Development and validation of a prognostic index (BODEXS90) for mortality in stable chronic obstructive pulmonary disease.

INTRODUCTION: Several multidimensional indices have been proposed to predict mortality in chronic obstructive pulmonary disease (COPD). The BODEX index is simple and easy to use for this purpose in all clinical settings. Only a few prognostic indices have integrated oxygenation variables, with measurement methods that are not practical for real life clinical practice in all settings. OBJECTIVES: To develop and externally validate a new prognostic index (BODEXS90) that combines the variables included in BODEX index with rest peripheral oxygen saturation measured with finger oximetry (SpO2) to predict all-cause mortality in stable COPD. METHOD: Observational, non-intervention, multicenter historic cohort study. The BODEXS90 index was developed in a derivation cohort and externally validated in a validation cohort. Calibration of the index was carried out using Hosmer-Lemeshow test. The discrimination capacity of BODEXS90 and BODEX were compared by means of receiver-operating characteristics curves. Modelling of the index was carried out by crude and adjusted Cox regression analysis. RESULTS: The derivation and validation cohorts included 787 and 1179 subjects, respectively. SpO2 predicted all cause-mortality independently of BODEX index. Discrimination capacity of BODEXS90 to predict the outcome was significantly higher than that of BODEX, particularly for more severely affected patients, both in the derivation and in the validation cohorts. CONCLUSIONS: The new index is potentially useful for designing clinical decision-making algorithms in stable COPD.

Addition of silicon to boron foliar spray in cotton plants modulates the antioxidative system attenuating boron deficiency and toxicity.

BACKGROUND: Boron (B) nutritional disorders, either deficiency or toxicity, may lead to an increase in reactive oxygen species production, causing damage to cells. Oxidative damage in leaves can be attenuated by supplying silicon (Si). The aim of this study was to assess the effect of increasing foliar B accumulation on cotton plants to determine whether adding Si to the spray solution promotes gains to correct deficiency and toxicity of this micronutrient by decreasing oxidative stress via synthetizing proline and glycine-betaine, thereby raising dry matter production. RESULTS: B deficiency or toxicity increased H2O2 and MDA leaf concentration in cotton plants. H2O2 and MDA leaf concentration declined, with quadratic adjustment, as a function of increased leaf B accumulation. Proline and glycine-betaine leaf concentration increased under B-deficiency and B-toxicity. In addition, production of these nonenzymatic antioxidant compounds was greater in plants under toxicity, in relation to deficient plants. Adding Si to the B spray solution reduced H2O2 and MDA concentration in the plants under nutrient deficiency or toxicity. Si reduced H2O2, primarily in B-deficient plants. Si also increased proline and glycine-betaine concentration, mainly in plants under B toxicity. Dry matter production of B-deficient cotton plants increased up to an application of 1.2 g L- 1 of B. The critical B level in the spray solution for deficiency and toxicity was observed at a concentration of 0.5 and 1.9 g L- 1 of B, respectively, in the presence of Si, and 0.4 and 1.9 g L- 1 of B without it. In addition, the presence of Si in the B solution raised dry matter production in all B concentrations evaluated in this study. CONCLUSION: Our findings demonstrated that adding Si to a B solution is important in the foliar spraying of cotton plants because it increases proline and glycine-betaine production and reduces H2O2 and MDA concentration, in addition to mitigating the oxidative stress in cotton plants under B deficiency or toxicity.

Rethinking prognostic factors in locally advanced or metastatic urothelial carcinoma in the immune checkpoint blockade era: a multicenter retrospective study.

BACKGROUND: Few studies have investigated the safety and efficacy of anti-PD-(L)1 antibodies in metastatic urothelial carcinoma (mUC) in daily clinical practice. Knowledge about the influence of baseline clinical and analytical factors on therapy outcomes is scarce. PATIENTS AND METHODS: We conducted a multicenter retrospective study involving 119 previously treated or untreated mUC patients under anti-PD-(L)1 therapy in a real-world scenario. The objectives of this study were to confirm the safety and efficacy of anti-PD-(L)1 monotherapy and to identify pretreatment factors influencing therapy outcomes. In addition, an independent prognostic model for overall survival (OS) was developed and internally validated. RESULTS: Median OS was 7.8 months [95% confidence interval (CI), 5.4-10.4], median progression-free survival (PFS) was 2.80 months (95% CI, 2.4-3.4), disease control rate (DCR) was 40% (95% CI, 31-49), and overall response rate (ORR) was 24% (95% CI, 15-31). Presence of peritoneal metastases was associated with poor OS [hazard ratio (HR) = 2.40, 95% CI, 1.08-5.33; P = 0.03]. Use of proton-pump inhibitors (PPI) was associated with poor OS (HR = 1.83, 95% CI, 1.11-3.02; P = 0.02) and PFS (HR = 1.94, 95% CI, 1.22-3.09; P = 0.005), and lower DCR (OR = 0.38, 95% CI, 0.17-0.89; P = 0.03) and ORR (OR = 0.18, 95% CI, 0.02-1.60; P = 0.002). The three risk category prognostic model developed included Eastern Cooperative Oncology Group performance status, PPI use, albumin level, presence of liver metastases, and presence of peritoneal metastases variables and was associated with higher risk of death (HR = 3.00, 95% CI, 1.97-4.56; P = 0.0001). CONCLUSIONS: This study confirms anti-PD-(L)1 monotherapy as a safe and effective treatment option in daily clinical practice for mUC patients. It also describes the presence of peritoneal metastases as an independent prognostic factor for OS and underlines the association between PPI use and worse therapeutic outcomes. Finally, it proposes a new easy-to-use risk-assessment model for OS prediction.

