Recent advances in nanosystems and strategies for vaginal delivery of antimicrobials

Vaginal infections such as bacterial vaginosis (BV), chlamydia, gonorrhea, genital herpes, candidiasis, and trichomoniasis affect millions of women each year. They are caused by an overgrowth of microorganisms, generally sexually transmitted, which in turn can be favored by alterations in the vaginal flora. Conventional treatments of these infections consist in systemic or local antimicrobial therapies. However, in the attempt to reduce adverse effects and to contrast microbial resistance and infection recurrences, many efforts have been devoted to the development of vaginal systems for the local delivery of antimicrobials. Several topical dosage forms such as aerosols, lotions, suppositories, tablets, gels, and creams have been proposed, although they are sometimes ineffective due to their poor penetration and rapid removal from the vaginal canal. For these reasons, the development of innovative drug delivery systems, able to remain in situ and release active agents for a prolonged period, is becoming more and more important. Among all, nanosystems such as liposomes, nanoparticles (NPs), and micelles with tunable surface properties, but also thermogelling nanocomposites, could be exploited to improve local drug delivery, biodistribution, retention, and uptake in vulvovaginal tissues. The aim of this review is to provide a survey of the variety of nanoplatforms developed for the vaginal delivery of antimicrobial agents. A concise summary of the most common vaginal infections and of the conventional therapies is also provided

Revisiting the mechanical limited-slip differential for high-performance and race car applications

This paper provides a comprehensive revision of the working principles and limitations of the mechanical limited-slip differential (LSD), a passive device used to improve traction capabilities and to extend the performance envelope of high-performance road cars, racing and rally cars. The LSD has been in use for decades. However, according to the authors’ experience, its impact on vehicle dynamics appears to be somewhat neglected in the literature and often misunderstood, especially in the semi-pro racing community. Current research on the subject is usually focused on side aspects and/or on modern control applications such as active differentials and torque-vectoring systems. These state-of-the-art technologies still rely on the same principles of the LSD, which should therefore be fully explained. The authors intend to fill this gap by starting with a comprehensive literature review. Then, an intuitive explanation of the impact of limited slip systems on vehicle behaviour is proposed with simple mathematical models and examples to integrate what seems to be missing. The peculiar shape of the torque-sensitive LSD working zone on the torque bias diagram is explained to an unprecedented level of detail. Real-world application examples are provided, including data recorded on a single-seater racecar integrated with examples based on a virtual model

Towards T.R.I.C.K. 2.0 – A tool for the evaluation of the vehicle performance through the use of an advanced sensors system

In the last years, the tire technological development has played a fundamental role in motorsport and in automotive industry. The tire contact patch forces have a great influence on the vehicle behavior, so their correct estimation is a crucial task to understand how to improve the car performance. In order to identify the tire interaction characteristic, it is also necessary to use a procedure that allows the correct evaluation of the slip angles in the different operating conditions. This paper presents an evolution of the T.R.I.C.K. tool developed by the UniNa vehicle dynamics research group. In the first version of this tool an 8 degree of freedom vehicle model has been implemented and, starting from the experimental data acquired, the T.R.I.C.K. calculates the interaction forces and the tire slips using the equilibrium equations. Using more car parameters and further data obtained from track sessions and dedicated tests, in the presented release of the tool, new formulations have been developed for a more accurate calculation of the tire-road forces. The effectiveness of the treatments is assessed using experimental data and the simulator outputs. The new formulations introduced in this paper allows, depending on the availability of additional vehicle data and acquisition sensors, to estimate the interaction forces with different and more accurate methodologies than the equilibrium equations, while retaining very reduced simulation times. In this way it is possible to carry out a more precise study of vehicle dynamics with the possibility of investigating and significantly improving performance

Assessment of in‐situ gelling microemulsion systems upon temperature and dilution condition for corneal delivery of bevacizumab

Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron® 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic® F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76–1.56% BVZ diffused, 4–20% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 × 103 to more than 100 × 103 mPa·s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems

