The subchronic effects of 3,4-methylendioxymethamphetamine on oxidative stress in rat brain

The aim of the present study was to evaluate the subchronic effects of 3,4-methylenedioxymethamphetamine on several oxidative stress markers: index of lipid peroxidation (ILP), superoxide dismutase (SOD) activity, superoxide radical (O2.-) levels, and reduced glutathione (GSH) levels in the frontal cortex, striatum and hippocampus of the rat. The study included 64 male Wistar rats (200-250 g). The animals were treated per os with of 5, 10, or 20 mg/kg of 3,4-methylenedioxymethamphetamine (MDMA) every day for 15 days. The subchronic administration of MDMA resulted in an increase in ILP, SOD and O2.-, and a decrease in GSH, from which we conclude that oxidative stress was induced in rat brain

Fractional Flow Reserve Method in Cardiac Catheterization Laboratory without Cardiosurgical Backup: Initial Experiences

Background: Coronary artery disease is the most common cause of death in a modern world. This dictates the development a network of Catheterization laboratories without cardiosurgical capabilities.Aim: We postulate that the most valuable tool in the decision process on myocardial revascularization is fractional flow reserve (FFR), especially when we deal with borderline coronary lesions.Material and Methods: A total of 72 patients with 94 intermediate coronary stenosis (30%-70% diameter reduction) were included in this study. We tested FFR and angiography based decision model on myocardial revascularization.Results:  Mean FFR value on left anterior descending coronary artery (LAD) was lower than in others two arteries (p=0.017). FFR after percutaneous coronary intervention (PCI) was significantly better (p<0.0001). The decision for PCI predominates before FFR diagnostics, but after FFR the decision is quite opposite. There is a weak negative correlation between FFR and diameter of stenosis assessed by angiography (r= - 0.245 p=0.038) and positive correlation between diameter of stenosis assessed by angiography and by quantitative coronary angiography (QCA) (r=0.406 p<0.0005).Conclusion:  Our results strongly suggest that FFR is necessary tool in centers without possibilities of heart team onsite consultation and that prevents numerous unnecessary PCI

Vintage venoms: proteomic and pharmacological stability of snake venoms stored for up to eight decades

For over a century, venom samples from wild snakes have been collected and stored around the world. However, the quality of storage conditions for "vintage" venoms has rarely been assessed. The goal of this study was to determine whether such historical venom samples are still biochemically and pharmacologically viable for research purposes, or if new sample efforts are needed. In total, 52 samples spanning 5 genera and 13 species with regional variants of some species (e.g., 14 different populations of Notechis scutatus) were analysed by a combined proteomic and pharmacological approach to determine protein structural stability and bioactivity. When venoms were not exposed to air during storage, the proteomic results were virtually indistinguishable from that of fresh venom and bioactivity was equivalent or only slightly reduced. By contrast, a sample of Acanthophis antarcticus venom that was exposed to air (due to a loss of integrity of the rubber stopper) suffered significant degradation as evidenced by the proteomics profile. Interestingly, the neurotoxicity of this sample was nearly the same as fresh venom, indicating that degradation may have occurred in the free N- or C-terminus chains of the proteins, rather than at the tips of loops where the functional residues are located. These results suggest that these and other vintage venom collections may be of continuing value in toxin research. This is particularly important as many snake species worldwide are declining due to habitat destruction or modification. For some venoms (such as N. scutatus from Babel Island, Flinders Island, King Island and St. Francis Island) these were the first analyses ever conducted and these vintage samples may represent the only venom ever collected from these unique island forms of tiger snakes. Such vintage venoms may therefore represent the last remaining stocks of some local populations and thus are precious resources. These venoms also have significant historical value as the Oxyuranus venoms analysed include samples from the first coastal taipan (Oxyuranus scutellatus) collected for antivenom production (the snake that killed the collector Kevin Budden), as well as samples from the first Oxyuranus microlepidotus specimen collected after the species' rediscovery in 1976. These results demonstrate that with proper storage techniques, venom samples can retain structural and pharmacological stability. This article is part of a Special Issue entitled: Proteomics of non-model organisms. Biological significance: •These results show that with proper storage venoms are useful for decades.•These results have direct implications for the use of rare venoms

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Radiological and material characterization of high volume fly ash concrete