Tetraconazole alters the methionine and ergosterol biosynthesis pathways in Saccharomyces yeasts promoting changes on volatile derived compounds.

The influence of antifungal tetraconazole residues (either as an active substance or as a commercial formulation product) on the fermentative activity of Saccharomyces cerevisiae yeast was evaluated in pasteurized Garnacha red must by using laboratory-scale fermentation assays. The presence of this fungicide promoted a slight decrease in glucose consumption. Volatile fermentative-derived compounds were evaluated in deep. Statistically significant changes were found in methionol (with a mean decrease of around 24%), fatty acids (with increments ranged from 23% to 66%), and ethyl esters (with increases ranged from 23% to 145%) contents when grape musts were enriched with the commercial formulation at both contamination levels assayed. Based on protein mass fingerprinting analysis, it was possible to relate these variations on volatiles content with changes in the activity of several enzymes (Met3p, Met14p, Adh2p, Hmg1p, Erg5p, Erg6p, Erg11p, and Erg20p) involved in the secondary metabolism of yeasts.

Maintenance treatment in metastatic colorectal cancer: in search of the best strategy.

Over the last 2 decades, the standard fluoropyrimidine-based chemotherapy backbone for metastatic colorectal cancer has been complemented by the addition of novel biological agents, achieving impressive increases in 5-year survival rates. Nonetheless, these new combinations have also entailed increases in toxicity, leading to evaluation of de-escalated chemotherapy regimens and "drug holiday" periods in attempts to reduce side effects and optimise quality of life without impairing efficacy. Here, we review the current and emerging evidence for maintenance schedules with chemotherapy and targeted agents, versus continuous treatment after induction treatment, in metastatic colorectal cancer patients.

Mepanipyrim residues on pasteurized red must influence the volatile derived compounds from Saccharomyces cerevisiae metabolism.

The impact of mepanipyrim (Mep) and its corresponding commercial formulation (Mep Form) on Saccharomyces cerevisiae metabolites was assessed, separately, by using laboratory-scale wine fermentation assays on pasteurized red must. The presence of Mep did not alter the fermentation course. With regard to volatiles formed at the intracellular level by fermenting yeast cells, Mep residues affected mainly the acetate and ethyl ester biochemical pathways. In particular, the target acetates showed a notorious increment, >90%, in presence of commercial Mep Form at the higher dose assayed. The addition of Mep and Mep Form, at both tested levels, highly increased ethyl caprylate (between 42 and 63%) and ethyl caprate (between 36 and 60%) contents as the same as their respective fatty acid precursors. No important effects were observed on colour and non-volatile pyranoanthocyanins, probably due to the low anthocyanin content characteristic of pasteurized musts.

Amelanotic iris melanoma in a 7 year-old hispanic boy with subclinical globe perforation. / Melanoma amelanótico del iris en un niño hispano de 7 años con perforación del globo subclínica.

We report an unusual case of an amelanotic melanoma in a 7 year old hispanic child with subclinical globe perforation. Uveal melanoma rarely occurs in children. Young affected patients are mostly light-colored eye Caucasian adolescents. Since they are not common, these tumors are usually not recognized and misdiagnosed. Differential diagnoses and therapeutic options are outlined.

Straatsma syndrome: Satisfactory amblyopia treatment. Report of two cases. / Síndrome de Straatsma: tratamiento satisfactorio de ambliopía.Reporte de 2 casos.

