Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m²) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥ 6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.     

Models of the interconnection of pumps to supply water to branched networks

The basic concepts from a hydraulic and mathematical point of view were introduced to describe the operation of a hydraulic branched network of water distribution. Moreover, each one of the elements (simples and complex) of the system was identified. Classic hydraulic equations were inputted to apply them to branched networks and obtain a standard solution. A set of linear and non-linear equations, through the Newton–Raphson method with the jacobian matrix were required to solve the branched network that interconnects two kinds of very different pumps: a volute type centrifugal pump and another one is submersible pump, both of them installed in a deep well. The system is a branched network with two nodes and five pipe lines, to adequately supply two pressure irrigation systems: a central pivot and a semi-portable sprinkler, where the pumps are located in different places and heights. The solution was obtained by solving a system of two linear equations and three non-linear, simultaneously.     

Effect of sodium selenite addition and sponge dough fermentation on selenomethionine generation during production of yeast-leavened breads

The effect of sodium selenite addition and fermentation times on production of selenomethionine (SeM) during sponge bread production was evaluated. Doughs were supplemented with sodium selenite (Na₂SeO₃) and fermented with yeast, avoiding addition of sulfur salts. The effect of Na₂SeO₃ on yeast activity was evaluated using a pressurometer. Results showed that there were not statistical differences (p < 0.05) in CO₂ production and dough pH at all the sodium selenite concentrations tested. HPLC-fluorescence data showed that SeM production was higher with the increase of fermentation times, while less significant effects were observed due to changes in Na₂SeO₃ concentration. Two slices of Se-enriched bread can provide about 200 μg SeM, the dose recommended to prevent cancer and oxidative stress. The physical features (water absorption, bread weight, bread volume, color, density, oven spring, etc.) and organoleptic evaluations for the enriched loaves were evaluated. In all these parameters, the experimental enriched breads had practically identical attributes compared to the control. The breads rich in SeM have potential to be used as functional foods because this amino acid is synthesized into higher quantities of glutathione peroxidase, an enzyme considered as one of the most protective mechanisms against oxidative stress and preventive of cancer and chronic diseases.     

Field indicators of leaf nutritive value for perennial ryegrass and tall fescue pastures under different growing and management conditions

Field indicators of forage nutritive value could help farmers with rapid management decisions to optimize timing and intensity of grazing and meet objectives regarding animal nutrition. The objective of this research was to evaluate the likely relationships among leaf blade nutritive value, herbage mass and leaf stage of pasture regrowth under different growing seasons and residual sward heights. Experiments were performed on perennial ryegrass (Lolium perenne L.) and tall fescue (Festuca arundinacea Schreb.) pastures during spring and summer of 2016. In both pastures, three residual sward height treatments (3, 6 and 12 cm) were imposed on plots arranged in a split plot design, replicated in three blocks. Sward plots were harvested 5–6 times at intervals spaced 7–10 days apart to measure herbage mass, plant morphology, neutral detergent fibre (NDF), and the 24-hr in vitro digestibility of NDF (NDFD) and dry matter (DMD) of leaf blades. Pastures showed strong (R²: .62 to .70), but variable, negative relationships between NDFD and herbage mass that varied with the rate at which pasture grew in each season of experimentation. Although there was a consistent NDFD decline as leaf stage of regrowth progressed (R²: .75 to .97), the NDFD also decreased as residual sward height increased, most notably in tall fescue. Additionally, findings indicate that the greater leaf length plasticity of tall fescue compared to residual sward heights may offer opportunities to manage both post- and pre-grazing targets to achieve tall fescue forages with a similar high nutritive value as perennial ryegrass. However, the evaluation of this hypothesis at the farm level and its impacts on animal intake and performance warrants further careful investigations.     

