Squeezing out the last 1 nanometer of water: A detailed nanomechanical study

In this study, we present a detailed analysis of the squeeze-out dynamics of nanoconfined water confined between two hydrophilic surfaces measured by small-amplitude dynamic atomic force microscopy (AFM). Explicitly considering the instantaneous tip-surface separation during squeezeout, we confirm the existence of an adsorbed molecular water layer on mica and at least two hydration layers. We also confirm the previous observation of a sharp transition in the viscoelastic response of the nanoconfined water as the compression rate is increased beyond a critical value (previously determined to be about 0.8 nm/s). We find that below the critical value, the tip passes smoothly through the molecular layers of the film, while above the critical speed, the tip encounters "pinning" at separations where the film is able to temporarily order. Pre-ordering of the film is accompanied by increased force fluctuations, which lead to increased damping preceding a peak in the film stiffness once ordering is completed. We analyze the data using both Kelvin-Voigt and Maxwell viscoelastic models. This provides a complementary picture of the viscoelastic response of the confined water film

The accumulation of particles in ureteric stents is mediated by flow dynamics: Full-scale computational and experimental modeling of the occluded and unoccluded ureter

Ureteric stents are clinically deployed to restore urinary drainage in the presence of ureteric occlusions. They consist of a hollow tube with multiple side-holes that enhance urinary drainage. The stent surface is often subject to encrustation (induced by crystals-forming bacteria such as Proteus mirabilis) or particle accumulation, which may compromise stent's drainage performance. Limited research has, however, been conducted to evaluate the relationship between flow dynamics and accumulation of crystals in stents. Here, we employed a full-scale architecture of the urinary system to computationally investigate the flow performance of a ureteric stent and experimentally determine the level of particle accumulation over the stent surface. Particular attention was given to side-holes, as they play a pivotal role in enhancing urinary drainage. Results demonstrated that there exists an inverse correlation between wall shear stress (WSS) and crystal accumulation at side-holes. Specifically, side-holes with greater WSS levels were those characterized by inter-compartmental fluid exchange between the stent and ureter. These "active " side-holes were located either nearby ureteric obstructions or at regions characterized by a physiological constriction of the ureter. Results also revealed that the majority of side-holes (> 60%) suffer from low WSS levels and are, thus, prone to crystals accumulation. Moreover, side-holes located toward the proximal region of the ureter presented lower WSS levels compared to more distal ones, thus suffering from greater particle accumulation. Overall, findings corroborate the role of WSS in modulating the localization and extent of particle accumulation in ureteric stents. (C) 2022 Author(s)

Development and In vitro Evaluation of Betahistine Adhesive-Type Transdermal Delivery System

Purpose: To develop a transdermal betahistine (BTH) delivery system using different pressure sensitive adhesives (PSAs) including acrylics, polyisobutylene and styrenic rubber solution.Methods: Formulations were prepared by solvent casting and adhesive transfer method. PSAs - acrylate vinylacetate (AVA), hydrophilic acrylate (HA), acrylic non-curing (ANC), polyisobutylene (PIB), and tackified styrenic rubber solution (TSR) - were evaluated for their suitability in terms of miscibility, maximum drug loading, effect on tack property and in vitro permeation through excised guinea pig skin. Furthermore, one of the PSAs was tested in relation to effect of penetration enhancers on tack property, in vitro permeation, in vivo patch adhesion performance and stability.Results: Only formulations prepared with AVA and HA were stable. Increased drug loading in these PSAs significantly reduced tack. In vitro permeation data across guinea pig skin demonstrated that BTH flux from from the formulation containing HA (F1) was significantly (p < 0.001) higher than that containing AVA (F2). Formulations containing 2 % enhancer showed good tack. Specifically, the formulation containing 2 % oleic acid as enhancer not only showed the highest permeation but also good tack property, non-irritancy for up to 36 h and stability under accelerated conditions.Conclusion: The formulation containing HA as the PSA and 2 % oleic acid as enhancer demonstrated a good potential for further development to an adhesive-type transdermal delivery system for BTH.Keywords: Meniere’s syndrome, Transdermal delivery, Betahistine, Pressure-sensitive adhesives, Penetration enhancersTropical Journal of Pharmaceutical Research December 2010; 9 (6): 516-52

Endovascular control of haemorrhagic urological emergencies: an observational study