The main goal of research presented in this paper was the material and radiological characterization of high volume fly ash concrete (HVFAC) in terms of determination of natural radionuclide content and radon emanation and exhalation coefficients. All concrete samples were made with a fly ash content between 50% and 70% of the total amount of cementitious materials from one coal burning power plant in Serbia. Physical (fresh and hardened concrete density) and mechanical properties (compressive strength, splitting tensile strength and modulus of elasticity) of concrete were tested. The radionuclide content (Ra-226, Th-232 and (40)k) and radon massic exhalation of HVFAC samples were determined using gamma spectrometry. Determination of massic exhalation rates of HVFAC and its components using radon accumulation chamber techniques combined with a radon monitor was performed. The results show a beneficial effect of pozzolanic activity since the increase in fly ash content resulted in an increase in compressive strength of HVFAC by approximately 20% for the same mass of cement used in the mixtures. On the basis of the obtained radionuclide content of concrete components the I -indices of different HVFAC samples were calculated and compared with measured values (0.27-0.32), which were significantly below the recommended 1.0 index value. The prediction was relatively close to the measured values as the ratio between the calculated and measured I-index ranged between 0.89 and 1.14. Collected results of mechanical and radiological properties and performed calculations clearly prove that all 10 designed concretes with a certain type of fly ash are suitable for structural and non-structural applications both from a material and radiological point of view

[90] Self-created transobturator tape (TOT) vs standard industrially created TOT in the treatment of stress urinary incontinence: Should we change the concept?

Objective: To compare the benefit and cost of tension-free self-created transobturator tape (SCTOT) with the standard industrially created TOT (ICTOT) in the treatment of stress urinary incontinence (SUI). Methods: A prospective study of the treatment of SUI with SCTOT (98 patients) and ICTOT (77 patients) was performed. Two types of industrially created slings were used: the ‘T sling’ (Herniamesh, Torino, Italy), and the ‘TVT obturator’ (Johnson & Johnson, Somerville, NJ, USA). SCTOT (15 × 1 cm) was created from a polypropylene rectangular 30 × 30 cm macroporous polypropylene monofilament mesh weighing 48 g/m2 (Pelvimesh®, Herniamesh) and monofilament sutures. Sutures (polydioxanone [PDS] 2–0) were passed through both ends of the mesh stripe to make a ‘composite’ sling consisting of monofilament suture-sling-monofilament suture (Video). The Urogenital Distress Inventory (UDI-6), the Incontinence Impact questionnaire (IIC-7) and the International Continence Impact questionnaire short form (ICIQ5-SF) were used to evaluate symptoms before and after surgery. The Overactive Bladder Symptom Score (OABSS >8) was used to identify patients with mixed UI (MUI). Results: The follow-up period was 12 months. There was no statistically significant difference (P > 0.05) in objective cure between patients in the SCTOT group 84/98 (85.7%) and the ICTOT group 68/77 (88.3%). According to the IIC-7, UDI-6, ICIQ5-SF and OABSS symptom scores, significant improvement occurred in both groups, but it was better in the group with pure SUI than in the group with MUI, although it was not statistically significant. Symptom scores are shown in Tables 1 and 2. In all, 12 SCTOT were made from one polypropylene rectangular mesh priced at €60/piece. Compared to the price of the ICTOT (€400–700/piece) the SCTOT price is about 100-fold less. Conclusion: The results of the treatment with SCTOT are not inferior to the results of the treatment with ICTOT but are less expensive

Results of the modification of antireflux subserosal and submucosal implantation of the ureter into the rectosigmoid urinary reservoir after total cystectomy

Introduction. Uretero-intestinal anastomisis has a large influence on derivation quality. Objective. The aim of the study was to present the modified serous lined extramural Abol-Enein method of implantation of low quality ureter into the sigma-rectum pouch and comparison of the results with Le Duc implantation. Methods. From 1995 to 2009, 62 dilated ureter units were implanted in the detubularized rectosigmoid urinary reservoir. In 28 units Le Duc, and in 34 Abol-Enein method was done. Urinary fistula and ileus were considered as early complications, while late complications included stenosis and reflux pyelonephritis. Frequency of urination was considered as a parameter of functionality. Results. Transitory urine fistulae occurred only in the ureters implanted according to Le Duc technique in 4/28 (14.2%); the difference between the examined groups was close but still below the level of statistical significance (p=0.07). Ileus occurred with nearly equal frequency in both groups. Stenosis on the ureteral implantation place was significantly more frequent (p=0.04) in the Le Duc group 5/28 (21.7%) than in the Abol-Enein group 0/34 (0%). Refluxive pyelonephritis occurred in 3/34 (8.8%) of the Abol-Enein group, and in 5/28 (21.7%) of patients in the Le Duc group. Concerning the daily frequency, there was no difference between the examined groups. Conclusion. Uretero-intestinal anastomisis of dilated ureters through a serous-lined extramural tunnel decreases the risk of reflux in a considerable number of patients, with an acceptable level of complications. There are several advantages in comparison with Le Duc method

Adverse effects of pharmacological therapy of benign prostatic hyperplasia on sexual function in men

