Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis.We express our deepest acknowledgement to patients and their families. The authors also acknowledge the computing resources and technical support provided by Abel Paz-Gallardo and Alfonso Pardo from Extremadura Research Centre for Advanced Technologies (CETA−CIEMAT). This work was supported FEDER cofounded MINECO grant SAF2015-66015-R, ISCIII-RETIC RD12/0036/0009, and PIE15/00076 and CB/16/00228 (to J.M. Paramio); MMF was supported by a Jose Castillejo Fellowship (CAS16/00115)

Evaluación de la cohesión de betunes modificados con polvo de neumáticos

This article reports on a study of crumb rubber-mediated improvement in bitumen cohesion, analyzed with the UCL method. UCL, a procedure developed to characterize bituminous binders, evaluates the cohesion obtained by adding a certain amount of bitumen or bituminous mastic to a standard mix aggregate. This method was chosen because it can be used to assess bitumen containing crumb rubber added by either the wet or the dry mix process. In the dry mix process crumb rubber is combined with the mix as if it were a fine aggregate; i.e., crumb rubber and binder are blended during mix manufacture, laying and compaction. In the wet mix process, the binder is blended with the crumb rubber prior to mixing with the aggregate; i.e., when added to the mix, it has already been modified. The effect of digesting this dry mixed material prior to use was also analyzed in the present study. A comparison of the dry (with and without digestion) and wet mix processes showed the latter to be more effective, particularly when the crumb rubber was blended with the binder via microscopic dispersion.El objetivo de este artículo es estudiar la influencia del polvo de neumático en la mejora de la cohesión proporcionada por la adición del polvo de neumático al betún mediante el método UCL. El método UCL es un procedimiento desarrollado para caracterizar ligantes bituminosos, basado en la evaluación de la cohesión dada por una cantidad determinada de un betún o un mástico bituminoso a unos áridos de granulometría establecida (mezcla patrón). Se ha empleado este método porque permite valorar al mismo tiempo los dos procedimientos de incorporación del polvo de neumático al betún: vía seca y vía húmeda.El procedimiento seco se lleva a cabo añadiendo el polvo de neumático a la mezcla como si fuera un filler, de modo que el polvo de neumático y el ligante se mezclan durante la fabricación, extendido y compactación de la mezcla. En el procedimiento húmedo, hay una mezcla previa del ligante con el polvo de neumático, por lo que aquél seaña de a la mezcla cuando ya ha sido modificado. También se ha estudiado la influencia de los tiempos de digestión. Se comparan los dos procedimientos, seco con y sin digestión, y húmedo. El segundo presenta una clara ventaja,especialmente cuando los ligantes son fabricados con dispersión microscópica

Case studies in physiology: Training adaptation in an elite athlete after breast cancer diagnosis.

The aim of this study was to evaluate the capacity to return to competition of a 28-yr-old female 400-m hurdle elite athlete after a diagnosis of breast cancer. The study lasted 14 mo after diagnosis. She was tested four times (T1–T4) to measure body mass (BM), body mass index (BMI), percentage of total fat mass (TFM%), total fat-free mass (TFFM%), bone mineral density (BMD), one-repetition maximum (1RM), and maximal power (MP) in bench press and half squat, maximum oxygen uptake, and 400-m dash and hurdles. T0 (baseline time) was established with values before diagnosis. BM and BMI increased from T0 to T1 (5.3% and 5.2%) and remained stable. BMD experienced no change. TFM% values decreased from T1 to T4 (3.5%). TFFM% values increased from T1 to T3 (0.9%). During T1–T2, the athlete presented a global decline from T0 in 1RMSquat, 1RMBench, MPSquat, and MPBench (32.6%, 27.2%, 37.5%, and 27.6%, respectively). Results during T3–T4 were also lower for these parameters from T0 (23.3%, 20.6%, 23.4%, and 11%). During T1–T2, the V̇o2max declined compared with T0 (1.8% and 6.4%), showing a small increase at T3 (+1%) and reaching the lowest level at T4 (9%). During T1–T2, the time record of 400-m dash (8.3%) and hurdles (7.4%) increased. However, a slight improvement was found at T3 (1.3% and 0.6%, respectively). The results of this case study reflect that exercise training improved body composition, maintained BMD and TFFM, but could not completely reverse the worsening of the cardiorespiratory, muscle strength and power, and running performance levels.pre-print325 K

Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis

Bienestar mental y optimismo laboral en empleados turísticos de una región de Perú

The objective was to determine the relationship between mental well-being and labor optimism in tourist collaborators in the Junín region. The paradigm was positivist-quantitative, basic type, relational level, non-experimental-transectional design. Observational and inductive-deductive method. The probabilistic-stratified sample consisted of 384 dependents. The results showed that there is a direct and significant correlation between positive mental health and optimism, with a bilateral significance level of less than 1%, as well as a Kendall Tau b correlation strength of 0.445. It is concluded that the greater the mental well-being, the greater the labor optimism.El objetivo fue determinar la relación entre bienestar mental y optimismo laboral en colaboradores turísticos de la región Junín. El paradigma fue positivista-cuantitativo, tipo básico, nivel relacional, diseño no experimental. Método observacional e inductivo-deductivo. La muestra probabilística-estratificada fue de 384 dependientes. Los resultados mostraron que existe correlación directa y significativa entre salud mental positiva y optimismo, con un nivel de significancia bilateral inferior al 1 %, así como una fuerza de correlación Tau b de Kendall de 0.445. Se concluye que, a mayor bienestar mental, mayor optimismo laboral

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

Harnessing the potential of ligninolytic enzymes for lignocellulosic biomass pretreatment

Abundant lignocellulosic biomass from various industries provides a great potential feedstock for the production of value-added products such as biofuel, animal feed, and paper pulping. However, low yield of sugar obtained from lignocellulosic hydrolysate is usually due to the presence of lignin that acts as a protective barrier for cellulose and thus restricts the accessibility of the enzyme to work on the cellulosic component. This review focuses on the significance of biological pretreatment specifically using ligninolytic enzymes as an alternative method apart from the conventional physical and chemical pretreatment. Different modes of biological pretreatment are discussed in this paper which is based on (i) fungal pretreatment where fungi mycelia colonise and directly attack the substrate by releasing ligninolytic enzymes and (ii) enzymatic pretreatment using ligninolytic enzymes to counter the drawbacks of fungal pretreatment. This review also discusses the important factors of biological pretreatment using ligninolytic enzymes such as nature of the lignocellulosic biomass, pH, temperature, presence of mediator, oxygen, and surfactant during the biodelignification process