T1 bladder cancer: comparison of the prognostic impact of two substaging systems on disease recurrence and progression and suggestion of a novel nomogram

Background: The T1 substaging of bladder cancer (BCa) potentially impacts disease progression. The objective of the study was to compare the prognostic accuracy of two substaging systems on the recurrence and progression of primary pathologic T1 (pT1) BCa and to test a nomogram based on pT1 substaging for predicting recurrence-free survival (RFS) and progression-free survival (PFS). Methods: The medical records of 204 patients affected by pT1 BCa were retrospectively reviewed. Substaging was defined according to the depth of lamina propria invasion in T1a-c and the extension of the lamina propria invasion to T1-microinvasive (T1m) or T1-extensive (T1e). Uni- and multivariable Cox regression models evaluated the independent variables correlated with recurrence and progression. The predictive accuracies of the two substaging systems were compared by Harrell's C index. Multivariate Cox regression models for the RFS and PFS were also depicted by a nomogram. Results: The 5-year RFS was 47.5% with a significant difference between T1c and T1a (p = 0.02) and between T1e and T1m (p < 0.001). The 5-year PFS was 75.9% with a significant difference between T1c and T1a (p = 0.011) and between T1e and T1m (p < 0.001). Model T1m-e showed a higher predictive power than T1a-c for predicting RFS and PFS. In the univariate and multivariate model subcategory T1e, the diameter, location, and number of tumors were confirmed as factors influencing recurrence and progression after adjusting for the other variables. The nomogram incorporating the T1m-e model showed a satisfactory agreement between model predictions at 5 years and actual observations. Conclusions: Substaging is significantly associated with RFS and PFS for patients affected by T1 BCa and should be included in innovative prognostic nomograms

Clinical and urodynamic findings in women affected by mixed urinary incontinence

The definition of mixed urinary incontinence (MUI) of the International Continence Society exclusively assesses patient-reported symptoms without consideration of physical and urodynamic results, what is inadequate to reliably predict the pathophysiology of the underlying pathology. We investigated and compared clinical and urodynamic findings in women with MUI and assessed predictive variables for the different MUI clinical presentations

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction

OBJECTIVE To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end

The catalytic efficiency of soybean lipoxygenase-1 is enhanced at low gravity.

Several cellular processes are modified when cells are placed under conditions of weightlessness. As yet, there is no coherent explanation for these observations, nor it is known which biomolecules might act as gravity sensors. Lipoxygenases generate leukotrienes and lipoxins from arachidonic acid, being responsible for many pharmacological and immunological effects, some of which are known to be affected by microgravity. In the course of the 28th parabolic flight campaign of the European Space Agency we measured the activity of pure soybean lipoxygenase-1 on linoleic acid, by a fibre optics spectrometer developed on purpose. It was found that microgravity reduced the apparent Michaelis-Menten constant (Km) of the enzymatic reaction to one fourth with respect to the 1 g control, whereas, the catalytic constant (k(cat)) was unaffected. Consequently, the catalytic efficiency of lipoxygenase-1 (k(cat)/Km) was approximately four-fold higher in flight than on ground. This unprecedented finding suggests that lipoxygenase-1 might be a molecular target for gravity

Anandamide uptake by synaptosomes from human, mouse and rat brain: inhibition by glutamine and glutamate

Anandamide (N-arachidonoylethanolamine, AEA) belongs to an emerging class of endogenous lipids, called "endocannabinoids". A specific AEA membrane transporter (AMT) allows the import of this lipid and its degradation by the intracellular enzyme AEA hydrolase. Here, we show that synaptosomes from human, mouse and rat brain might be an ideal ex vivo system for the study of: i) the accumulation of AEA in brain, and ii) the pharmacological properties of AMT inhibitors. Using this ex vivo system, we demonstrate for the first time that glutamine and glutamate act as non-competitive inhibitors of AEA uptake by human, mouse and rat brain AMT

Purification and characterization of a lentil seedling lipoxygenase expressed in E. coli: Implications for the mechanism of oxodiene formation by lipoxygenases

Lentil seedlings contain at least six lipoxygenase isoenzymes, which are difficult to separate by classical enzyme purification techniques. The aim of this work was to study one particular lentil seedling lipoxygenase, as previous work indicated possible interesting characteristics of this enzyme with respect to oxodiene formation. Since it proved to be difficult to obtain this enzyme in significant quantities in a pure state, we expressed it in Escherichia coli. Using an expression vector based on the T7 RNA polymerase promoter (pET11d) we achieved of a fully functional lentil seedling lipoxygenase in E. coli, which was purified to homogeneity by DEAE ion-exchange chromatography and gel-filtration. The products obtained from linoleic acid were analysed. This recombinant lipoxygenase corresponds to that found in the lower part of the epicotyl and in the hypocotyl of the lentil seedling. It produces predominantly 13-(S)-hydroperoxy-(9Z,11E)-octadecadienoic and minor amounts of 9(S)-hydroperoxy-(10E,12Z)-octadecadienoic acids, as well as significant amounts of C18-oxodienes with a regiospecificity different from hydroperoxide formation. The latter mixture was found to consist of equal amounts of 13-oxo-(9Z,11E)-octadecadienoic and 9-oxo-(10E,12Z)-octadecadienoic acids. It is concluded that (1) oxodienes formed by this lentil enzyme do not originate from a secondary conversion of hydroperoxides, but rather from a different lipoxygenase-catalysed reaction and (2) this lipoxygenase shows similarities to pea lipoxygenase G, with both representing a novel type of legume lipoxygenase