coupling of temperature and strain in thermal softening of a stainless steel at low and high strain rates

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Elastic Modulus Profiles in the Cross Sections of Drying Alkyd Coating Films: Modelling and Experiments

The temporal development of the modulus of elasticity and its profile were studied in water-borne alkyd coatings during the drying process of the coating films. Values of the Young’s moduli of elasticity of free coating films were measured using tensile tests. Since the elastic modulus is related to cross-link density, the values of the moduli give information on the advancement of the drying process. A mathematical model was developed to predict the degree of effective cross-linking and the mechanical behaviour of the drying coating films with different thicknesses. This model is based on trends observed by confocal Raman microspectroscopy, which exhibit the profile of the consumption of double bonds and thus can be used to monitor the development of cross-link density as a function of depth from the film surface. The average values of the Young’s measured moduli were successfully described by the numerical model as a function of drying time

Editorial

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Hydrogen sulphide is involved in testosterone vascular effect

BACKGROUND: Testosterone (T) induces a rapid relaxation in vascular tissues of different species due to a nongenomic effect of this steroid on vessels. Different mechanisms have been proposed to explain T-induced vasodilatation but the effective mechanism(s) and the mediators involved are still a matter of debate. OBJECTIVES: We have evaluated if H(2)S pathway is involved in T vascular effects. DESIGN AND SETTING: Male Wistar rats were sacrificed and thoracic aorta was rapidly dissected and cleaned from fat and connective tissue. Rings of 2-3 mm length were cut and placed in organ baths filled with oxygenated Krebs solution at 37 degrees C and mounted to isometric force transducers. H(2)S determination was performed on thoracic aortic rings incubated with T or vehicle and in presence of inhibitors. H2S concentration was calculated against a calibration curve of NaHS (3-250 microM). Results were expressed as nmoles/mg protein. MEASUREMENTS: Vascular reactivity was evaluated by using isometric transducers. H(2)S determination was performed by using a cystathionine beta-synthetase (CBS) and cystathionine gamma lyase (CSE) activity assay. CSE and CBS protein levels were assessed by Western blot analysis. Statistical analysis was performed by using two-way ANOVA and unpaired Student's t-test where appropriate. RESULTS: T significantly increased conversion of L-cysteine to H(2)S. This effect was significantly reduced by PGG and BCA, two specific inhibitors of CSE. T (10 nM-10 microM) induced a concentration-dependent vasodilatation of rat aortic rings in vitro that was significantly and concentration-dependent inhibited by PGG, BCA, and glybenclamide. Incubation of aorta with T up to 1 h did not change CBS/CSE expression, suggesting that T modulates enzymatic activity. CONCLUSIONS: Here we demonstrate that T vasodilator effect involves H(2)S, a novel gaseous mediator. T modulates H(2)S levels by increasing the enzymatic conversion of L-cysteine to H(2)S

Mystery(n) Phenotypic Presentation in Europeans: Report of Three Further Novel Missense RNF213 Variants Leading to Severe Syndromic Forms of Moyamoya Angiopathy and Literature Review

Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy in some cases occurring in children. Incidence is higher in East Asia, where the heterozygous p.Arg4810Lys variant in RNF213 (Mysterin) represents the major susceptibility factor. Rare variants in RNF213 have also been found in European MMA patients with incomplete penetrance and are today a recognized susceptibility factor for other cardiovascular disorders, from extracerebral artery stenosis to hypertension. By whole exome sequencing, we identified three rare and previously unreported missense variants of RNF213 in three children with early onset of bilateral MMA, and subsequently extended clinical and radiological investigations to their carrier relatives. Substitutions all involved highly conserved residues clustered in the C-terminal region of RNF213, mainly in the E3 ligase domain. Probands showed a de novo occurring variant, p.Phe4120Leu (family A), a maternally inherited heterozygous variant, p.Ser4118Cys (family B), and a novel heterozygous variant, p.Glu4867Lys, inherited from the mother, in whom it occurred de novo (family C). Patients from families A and C experienced transient hypertransaminasemia and stenosis of extracerebral arteries. Bilateral MMA was present in the proband's carrier grandfather from family B. The proband from family C and her carrier mother both exhibited annular figurate erythema. Our data confirm that rare heterozygous variants in RNF213 cause MMA in Europeans as well as in East Asian populations, suggesting that substitutions close to positions 4118-4122 and 4867 of RNF213 could lead to a syndromic form of MMA showing elevated aminotransferases and extracerebral vascular involvement, with the possible association of peculiar skin manifestations