BACKGROUND: Transarterial embolisation (TAE) is an effective method in control of haemorrhage irrespective of the nature of urological emergency. As the technique and technology have evolved, it is now possible to perform highly selective embolisation. The aim of this study was to critically appraise feasibility and efficacy of therapeutic TAE in control of haemorrhagic urological emergencies using selective and non-selective embolisation. Specifically, we aimed to assess the impact of timing of embolisation on the requirement of blood transfusion and long-term morphological and functional follow-up of embolised organs. METHODS: This is a single institutional observational study carried out between March 1992 and March 2006. Records of all patients who underwent selective and non-selective angioembolisation to control bleeding in urological emergencies were reviewed. Data on success rate, periprocedural complications, timing of embolisation, requirement of blood transfusion and the long-term morphological and functional outcomes of embolised organs was recorded. RESULTS: Fourteen patients underwent endovascular control of bleeding as a result of trauma, iatrogenic injury and spontaneous perinephric haemorrhage during a period of 14 years. All these patients would have required emergency open surgery without the option of embolisation procedure. The mean time between the first presentation and embolisation was 22 hours (range 30 minutes to 60 hours). Mean pre-embolisation transfusion requirement was 6.8 units (range 0–22 units). None of the patients with successful embolisation required post-procedural blood transfusion. Permanent haemostasis was achieved in all but one patient, who required emergency nephrectomy. There were no serious procedure related post-embolisation complications. CONCLUSION: Endovascular control using transarterial angioembolisation is an effective method for managing haematuria or haemorrhage in urological emergencies. Wherever and whenever indicated, this option should be considered early in the management of these cases

Scoping Review of Experimental and Clinical Evidence and Its Influence on Development of the Suction Ureteral Access Sheath

The ureteral access sheath (UAS) has been a boon and a bane in flexible ureteroscopy (FURS), with its merits and demerits well established. Its design and dimensions were instrumental in reshaping the way flexible scopes were used and were key adjuncts to establishing retrograde intrarenal surgery (RIRS) as a standard of care in the endourological management of renal stones. With the ever-changing landscape of RIRS over the decades shaped by technological advancements in lasers and flexible scopes, the UAS has also continuously evolved. The utility of suction in endourology has recently changed the way RIRS is performed and is a game changer for FURS outcomes. With strong clinical and experimental evidence to support its use, the UAS has undergone a transformative change in the recent past, with its ability to monitor intrarenal pressure and provide a superior vacuum-cleaner effect that improves the trifecta of RIRS, namely an improved single-stage stone-free rate (SFR), minimise complications, and reduce reinterventions. Our comprehensive review outlines the key clinical and experimental evidence and traces the developments that were key to modifying the traditional UAS into a flexible and navigable suction ureteric access sheath (FANS) and highlights how the design and modifications, in turn, influence the ability to push the boundaries of RIRS

Does age impact outcomes of retrograde intrarenal surgery in the elderly? Results from 366 patients from the FLEXible ureteroscopy outcomes registry (FLEXOR)

Background: There has been a consistent increase in the last decades in prevalence of renal stones in elderly. Aims: To evaluate outcomes of retrograde intrarenal surgery (RIRS) for renal stones in elderly and factors associated with postoperative complications and residual fragments (RFs). Methods: Data from 12 centers were retrospectively reviewed. Inclusion criteria: ≥ 75 years, renal stones only, normal renal anatomy. Patients were divided into three groups; Group 1: patients aged 75–79 years; Group 2: age 80–84 years; Group 3: age ≥ 85 years. Multivariable logistic regression analyses were performed to assess factors associated with perioperative complications, sepsis, and RFs. Results: 366 patients were included. There were 189 patients in Group 1, 113 in Group 2, and 64 in Group 3. There was no difference between groups regarding stone features and total surgical time. Median length of stay was significantly longer in Group 3 (6.0 days, vs 2.0 days in Group 2 vs 2.5 days in Group 1, p = 0.043). There was no significant difference in postoperative complications and RFs between the groups. At multivariable logistic regression analysis, female gender (OR 2.82) and maximum stone diameter (OR 1.14) were associated with higher odds of sepsis, while surgical time (OR 1.12) and the use of a reusable ureteroscope (OR 6.51) with overall complications. Stone size (OR 1.23) was associated with higher odds of RFs. Conclusion: RIRS showed safety and efficacy for kidney stones in elderly patients. Surgical time should be kept as short as possible to avoid higher odds of postoperative complications, particularly in females