The role of repetitive transcranial magnetic stimulation (rTMS) in the treatment of behavioral addictions: Two case reports and review of the literature

none9noBackground Several behaviors, besides consumption of psychoactive substances, produce short-term reward that may lead to persistent aberrant behavior despite adverse consequences. Growing evidence suggests that these behaviors warrant consideration as nonsubstance or “behavioral” addictions, such as pathological gambling, internet gaming disorder and internet addiction. Case presentation Here, we report two cases of behavioral addictions (BA), compulsive sexual behavior disorder for online porn use and internet gaming disorder. A 57-years-old male referred a loss of control over his online pornography use, started 15 years before, while a 21-years-old male university student reported an excessive online gaming activity undermining his academic productivity and social life. Both patients underwent a high-frequency repetitive transcranial magnetic stimulation (rTMS) protocol over the left dorsolateral prefrontal cortex (l-DLPFC) in a multidisciplinary therapeutic setting. A decrease of addictive symptoms and an improvement of executive control were observed in both cases. Discussion Starting from these clinical observations, we provide a systematic review of the literature suggesting that BAs share similar neurobiological mechanisms to those underlying substance use disorders (SUD). Moreover, we discuss whether neurocircuit-based interventions, such as rTMS, might represent a potential effective treatment for BAs.openCuppone, D; Gómez Pérez, L J; Cardullo, S; Cellini, N; Sarlo, M; Soldatesca, S; Chindamo, S; Madeo, G; Gallimberti, LCuppone, D; Gómez Pérez, L J; Cardullo, S; Cellini, N; Sarlo, M; Soldatesca, S; Chindamo, S; Madeo, G; Gallimberti,

Vehicle sideslip estimation for four-wheel-steering vehicles using a particle filter

The availability of the most relevant vehicle states is crucial for the development of advanced vehicle control systems and driver assistance systems. Specifically the vehicle sideslip angle plays a key role, yet this state is unpractical to measure and still not straightforward to estimate. This paper investigates a particle filter approach to estimate the chassis sideslip angle of road vehicles. The filter relies on a physical model of the vehicle and on measurements available from cheap and widespread sensors including inertial measurement unit and steering wheel angle sensor(s). The approach is validated using experimental data collected with the research platform RoboMobil (RoMo), a by-wire electric vehicle with wheel-individual traction and steering actuators. Results show that the performance of the proposed particle filter is satisfactory, and indicate directions for further improvement

Vehicle sideslip angle estimation using Kalman filters: modelling and validation

The knowledge of the vehicle sideslip angle provides useful information about the state of the vehicle and it is often considered to increase the performance of the car as well as to develop safety systems, especially in the vehicle equipped with Torque Vectoring control systems. This paper describes two methods, based on the use of Kalman filters, to estimate the vehicle sideslip angle and the tire forces of a vehicle starting from the longitudinal and yaw velocity data. In particular, these data refer to on-track testing of a Range Rover Evoque performing ramp steer maneuvers at constant speed. The results of the sideslip estimation method are compared with the actual vehicle sideslip measured by a Datron sensor and are also used to estimate the tire lateral forces

Revisiting the mechanical limited-slip differential for high-performance and race car applications

This paper provides a comprehensive revision of the working principles and limitations of the mechanical limited-slip differential (LSD), a passive device used to improve traction capabilities and to extend the performance envelope of high-performance road cars, racing and rally cars. The LSD has been in use for decades. However, according to the authors’ experience, its impact on vehicle dynamics appears to be somewhat neglected in the literature and often misunderstood, especially in the semi-pro racing community. Current research on the subject is usually focused on side aspects and/or on modern control applications such as active differentials and torque-vectoring systems. These state-of-the-art technologies still rely on the same principles of the LSD, which should therefore be fully explained. The authors intend to fill this gap by starting with a comprehensive literature review. Then, an intuitive explanation of the impact of limited slip systems on vehicle behaviour is proposed with simple mathematical models and examples to integrate what seems to be missing. The peculiar shape of the torque-sensitive LSD working zone on the torque bias diagram is explained to an unprecedented level of detail. Real-world application examples are provided, including data recorded on a single-seater racecar integrated with examples based on a virtual model

A SIMULATION TOOL FOR OPTIMIZATION AND PERFORMANCE PREDICTION OF A GENERIC HYBRID ELECTRIC SERIES POWERTRAIN

Hybrid and electric vehicles are taking an increasingly important slice of the market, gaining much interest from major car manufacturers which have decided to invest in this sector, taking as example the pioneers like Toyota. The key factor to hybrid and electric vehicle success is a good overall mileage achieved from the battery back or powertrain. The purpose of this work is to provide a support to design, testing, and development of such vehicles through the implementation of a mathematical model in order to simulate the operation and predict the performance of a generic ground vehicle equipped with either a purely electric or a hybrid-electric type powertrain. The model should enable the user to estimate the impact of various control strategies on mileage range, efficiency, energy consumption, etc. The model should also allow for a significant time to market reduction with all the related benefits in terms of cost etc. A validation is also provided, based on the application of this tool on a so-called micro-car (0.5t GVW class). Thanks to a joint research project with the manufacturer it has been possible to compare model results with real-world data directly obtained during road testing with the help of a data acquisition system