occurs at home.ObjectivesTo assess airborne nicotine concentration of the living room and children’s bedroom of homes with children under 13 years of age, and to analyse factors associated with these levels.MethodsWe conducted a cross-sectional study in Barcelona in 2015–2016, selecting a convenience sample from families with at least one child under 13 years of age. The sample comprised 50 families with smokers and 50 without. We measured airborne nicotine concentrations in the living room and children’s bedroom, and, using a questionnaire administered to the parents, collected information about smoking habits at home.ResultsHomes without smokers showed nicotine concentrations below the limit of detection (3), while those with at least one smoker showed 0.16 µg/m3 in the living room and 0.12 µg/m3 in the bedroom. When smoking was allowed inside home, these values increased to 1.04 and 0.48 µg/m3, respectively. Moreover, nicotine concentrations in both rooms were strongly correlated (r=0.89), and higher nicotine levels were associated with the number of cigarettes smoked in the living room, smoking rules, the number of smokers living at home and tobacco smell.ConclusionsHomes with smokers present SHS in the living room and in the children’s bedroom. Therefore, programmes focused on reducing children’s SHS exposure are urgently needed.

Biotic indices developed to assess the ecological status of coastal waters according to the European Water Framework Directive (WFD) often show discrepancies when they are applied in transitional environments. Although several indices have been widely used in transitional waters throughout Europe, there is still a lack of knowledge about their suitability assessing ecological status. We evaluated the performance of most common used biotic indices and community parameters (e.g. Multivariate AZTI's Marine Biotic Index (M-AMBI), BENTIX, Benthic Opportunistic Polychaetes Amphipods index (BOPA), diversity indices, species richness, abundance) that have been proposed in the scope of WFD, using data of macroinvertebrate community coming from a special case of transitional water body, the highly stratified Ebro estuary. Additionally, we tested their ability to respond to the main pressures affecting the Ebro estuary, the hydrological alteration due to regulation and the pollution pressure due to nutrient enrichment. Estimation of hydrological alteration was based on flow historical data (period from 1913 to 1963), that we assumed as 'hydrological reference conditions' for Ebro estuary. Pollution pressure was estimated by means of PCA analysis including organic and nutrient enrichment related variables, expressed as a synthetic index by PCA factor scores extraction. All the community parameters were able to detect changes in macrofauna composition along the estuarine gradients and were able to differentiate between the impoverished stations and the healthier ones. Regarding indices, the ratings were contradictory and only M-AMBI classified the stations in the correct way. Strong significant correlations were found between indices and metrics and the calculated pressures; nevertheless, these correlations showed a paradoxical result, since increasing hydrological alteration benefited the macrofauna, achieving great complexity. Other identified limitations of biotic indices were the opposite classifications, overestimation of ecological status and low resolution ability. We conclude that for transitional water ecosystems, where each water body has particular characteristics, is difficult the use of 'common biological' assessment tools as the results of this study, among others (more details in discussion section), have demonstrated. Nevertheless, M-AMBI seemed to work in the correct way, so further investigation about its use for transitional waters is necessary. The development of new strategies such as the use of historical data, the use of metrics as a complement for the assessment could be a reliable alternative.

This study aimed at investigating the effects of a commercially available energy drink on shooting precision, jump performance and endurance capacity in Young basketball players. Sixteen young basketball players (first division of a junior national league; 14.9 ± 0.8 years; 73.4 ± 12.4 kg; 182.3 ± 6.5 cm) volunteered to participate in the research. They ingested either (a) an energy drink that contained 3 mg of caffeine per kg of body weight or (b) a placebo energy drink with the same appearance and taste. After 60 min for caffeine absorption, they performed free throw shooting and three-point shooting tests. After that, participants performed a maximal countermovement jump (CMJ), a repeated maximal jumps test for 15 s (RJ-15), and the Yo–Yo intermittent recovery test level 1 (Yo–Yo IR1). Urine samples were obtained before and 30 min after testing. In comparison to the placebo, the ingestion of the caffeinated energy drink did not affect precision during the free throws (Caffeine = 70.7 ± 11.8 % vs placebo = 70.3 ± 11.0 %; P = 0.45), the three-point shooting test (39.9 ± 11.8 vs 38.1 ± 12.8 %; P = 0.33) or the distance covered in the Yo–Yo IR1 (2,000 ± 706 vs 1,925 ± 702 m; P = 0.19). However, the energy drink significantly increased jump height during the CMJ (38.3 ± 4.4 vs 37.5 ± 4.4 cm; P\0.05) mean jump height during the RJ-15 (30.2 ± 3.6 vs 28.8 ± 3.4 cm; P\0.05) and the excretion of urinary caffeine (1.2 ± 0.7 vs 0.1 ± 0.1 lg/mL; P\0.05). The intake of a caffeine-containing energy drink (3 mg/kg body weight) increased jump performance although it did not affect basketball shooting precision.