First urology simulation boot camp in the United Kingdom

Objective: Simulation is now firmly established in modern surgical training and is applicable not only to acquiring surgical skills but also to non-surgical skills and professionalism. A 5-day intensive Urology Simulation Boot Camp was run to teach emergency procedural skills, clinical reasoning, and communication skills using clinical scenario simulations, endoscopic and laparoscopic trainers. This paper reports the educational value of this first urology boot camp. Subjects and methods: Sixteen urology UK trainees completed pre-course questionnaires on their operative experience and confidence level in common urological procedures. The course included seven modules covering basic scrotal procedures, laparoscopic skills, ureteroscopy, transurethral resection of the prostate and bladder tumour, green light laser prostatectomy, familiarisation with common endoscopic equipment, bladder washout to remove clots, bladder botox injection, setting up urodynamics. Emergency urological conditions were managed using scenarios on SimMan®. The main focus of the course was hands-on training using animal models, bench-top models and virtual reality simulators. Post-course assessment and feedback on the course structure and utility of knowledge gained together with a global outcome score was collected. Results: Overall all the sections of feedback received score of over 4.5/5, with the hands-on training on simulators getting the best score 4.8/5. When trainees were asked “The training has equipped me with enhanced knowledge, understanding and skills,” the average score was 4.9/5.0. The vast majority of participants felt they would recommend the boot camp to future junior trainees. Conclusion: This first UK Urology Simulation Boot Camp has demonstrated feasibility and effectiveness in enhancing trainee’s experience. Given these positive feedbacks there is a good reason to expect that future courses will improve the overall skills of a new urology trainee

A comparison of sexual behaviour and attitudes of healthy adolescents in a Danish high school in 1982, 1996, and 2001

AIM: To assess changes in sexual behaviour among students at a high school in Denmark from 1982 to 2001. METHODS: An anonymous self-administered questionnaire was used to compare data from three identical cross-sectional surveys performed in 1982, 1996, and 2001. RESULTS: Girls: More girls reported their first sexual intercourse before their 16th birthday in 2001 (42%) than in 1996 (29%) In 1982 it was also 42% (Chi-square for trend: p = 0.003). Fewer girls with no regular partner used condoms for their personal protection in 2001 (2%) than in 1996 (9%) and 1982 (0%) (Chi-square for trend p = 0.016). The proportion of girls with no regular partner who considered protection from sexually transmitted disease important for their choice of contraception was 39% in 2001 compared with 71% in 1996 and only 10% in 1982 (Chi-square for trend: p < 0.0001). Boys: More boys reported sexual debut before their 16th birthday in 2001 (40%) than in 1996 (37%) and 1982 (24%) (Chi-square for trend: p = 0.023). For boys with no regular partner, condom was preferred for personal protection by 85% in 2001, 91% in 1996 and 61% in 1982 (Chi-square for trend p = 0.007). Protection against sexually transmitted infection declined, especially among boys with no regular partner, from 51% in 2001 to 72% in 1996 and 21% in 1982 Chi-square for trend: p < 0.0001). The tendency towards earlier sexual debut and less use of safe sex practices to protect against sexually transmitted infections (STI) was accompanied by a rise in the number of detected STIs during this period. CONCLUSIONS: The period from 1982 to 1996 during which sexual attitudes were directed toward safer sex seems to have given way to a reverse trend in the period from 1996 to 2001. These findings may have significant implications for health care authorities organising preventive strategies for healthy adolescents

Equilibrium molecular thermodynamics from Kirkwood sampling.

We present two methods for barrierless equilibrium sampling of molecular systems based on the recently proposed Kirkwood method (J. Chem. Phys. 2009, 130, 134102). Kirkwood sampling employs low-order correlations among internal coordinates of a molecule for random (or non-Markovian) sampling of the high dimensional conformational space. This is a geometrical sampling method independent of the potential energy surface. The first method is a variant of biased Monte Carlo, where Kirkwood sampling is used for generating trial Monte Carlo moves. Using this method, equilibrium distributions corresponding to different temperatures and potential energy functions can be generated from a given set of low-order correlations. Since Kirkwood samples are generated independently, this method is ideally suited for massively parallel distributed computing. The second approach is a variant of reservoir replica exchange, where Kirkwood sampling is used to construct a reservoir of conformations, which exchanges conformations with the replicas performing equilibrium sampling corresponding to different thermodynamic states. Coupling with the Kirkwood reservoir enhances sampling by facilitating global jumps in the conformational space. The efficiency of both methods depends on the overlap of the Kirkwood distribution with the target equilibrium distribution. We present proof-of-concept results for a model nine-atom linear molecule and alanine dipeptide.This research was funded by the European Research Council and EPSRC grant EP/I001352/1. Y.O. was supported, in part, by the JSPS Grant-in-Aid for Scientific Research on Innovative Areas (“Dynamical Ordering and Integrated Functions”).This is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/acs.jpcb.5b01800