Introduction. The development of effective medications makes pharmacological therapy of BPH the dominant mode of treatment today. It improves urinary symptoms and prevents disease progression while producing side effects on male sexual function. Objective. The aim of the study is to present the effects of BPH pharmacological treatment on the occurrence of sexually adverse effects in men: changes in sexual desire, erectile, ejaculatory and the orgasmic function. Methods. A prospective study involving 156 BPH patients. The average age was 61.16±2.97. Four groups of 39 patients each were formed. The 4 groups were administered tamsulosin (alpha-blocker), finasteride (5-alpha reductase inhibitor), combination therapy (tamsulosin and finasteride) respectively, while the control group received no treatment. IPSS-QoL, IIEF and MSHQ-EjD questionnaires were used to evaluate the symptoms of voiding and sexual function. Follow-up examinations were performed 3 and 6 months into treatment. Results. Voiding symptoms improved in all groups receiving therapy. The side effects on the sexual function in all these groups include significant disorders of ejaculation and the orgasmic function. Ejaculation disorders: tamsulosin (-4.38±2.55; p<0.001), combined therapy (-3.89±2.84) and finasteride (-1.49±2.52). Orgasmic function disorders: tamsulosin (-1.03±1.94), combined therapy (-0.76±2.07) and finasteride (-0.54±1.68). Complete absence of ejaculation was experienced by 23% of patients on combined therapy, 15% on tamsulosin and 5% on finasteride. Conclusion. Pharmacological therapy of BPH improved voiding symptoms producing different effects on male sexual function. The main adverse effect on sexual function in men is the deterioration in ejaculation or the absence thereof. Clinical consideration of BPH should include the elements of male sexual function, patients’ age, the characteristics and effects of each group of drugs

Toward a codified design of recycled aggregate concrete structures: background for the new fib Model Code 2020 and Eurocode 2

This is the peer reviewed version of the following article: [Tošić, N, Torrenti, JM, Sedran, T, Ignjatović, I. Toward a codified design of recycled aggregate concrete structures: Background for the new fib Model Code 2020 and Eurocode 2. Structural Concrete. 2020; 1– 23], which has been published in final form at https://doi.org/10.1002/suco.202000512. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The use of recycled aggregate (RA) to produce recycled aggregate concrete (RAC) is a proven way of decreasing the consumption of natural aggregate (NA) and the landfilling of construction and demolition waste. However, adoption of codes for the design of RAC and RAC structures has been lacking. Within the framework of the new fib Model Code 2020 and Eurocode 2, provisions for RAC can be adopted. Therefore, in this study, a comprehensive and critical review of literature on RAC is performed as well as own meta-analyses of results. Material properties of RAC and structural behavior of reinforced and prestressed RAC members are analyzed, and based on the findings, code adjustments for RAC are proposed. The results show that, in order to incorporate RAC into design codes, changes are necessary in expressions for physical–mechanical properties (volumetric mass, modulus of elasticity, tensile strength, fracture energy, peak and ultimate strains, shrinkage strain and creep coefficient), durability-related properties (minimum concrete cover for durability) and structural behavior (shear strength of members not requiring shear reinforcement and deflections). The recommendations are formulated in terms of the total mass substitution ratio of RA that can be classified as Type A according to standard EN 206 for concrete. The results and findings presented herein can provide an important contribution toward the codification of RAC use and the wider utilization of RA in construction.Peer ReviewedPostprint (author's final draft

Flexural behaviour and ultimate bending capacity of high-volume fly ash reinforced concrete beams

Large number of studies analyzed physical and mechanical properties of high-volume fly ash concrete, but only a few discussed its structural behavior. Material properties are an important input parameter for structural analysis, but they are insufficient for reliable conclusions to be made. This study analyses flexural behavior of reinforced concrete beams made with 63% of low-calcium class F fly ash in total cementitious materials mass, using experimental method and analyzing current code predictions (EN 1992-1-1). The analysis was done by comparing beams made with two longitudinal reinforcement ratios, made with traditional cement concrete (OPC) and high-volume fly ash concrete (HVFAC), both corresponding to concrete class C30/37. Beams were tested in a four-point bending test measuring vertical displacement, crack development, concrete strains and longitudinal reinforcement strains. According to this research, the flexural performance of HVFAC beams is similar to flexural performance of corresponding OPC beams in terms of ultimate bending capacity. The significant difference was noticed regarding cracking extent that was higher in HVFAC beams. Available ultimate bending moments code predictions can be applied on HVFAC beams with similar precision and variation of results, like for OPC beams. However, this cannot be concluded for parameters depending on the cracking behaviour, like cracking moments or deflections. Results and analysis presented in this study indicate that HVFAC can be used in structural elements subjected dominantly to bending, like beams and slabs. More research regarding structural behavior of HVFAC using full-scale long-term tests is needed to develop larger database for reliability analysis.This work was supported by the Ministry for Education, Science and Technology, Republic of Serbia [Grant No TR36017]Peer ReviewedPostprint (author's final draft