INTRODUCTION: The 2016 update of the World Health Organization (WHO) classification criteria for Polycythemia Vera (PV) included a decrease of the hemoglobin threshold. This modification increases exponentially the individuals with potential PV. International groups have proposed diagnostic algorithms for the screening of individuals with potential PV. However, these algorithms are not based on the prevalence of JAK2V617F in this population, and to our concern has not been prospectively validated. Our aim is to develop and validate an algorithm based on previously reported prevalence of JAK2V617F in individuals with potential PV in our environment. METHODS: This study was designed in two phases: a first phase for the development of the algorithm and a second phase for the validation of the algorithm. Phase 1: from previous data collected from our group of JAK2 V617F prevalence in individuals with erythrocytosis according to WHO criteria we performed an area under the curve (ROC) analysis with optimal cutoff point in order to maximize sensibility and specificity of the collected variables. The thresholds for platelets and neutrophils were selected for being clinically relevant and with an AUC >0.8. With these two variables and their optimal cutoff point, a sequential 2-step-algorithm was designed (figure 1). Phase 2: for the validation of the algorithm, hemograms from outpatient individuals were selected, and the "2-step-algorithm" was applied. Therefore, if samples met the criteria for step 1 (hemoglobin > 16.5 g/dl for men or 16 g/dl for women or hematocrit >49 % for men or 48 % for women) then, the step 2 was applied (platelets > 248x103/ml or neutrophils>5.98x103/ml). Finally, all samples that passed the 2-step-algorithm, were tested for JAK2 V617F. With the chosen samples a JAK2 V617F qualitative PCR with a sensibility of at least >0.1% was performed. The positive results were validated and quantified in our reference laboratory, and those with an allele burden >1% were considered positive. RESULTS: A total of 15298 hemograms were initially selected. Of those, 1595 (10.4%) met the erythrocytosis criterion (step 1). 581 (36%) of these met the step 2 criteria and the JAK2 V617F PCR was performed in 501 samples. A total of 7 positive cases (1.4%) were found, none of which was previously diagnosed of myeloproliferative neoplasm. The median of hemoglobin and hematocrit was 16.3 g/dl and 50.3% respectively. Of the selected samples, 2 of them met the platelet criterion, 4 of them the neutrophils criterion and 1 of them met both. After reviewing clinical records, 43.8% of them were found to have cardiovascular events history history: 1 patient had atherosclerosis of the lower limbs, 1 had acute coronary syndrome and 1 had an ischemic stroke. Characteristics of JAK2V617F individuals are detailed in table 1. Comparing to step 1, the addition of step 2 increases the efficiency of the algorithm 1.75 times. In order to know the prevalence of JAK2 V617F clonal hematopoiesis in our environment, 300 unselected samples were tested. We found 1 positive result. However, after reviewing clinical records, this sample was found to belong to a patient with known myeloproliferative neoplasm. Thus, JAK2 V617F prevalence in our environment was considered CONCLUSION: This "2-step-algorithm" is a reproducible and validated tool for the screening of JAK2 V617F myeloproliferative neoplasms. Disclosures Piris-Villaespesa: Novartis: Honoraria, Other: Advisory Boards. Martinez-Lopez:Incyte: Honoraria, Other: Advisory boards; Novartis: Honoraria, Other: Advisory boards; BMS: Honoraria, Other: Advisory boards; VIVIA Biotech: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria; Amgen: Honoraria, Other: Non-Financial Support ; Janssen: Honoraria, Other: Advisory boards and Non-Financial Support ; Celgene: Honoraria, Other: Advisory boards and Non-Financial Support .