Daidzein plus isolase associated with zinc improves clinical symptoms and quality of life in patients with LUTS due to benign prostatic hyperplasia: Results from a phase I-II study

Objective: In the last years there is a growing interest in nutraceutical substances that seems able to improve clinical symptoms in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). In this paper, we evaluated both efficacy and safety of a combination of daidzein with isolase and zinc in patients with LUTS due to BPH. Materials and methods: In a phase I-II study clinical trial we enrolled patients with clinical and instrumental diagnosis of LUTS associated to BPH that received a six-month treatment with a combination of daidzein with isolase and zinc (1 tablet/day). Clinical, laboratory and instrumental analyses were carried out at the time of admission (T0) and 6 months after the ending of the treatment (T1). The Italian version of International Prostatic Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and Quality of Well-Being (QoL) questionnaires were used. The development of adverse drug reactions (ADRs) and drug interactions (DDIs) were recorded using the Naranjo scale and drug interaction probability scale. Student's t test and Anova test were used for statistical analysis, and the threshold of statistical significance was set at P < 0.05. Results: We enrolled 71 patients, 62 (87.3%) completed the follow-up and we documented a significant differences between T0 and T1 in terms of IPSS [21.5 ± 1.2 vs 16.2 ± 1.5; (-4.8); p < 0.001], Cmax [9.7 ± 3.7 vs 15.3 ± 2.5; (+5.6); p < 0.001] and QoL [0.56 ± 0.15 vs 0.84 ± 0.19; (+0.28); p < 0.001]. In contrast, no significant difference were recorded in terms of IIEF-5 [p = 0.50] and PSA [p = 0.67]. Finally, we did not record any significant ADRs or DDIs during the study. Conclusions: In this study, we documented that a combination of daidzein with isolase and zinc, reduces the clinical symptoms of LUTS and improves the quality of life in patients with BPH, without the development of ADRs or DDIs

Urothelium muscarinic activation phosphorylates CBS Ser227 via cGMP/PKG pathway causing human bladder relaxation through H 2 S production

The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders

Human Cystathionine-β-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium

Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-β-synthase. Here, we demonstrate that human cystathionine-β-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP) but not dibutyryl-cyclic-adenosine monophosphate (d-cAMP) causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-β-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-β-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-β-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-β-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-β-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity

Erectile dysfunction and mobile phone applications: Quality, content and adherence to European Association guidelines on male sexual dysfunction

Introduction: Nowadays numerous mobile health applications (MHA) have been developed to assist and simplify the life of patients affected by erectile dysfunction (ED), however the scientific quality and the adherence to guidelines are not yet addressed and solved. Materials and methods: On 17 January 2022, we conducted a search in the Apple App Store and Google Play Store.We reviewed all mobile apps from iTunes App Store and Google Play Store for ED and evaluated different aspects as well as their usage in screening, prevention, management, and their adherence to EAU guidelines. Results: A total of 18 apps were reviewed. All apps are geared towards the patient and provide information about diagnoses and treatment of ED. Conclusions: MHA represent an integral part of patients' lives, and apps providing services for male sexual dysfunction are constantly increasing. Despite this the overall quality is still low. Although many of these devices are useful in ED, the problems of scientific validation, content, and quality are not yet solved. Further work is needed to improve the quality of apps and developing new accessible, user designed, and high-quality apps