CLINICAL CASES: The cases are presented on 2 female patients with Straatsma syndrome, with satisfactory treatment of amblyopia. DISCUSSION: The level of anisometropia and myelination of retinal nerve fibres were different in these two patients. However, both achieved 0.20 (logMAR) visual acuity with correction in both eyes following amblyopia treatment with ocular patching. Visual prognosis of amblyopia associated with myelination of retinal nerve fibres and anisometropia is poorer than anisometropic amblyopia without myelination. It is well known that the former is refractory to occlusive therapy. Despite having a poor prognosis, visual rehabilitation should be attempted. The two cases presented were successfully treated with eye-patching.

Validating alternative methodologies to estimate the regime of temporary rivers when flow data are unavailable.

Hydrological data for assessing the regime of temporary rivers are often non-existent or scarce. The scarcity of flow data makes impossible to characterize the hydrological regime of temporary streams and, in consequence, to select the correct periods and methods to determine their ecological status. This is why the TREHS software is being developed, in the framework of the LIFE Trivers project. It will help managers to implement adequately the European Water Framework Directive in this kind of water body. TREHS, using the methodology described in Gallart et al. (2012), defines six transient 'aquatic states', based on hydrological conditions representing different mesohabitats, for a given reach at a particular moment. Because of its qualitative nature, this approach allows using alternative methodologies to assess the regime of temporary rivers when there are no observed flow data. These methods, based on interviews and high-resolution aerial photographs, were tested for estimating the aquatic regime of temporary rivers. All the gauging stations (13) belonging to the Catalan Internal Catchments (NE Spain) with recurrent zero-flow periods were selected to validate this methodology. On the one hand, non-structured interviews were conducted with inhabitants of villages near the gauging stations. On the other hand, the historical series of available orthophotographs were examined. Flow records measured at the gauging stations were used to validate the alternative methods. Flow permanence in the reaches was estimated reasonably by the interviews and adequately by aerial photographs, when compared with the values estimated using daily flows. The degree of seasonality was assessed only roughly by the interviews. The recurrence of disconnected pools was not detected by flow records but was estimated with some divergences by the two methods. The combination of the two alternative methods allows substituting or complementing flow records, to be updated in the future through monitoring by professionals and citizens.

A biological tool to assess flow connectivity in reference temporary streams from the Mediterranean Basin.

Many streams in the Mediterranean Basin have temporary flow regimes. While timing for seasonal drought is predictable, they undergo strong inter-annual variability in flow intensity. This high hydrological variability and associated ecological responses challenge the ecological status assessment of temporary streams, particularly when setting reference conditions. This study examined the effects of flow connectivity in aquatic macroinvertebrates from seven reference temporary streams across the Mediterranean Basin where hydrological variability and flow conditions are well studied. We tested for the effect of flow cessation on two streamflow indices and on community composition, and, by performing random forest and classification tree analyses we identified important biological predictors for classifying the aquatic state either as flowing or disconnected pools. Flow cessation was critical for one of the streamflow indices studied and for community composition. Macroinvertebrate families found to be important for classifying the aquatic state were Hydrophilidae, Simuliidae, Hydropsychidae, Planorbiidae, Heptageniidae and Gerridae. For biological traits, trait categories associated to feeding habits, food, locomotion and substrate relation were the most important and provided more accurate predictions compared to taxonomy. A combination of selected metrics and associated thresholds based on the most important biological predictors (i.e. Bio-AS Tool) were proposed in order to assess the aquatic state in reference temporary streams, especially in the absence of hydrological data. Although further development is needed, the tool can be of particular interest for monitoring, restoration, and conservation purposes, representing an important step towards an adequate management of temporary rivers not only in the Mediterranean Basin but also in other regions vulnerable to the effects of climate change.

Thermodynamics of sodium dodecyl sulphate-salicylic acid based micellar systems and their potential use in fruits postharvest.

Micellar systems have excellent food applications due to their capability to solubilise a large range of hydrophilic and hydrophobic substances. In this work, the mixed micelle formation between the ionic surfactant sodium dodecyl sulphate (SDS) and the phenolic acid salicylic acid have been studied at several temperatures in aqueous solution. The critical micelle concentration and the micellization degree were determined by conductometric techniques and the experimental data used to calculate several useful thermodynamic parameters, like standard free energy, enthalpy and entropy of micelle formation. Salicylic acid helps the micellization of SDS, both by increasing the additive concentration at a constant temperature and by increasing temperature at a constant concentration of additive. The formation of micelles of SDS in the presence of salicylic acid was a thermodynamically spontaneous process, and is also entropically controlled. Salicylic acid plays the role of a stabilizer, and gives a pathway to control the three-dimensional water matrix structure. The driving force of the micellization process is provided by the hydrophobic interactions. The isostructural temperature was found to be 307.5 K for the mixed micellar system. This article explores the use of SDS-salicylic acid based micellar systems for their potential use in fruits postharvest.