The purpose of this study was to investigate the effectiveness of a caffeine-containing energy drink in enhancing rugby players' physical performance during a simulated match. A second purpose was to determine the urinary caffeine excretion derived from the energy drink intake. In a randomized and counterbalanced order, 26 elite rugby players (mean ± SD for age and body mass, 25 ± 2 y and 93 ± 15 kg) played 2 simulated rugby games (2 × 30 min) 60 min after ingesting (i) 3 mg of caffeine per kilogram of body mass in the form of an energy drink (Fure, ProEnergetics) or (ii) the same drink without caffeine (placebo). During the matches, the individual running distance and the instantaneous speed were measured, and the number of running actions above 20 km·h−1(i.e., sprints) were determined, using global positioning system devices. The number of impacts above 5 g during the matches was determined by accelerometry. The ingestion of the energy drink, compared with the placebo, increased the total distance covered during the match (4749 ± 589 vs 5139 ± 475 m, p < 0.05), the running distance covered at more than 20 km·h−1(184 ± 38 vs 208 ± 38 m, p < 0.05), and the number of sprints (10 ± 7 vs 12 ± 7, p < 0.05). The ingestion of the energy drink also resulted in a greater overall number of impacts (481 ± 352 vs 641 ± 366, p < 0.05) and a higher postexercise urine caffeine concentration (0.1 ± 0.1 vs 2.4 ± 0.9 μg·mL−1, p < 0.05). The use of an energy drink with a caffeine dose equivalent to 3 mg·kg−1considerably enhanced the movement patterns of rugby players during a simulated match.

The aim of this study was to determine the effects of a caffeine-containing energy drink on physical performance during a rugby sevens competition. A second purpose was to investigate the post-competition urinary caffeine concentration derived from the energy drink intake. On two non-consecutive days of a friendly tournament, 16 women from the Spanish National rugby sevens Team (mean age and body mass = 23 ± 2 years and 66 ± 7 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink (Fure®, ProEnergetics) or the same drink without caffeine (placebo). After 60 min for caffeine absorption, participants performed a 15-s maximal jump test, a 6 × 30 m sprint test, and then played three rugby sevens games against another national team. Individual running pace and instantaneous speed during the games were assessed using global positioning satellite (GPS) devices. Urine samples were obtained pre and post-competition. In comparison to the placebo, the ingestion of the energy drink increased muscle power output during the jump series (23.5 ± 10.1 vs. 25.6 ± 11.8 kW, P = 0.05), running pace during the games (87.5 ± 8.3 vs. 95.4 ± 12.7 m/min, P

A complete analytical protocol for the determination of 25 doping-related peptidic drugs and 3 metabolites in urine was developed by means of accurate-mass quadrupole time-of-flight (Q-TOF) LC-MS analysis following solid-phase extraction (SPE) on microplates and conventional SPE pre-treatment for initial testing and confirmation, respectively. These substances included growth hormone releasing factors, gonadotropin releasing factors and anti-diuretic hormones, with molecular weights ranging from 540 to 1320Da. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. Weak cation exchange SPE followed by C18 HPLC chromatography and accurate mass detection provided the required sensitivity and selectivity for all the target peptides under study. 2mg SPE on 96-well microplates can be used in combination with full scan MS detection for the initial testing, thus providing a fast, cost-effective and high-throughput protocol for the processing of a large batch of samples simultaneously. On the other hand, extraction on 30mg SPE cartridges and subsequent target MS/MS determination was the protocol of choice for confirmatory purposes. The methodology was validated in terms of selectivity, recovery, matrix effect, precision, sensitivity (limit of detection, LOD), cross contamination, carryover, robustness and stability. Recoveries ranged from 6 to 70% (microplates) and 17-95% (cartridges), with LODs from 0.1 to 1ng/mL. The suitability of the method was assessed by analyzing different spiked or excreted urines containing some of the target substances.

Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumours, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole exome sequencing of the endometrioid and undifferentiated components as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: a) hypermutated tumours with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); c) high copy number alterations (copy-number high) tumours group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%) ; and d) low copy number alterations (copy-number low) tumours with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumours. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumours, which may have prognostic value.

Multimesh nylon gillnets were set in three Ebro Delta (North-East of Spain) lagoons to determine mesh selectivity for the inhabiting fish community. Each gillnet consisted on a series of twelve panels of different mesh size (ranging from 5.0 to 55.0 mm bar length) randomly distributed. The SELECT method (Share Each Length’s Catch Total) was used to estimate retention curves through five models: normal location, normal scale, gamma, lognormal and inverse Gaussian. Each model was fitted twice, under the assumptions of equal and proportional to mesh size fishing effort, but no differences were found between approaches. A possible situation of overfishing in the lagoons, where artisanal fisheries are carried out with a low surveillance effort, was assessed using a vulnerable species inhabiting these brackish waters as case study: the sand smelt, Atherina boyeri . The minimum size for its fishery has not been established, thus remaining under an uncontrolled exploitation situation. Therefore, a Minimum Landing Size (MLS) is proposed based on sexual maturity data. The importance of establishing an adequate MLS and regulate mesh sizes in order to respect natural maturation length is discussed, as well as, the proposal of other measures to improve A. boyeri fishery management.

Matrix effects (ion suppression/enhancement) are a well-observed phenomenon in analyses of biological matrices by high-performance liquid chromatography-mass spectrometry (LC-MS). However, few simple solutions for detecting and minimizing these adverse effects have been described so far in multianalyte analysis, especially in the field of doping control. This study describes an exhaustive characterization of matrix effects in one hundred urine samples fortified with 41 analytes (glucocorticoids and diuretics). It introduces a novel marker to identify samples in which the reliability of the results is compromised because of acute ion suppression. This new strategy strengthens the rigor of the analysis for screening purposes. Once the matrix effect is identified, a selective sample preparation is introduced to minimize the adverse ion suppression effect. That selective extraction together with the use of a deuterated internal standard permits enhancing the ruggedness of the estimation of glucocorticoid concentration in urine.

Laboratories devoted to the public health field have to face the analysis of a large number of organic contaminants/residues in many different types of samples. Analytical techniques applied in this field are normally focused on quantification of a limited number of analytes. At present, most of these techniques are based on gas chromatography (GC) or liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS). Using these techniques only analyte-specific information is acquired, and many other compounds that might be present in the samples would be ignored. In this paper, we explore the potential of time-of-flight (TOF) MS hyphenated to GC or LC to provide additional information, highly useful in this field. Thus, all positives reported by standard reference targeted LC-MS/MS methods were unequivocally confirmed by LC-QTOF MS. Only 61% of positives reported by targeted GC-MS/MS could be confirmed by GC-TOF MS, which was due to its lower sensitivity as nonconfirmations corresponded to analytes that were present at very low concentrations. In addition, the use of TOF MS allowed searching for additional compounds in large-scope screening methodologies. In this way, different contaminants/residues not included in either LC or GC tandem MS analyses were detected. This was the case of the insecticide thiacloprid, the plant growth regulator paclobutrazol, the fungicide prochloraz, or the UV filter benzophenone, among others. Finally, elucidation of unknowns was another of the possibilities offered by TOF MS thanks to the accurate-mass full-acquisition data available when using this technique.