Plastic deformation of MgGeO3 post-perovskite at lower mantle pressures

Polycrystalline MgGeO3 post-perovskite was plastically deformed in the diamond anvil cell between 104 and 130 gigapascals confining pressure and ambient temperature. In contrast with phenomenological considerations suggesting (010) as a slip plane, lattice planes near (100) became aligned perpendicular to the compression direction, suggesting that slip on (100) or (110) dominated plastic deformation. With the assumption that silicate post-perovskite behaves similarly at lower mantle conditions, a numerical model of seismic anisotropy in the D' region implies a maximum contribution of post-perovskite to shear wave splitting of 3.7% with an oblique polarization.     

Horizontal transmission of Beauveria bassiana spores using infected males and inoculation device: impact on survival and fecundity of Ceratitis capitata (Diptera: Tephritidae)

Phytoparasitica - The mode of transmission of fungus spores (horizontal transmission or assisted auto-dissemination) directly influences the effectiveness of a fungal pathogen when used as a...     

Protoplast technology for the breeding of top-fruit trees (Prunus, Pyrus, Malus, Rubus) and woody ornamentals

Summary Until recently, temperate fruit trees and woody ornamentals have been regarded as recalcitrant to biotechnological breeding approaches based on protoplasts. This however should no longer be the case, as procedures are now available, not only for the regeneration of complete plants from protoplasts of various tissues of such species, but also for the exploitation of protoplast technology for their genetic manipulation. This paper will examine the recent advances and state of the art in this domain, with particular attention to the use of protoplast technology as a novel tool in the breeding of rosaceous top-fruit tree species and woody ornamentals. Problems and their solutions within the context of regenerating plants from isolated protoplasts of stone (Prunus spp.), pome (Pyrus spp., Malus spp.) and small (Rubus spp.) fruits, and of several shrubby ornamental genotypes (Lonicera spp., Weigela spp., Forsythia spp., Cotoneaster spp.) will be addressed. Interspecific (Prunus spinosa + Prunus cerasifera) and intergeneric (Forsythia spp. + Syringa spp.) somatic hybridization within this group of species, as well as the use of protoplasts for host/pathogen interaction studies (Pyrus/Erwinia amylovora) will also be discussed.     

High antinutrient levels and bruchid resistance of cowpea (Vigna unguiculata) seeds

Summary Seeds of some cowpea varieties, characterized by different degrees of storage pest resistance, were analyzed for inhibitors of the following enzymes: porcine amylase, Bacillus amylase, bovine chymotrypsin and trypsin. A broad variation was observed among samples for all tested inhibitors. Submitting the experimental data to the principal component analysis it has been observed that resistant lines are characterized by high levels of both antitryptic and antiamylasic activity. Moreover a high activity of a single inhibitor class is typical of the bruchid susceptible lines. Hence, breeding for high contents of these protein inhibitors could be an effective way of obtaining lines that are naturally resistant to storage pest attack. The limit of this breeding strategy seems to be the difficulty to reduce the antiamylasic activity before eating.     

Broccoli ( Brassica oleracea var. italica) sprouts and extracts rich in glucosinolates and isothiocyanates affect cholesterol metabolism and genes involved in lipid homeostasis in hamsters

This study investigated the effects of broccoli sprouts (BS) on sterol and lipid homeostasis in Syrian hamsters with dietary-induced hypercholesterolemia. Treatments included freeze-dried BS containing 2 or 20 μmol of glucoraphanine (BSX, BS10X), glucoraphanine-rich BS extract (GRE), sulforaphane-rich BS extract (SFE), and simvastatin. Each experimental diet was offered to eight animals (male and female) for 7 weeks. Hepatic cholesterol was reduced by BS10X and SFE treatments in all animals. This correlated with a down-regulation of gene expression of sterol regulatory element-binding proteins (SREBP-1 and -2) and fatty acid synthase (FAS) caused by GRE and SFE diets. BS10X caused changes in gene expression in a gender-specific manner; additionally, it increased coprostanol excretion in females. With the same concentration of glucoraphanin, consumption of broccoli sprouts (BS10X) had more marked effects on cholesterol homeostasis than GRE; this finding reinforces the importance of the matrix effects on the bioactivity of functional ingredients.