The ergogenic effect of caffeine is well-established, but the extent of its consumption in sport is unknown at the present. The use of caffeine was considered &ldquo, prohibited&rdquo, until 2004, but this stimulant was moved from the List of Prohibited Substances to the Monitoring Program of the World Anti-Doping Agency to control its use by monitoring urinary caffeine concentration after competition. However, there is no updated information about the change in the use of caffeine as the result of its inclusion in the Monitoring Program. The aim of this study was to describe the changes in urine caffeine concentration from 2004 to 2015. A total of 7488 urine samples obtained in official competitions held in Spain and corresponding to athletes competing in Olympic sports (2788 in 2004, 2543 in 2008, and 2157 in 2015) were analyzed for urine caffeine concentration. The percentage of samples with detectable caffeine (i.e., &gt, 0.1 &mu, g/mL) increased from ~70.1%, in 2004&ndash, 2008 to 75.7% in 2015. The median urine caffeine concentration in 2015 (0.85 &mu, g/mL) was higher when compared to the median value obtained in 2004 (0.70 &mu, g/mL, p &lt, 0.05) and in 2008 (0.70 &mu, 0.05). The urine caffeine concentration significantly increased from 2004 to 2015 in aquatics, athletics, boxing, judo, football, weightlifting, and rowing (p &lt, 0.05). However, the sports with the highest urine caffeine concentration in 2015 were cycling, athletics, and rowing. In summary, the concentration of caffeine in the urine samples obtained after competition in Olympic sports in Spain increased from 2004 to 2015, particularly in some disciplines. These data indicate that the use of caffeine has slightly increased since its removal from the list of banned substances, but urine caffeine concentrations suggest that the use of caffeine is moderate in most sport specialties. Athletes of individual sports or athletes of sports with an aerobic-like nature are more prone to using caffeine in competition.

Introduction: The diagnostic criteria for polycythemia vera (PV) has recently been updated by the World Health Organization (WHO). The criterion for erythrocytosis has been modified downwards: hemoglobin (hb)> 16.5 g/dL or hematocrit (hto)> 49% in men and hb> 16 g/dL or hto> 48% in women. This reduction increases the potential number of patients that would be test for JAK2 V617F mutation if PV is suspected. The V617F mutation in the JAK2 gene is present in 95% of cases of PV. It is estimated that the prevalence of this mutation in the general population is around 0.2%. Our aims are to determine the prevalence of JAK2 V617F in individuals with erythrocytosis according to WHO2016 criteria and to find prognostic factors that could help to identify patients with PV. Methods: We prospectively studied all hemograms performed in our laboratory during 7 nonconsecutive days. Variables studied were hb, hto, leukocytes, neutrophils, platelets, MCV, MCH, MCHC and RDW. JAK2 V617F mutation was studied in all males that had hb> 16.5 g/dl or hto> 49% or females that had hb> 16 g/dl or hto> 48%. JAK2 V617F mutation was studied by PCR assay in which an amplification control fragment and the JAK2 mutant allele were simultaneously amplified. All positive samples were confirmed by quantitative real-time PCR in a reference laboratory. Positive results were considered when the JAK2 V617F allele ratio was ≥ 0.7. The variables collected were correlated with the result of the JAK2 test in a univariate way. The T-Student test was used for the quantitative variables and the Chi-square test for the categorical variables. For the cell count variables, the Mann-Whitney U test was used. Results: A total of 15366 HG were analyzed. 1271 (8.3%) met the inclusion criteria for erythrocytosis. JAK2 V617F was performed on 1001 samples (270 samples were not suitable for the PCR assay due to low quality). Twelve samples (1.2%) were positive for JAK2 V617F mutation. However, 5 samples were excluded due to a known diagnosis of myeloproliferative neoplasm. Therefore, finally prevalence of JAK2 V617 mutation in 996 patients that met WHO erythrocytosis criteria was 0.8% (8/996). Medians for all parameter studied for each group are shown in table 1. In order to find out parameters that could increase the incidence probabilities to identify patients with JAK2 V617F we performed an univariate analysis of the variables included, according to JAK2 mutational status. We found that patients with JAK2 V617F had higher levels of leukocytes, neutrophils, platelets and RDW than patients with negative JAK2 (p Conclusion: The prevalence of JAK2 V617F mutation in subjects with elevated Hb or hto according to WHO2016 criteria is increased with respect to that of the general population. Among this group of subjects, those with JAK2 V617F show significantly different levels of leukocytes, neutrophils, platelets, MCV, CMH and RDW. Interestingly, neutrophils, platelets and RDW show high sensitivity and specificity. Therefore, it is necessary to explore combinations of these parameters and their optimal cut-off points to elaborate efficient strategies for an early diagnostic approach. Disclosures Martinez Lopez: Bristol Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau. García Gutiérrez:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Incyte: Honoraria, Research Funding.

Smoke-free legislation in indoor public places has concentrated smokers in the areas outside building entrances or other outdoor areas. This study assessed the drift of second-hand smoke between outdoor and indoor areas of cafes and restaurants in Barcelona, Spain, and characterized the exposure on outdoor terraces. Using a cross-sectional design, we monitored vapor-phase nicotine in indoor areas and outside entrances simultaneously (n=47), and on some outdoor terraces (n=51). We computed the median nicotine concentration and inter quartile range (IQR) to describe the data and performed multivariate analysis to describe nicotine concentration and its determinants. The overall median nicotine concentration indoors was 0.65 mu g/m(3) (IQR: 029-1.17 mu g/m(3)), with significant differences based on the number of smokers at the entrance (p=0.039). At outside entrances, the overall median nicotine concentration was 0.41 mu g/m(3) (IQR: 0.21-1.17 mu g/m(3)). The nicotine concentrations indoors and at the corresponding outside entrances were not significantly different, and the multivariate analysis confirmed the relationship between these variables. On terraces, the overall median nicotine concentration was 0.54 mu g/m(3) (IQR: 025-1.14 mu g/m(3)), but it increased to 0.60 mu g/m(3) when a tobacco smell was perceived, 0.72 mu g/m(3) on closed terraces, 124 mu g/m(3) when there were > 6 smokers, and 1.24 mu g/m(3) when someone smoked > 20 min. Multivariate analysis confirmed the outdoor terrace area, the season, the type of enclosure, and the number of smokers as the most relevant variables explaining nicotine concentration (R-2=0.396). These findings show that second-hand smoke exposure exists in indoor areas due to smokers smoking at the outside entrances. In addition, exposure may occur on outdoor terraces when smokers are present and the terrace is enclosed to some extent. Thus, the current Spanish law does not fully protect nonsmokers from second-hand smoke and supports extending regulation to some outdoor areas. (C) 2016 Elsevier Inc All rights reserved.

Purified lipase from Mucor miehei (MML) has been covalently immobilized on different epoxy resins (standard hydrophobic epoxy resins, epoxy-ethylenediamine, epoxy-iminodiacetic acid, epoxy-copper chelates) and adsorbed via interfacial activation on octadecyl-Sepabeads support (fully coated with very hydrophobic octadecyl groups). These immobilized enzyme preparations were used under slightly different conditions (temperature ranging from 4 to 25 °C and pH values from 5 to 7) in the hydrolytic resolution of ( R , S )-2-butyroyl-2-phenylacetic acid. Different catalytic properties (activity, specificity, enantioselectivity) were found depending on the particular support used. For example, the epoxy-iminodiacetic acid-Sepabeads gave the most active preparation at pH 7 while, at pH 5, the ethylenediamine-Sepabeads was superior. More interestingly, the enantiomeric ratio ( E ) also depends strongly on the immobilized preparation and the conditions employed. Thus, the octadecyl-MML preparation was the only immobilized enzyme derivative which exhibited enantioselectivity towards R isomer (with E values ranging from 5 at 4 °C and pH 7 to 1.2 at pH 5 and 25 °C). The other immobilized preparations, in contrast, were S selective. Immobilization on iminodiacetic acid-Sepabeads afforded the catalyst with the highest enantioselectivity ( E =59 under optimum conditions).

Caffeine is an ergogenic aid widely used before and during prolonged exercise. Due to its prolonged biological half-life caffeine effects could remain after exercise. We aimed to investigate the metabolic, respiratory, and cardiovascular postexercise responses to preexercise graded caffeine ingestion. Twelve aerobically trained subjects (mean VO2max = 54 ± 7 ml · min−1 · kg−1) cycled for 60-min at 75% VO2max after ingesting placebo (0 mg of caffeine per kg of body weight) or 0.5, 1.5, 3.0 and 4.5 mg · kg−1 on five occasions. During the 3 hr postexercise, heart rate, blood pressure, glucose, lactate, and fatty acids were analyzed. None of these variables were statistically affected by preexercise caffeine ingestion between 0.5 and 4.5 mg · kg−1. However, ingestion of 4.5 mg · kg−1 of caffeine raised postexercise energy expenditure 15% above placebo (233 ± 58 vs. 202 ± 49 kcal/3 hr; p < .05). Ventilation and tidal volume were elevated after the 4.5 mg·kg−1 caffeine dose above placebo (9.2 ± 2.5 L · min−1 and 0.67 ± 0.29 L · breath−1 vs. 7.8 ± 1.5 L · min−1 and 0.56 ± 0.20 L · breath−1, respectively; p < .05). Ventilation correlated with tidal volume (r = .45; p < .05) and energy expenditure (r = .72; p < .05). In summary, preexercise ingestion of ergogenic caffeine doses do not alter postexercise cardiovascular responses. However, ingestion of 4.5 mg · kg−1 of caffeine raises 3-hr postexercise energy expenditure (i.e., 31 kcal) likely through increased energy cost of ventilation.

Octadecyl–Sepabeads (Mitsubishi Chemical Corporation) was used to immobilize the lipases from Candida antarctica (fraction B), from Mucor miehei and from Candida rugosa via interfacial adsorption. The activity and stability properties of the derivatives obtained using this strategy by “stabilization of the open structure of the lipase” were compared to other more conventional immobilized derivatives (e.g. those obtained by multipoint covalent attachment) where the lipases are likely to be immobilized exhibiting its closed structure. Lipases adsorbed on hydrophobic supports exhibited a clear hyper-activation compared to the soluble enzyme or other types of derivatives. Their specific activities were greatly improved after immobilization (M. miehei lipase derivative was even 20 times more active than the soluble enzyme). Furthermore, lipases adsorbed on hydrophobic supports were very stable against heat and organic solvents inactivation. For example, C. antarctica B lipase octadecyl derivatives preserved 100% of the activity after 200 h of incubation at pH 7 and 50 °C. In addition, these derivatives remained also fully active after a very long incubation (200 h) in 50% dioxane at pH 7 and 25 °C. In spite of being immobilized by simple physical adsorption these lipase derivatives were more stable than multipoint covalently immobilized derivatives and much more stable than their respective soluble enzyme. It seems that the “open structure” of lipases, adsorbed on hydrophobic supports, is much more active and much more stable than the corresponding “closed” structure even when the closed structure is undergoing a very intense multipoint covalent attachment.

Las desigualdades en salud constituyen una prioridad creciente, en la medida que éstas se han hecho más evidentes y las estrategias implementadas, han fracasado. El resultado de la Comisión de Determinantes Sociales de la Salud impulsada por la OMS, estimuló la reflexión y entregó un avance en la interpretación conceptual; no obstante, este no es más que la ratificación institucional del tema, que en América Latina lleva décadas presente, con la explicación desde la medicina social y la salud colectiva. Críticas a las sugerencias hechas por la Comisión, giran sobre la falta de una aproximación concreta y territorial a las políticas sociales. Así, el objetivo del artículo es pasar revista al documento de la OMS sobre Determinantes sociales de la salud, analizar las políticas sociales de Chile, para finalmente, someter a cuestión el rol de la Terapia ocupacional, que como disciplina del área de la salud, ha de contribuir en el desarrollo de estrategias que cumplan con lo esgrimido por el organismo internacional. El propósito es tensionar la reflexión sobre un eje insoslayable para el cumplimiento de lo planteado por la Comisión: la formación de una masa crítica sobre la cuestión social y política de los agentes de salud.

In the United States today there are over 1,000 graduate programs offering master's degrees in management and operations research. Many of these programs, including those offered at 1st-tier schools, are based on models developed in the 1960s and 1970s. Although they continue to attract a greater number of students each year, industry professionals have been critical of such programs. In this article, the authors discuss the development and characteristics of graduate programs in management and operations research, critically assess them, and offer recommendations for integrating these 2 disciplines so that their continuous improvement and revision can meet both student and business needs.