Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r2 > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a Tmax of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC0-∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone

Towards trustworthy computing on untrustworthy hardware

Historically, hardware was thought to be inherently secure and trusted due to its obscurity and the isolated nature of its design and manufacturing. In the last two decades, however, hardware trust and security have emerged as pressing issues. Modern day hardware is surrounded by threats manifested mainly in undesired modifications by untrusted parties in its supply chain, unauthorized and pirated selling, injected faults, and system and microarchitectural level attacks. These threats, if realized, are expected to push hardware to abnormal and unexpected behaviour causing real-life damage and significantly undermining our trust in the electronic and computing systems we use in our daily lives and in safety critical applications. A large number of detective and preventive countermeasures have been proposed in literature. It is a fact, however, that our knowledge of potential consequences to real-life threats to hardware trust is lacking given the limited number of real-life reports and the plethora of ways in which hardware trust could be undermined. With this in mind, run-time monitoring of hardware combined with active mitigation of attacks, referred to as trustworthy computing on untrustworthy hardware, is proposed as the last line of defence. This last line of defence allows us to face the issue of live hardware mistrust rather than turning a blind eye to it or being helpless once it occurs. This thesis proposes three different frameworks towards trustworthy computing on untrustworthy hardware. The presented frameworks are adaptable to different applications, independent of the design of the monitored elements, based on autonomous security elements, and are computationally lightweight. The first framework is concerned with explicit violations and breaches of trust at run-time, with an untrustworthy on-chip communication interconnect presented as a potential offender. The framework is based on the guiding principles of component guarding, data tagging, and event verification. The second framework targets hardware elements with inherently variable and unpredictable operational latency and proposes a machine-learning based characterization of these latencies to infer undesired latency extensions or denial of service attacks. The framework is implemented on a DDR3 DRAM after showing its vulnerability to obscured latency extension attacks. The third framework studies the possibility of the deployment of untrustworthy hardware elements in the analog front end, and the consequent integrity issues that might arise at the analog-digital boundary of system on chips. The framework uses machine learning methods and the unique temporal and arithmetic features of signals at this boundary to monitor their integrity and assess their trust level

NANOPRECIPITATION TECHNIQUE FOR PREPARATION OF STERICALLY STABILIZED RISPERIDONE NANOSUSPENSION: IN VITRO AND IN VIVO STUDY

Objective: Risperidone is an atypical antipsychotic drug used to treat schizophrenia; however it suffers from a poor aqueous solubility, which delays its onset of action. Therefore, the purpose of the present study is to utilize the nanotechnology to formulate nanoparticles that enhance the dissolution and hence the bioavailability of risperidone.Methods: Nanosuspensions were prepared by nano precipitation method in the presence of selected stabilizers at different concentrations. The nanosuspensions were evaluated for their particle size, zeta potential, drug content and In vitro drug dissolution. The selected formula was freeze dried and characterized by scanning electron microscopy (SEM), fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffractometry studies (XRD) and pharmacokinetic study.Results: The in vitro dissolution showed higher drug release compared to the pure drug. The optimum formula has an average particle size of 215.56±12.65 nm and zeta potential of-19.84±2.55mV. The bioavailability parameters in the rabbits were enhanced by 2 folds when compared with the marketed tablets (Risperidal®).Conclusion: Nanoprecipitation method was successfully employed to produce stable risperidone nanosuspension by using the proper stabilizer (pluronic F 127). Risperidone nanoparticles may be a promising formula that improves the dissolution and hence oral bioavailability of poorly water soluble risperidone. Keywords: Risperidone, Nanosuspension, Pluronic F127, Nanoprecipitation, Bioavailabilit

Thoracoscopic excision of asymptomatic posterior mediastinal ganglioneuroma. A case series study

Background Posterior mediastinal ganglioneuroma is the most frequent type of neurogenic tumors, and usually it is asymptomatic. The surgical approach to excise it may differ from center to center based on the surgeon's experience as well as the size of tumor. We aim to present our center's experience and short-term outcomes in surgical excision of posterior mediastinal ganglioneuroma. Methods This retrospective case series study, from June 2019 till December 2022, included 9 asymptomatic patients with mean age of 31± 5 years who expressed lesion in the posterior mediastinum. The mean size of the tumor was&nbsp;&nbsp; 5.3±3.6 cm in maximal dimensions.&nbsp; Results There were 7 males and 2 females with mean age was 31± 5 years,&nbsp; the excision by video-assisted thoracoscopy (VATS)&nbsp; was&nbsp; employed in 8 patients and conventional thoracotomy was carried out in 1 case.&nbsp; The mean operative time was 57±14 minutes with mean operative blood loss 50±10 ml. The mean postoperative chest tube drainage was 120±80 ml and no complications related to the procedures were observed. The average time of hospital stay after VATS treatment was 2 days, while after thoracotomy it was 5 days and patient suffered from ptosis that eventually recovered after 1 month with supportive treatment. Histopathological examination confirmed benign nature of ganglioneuroma in all cases. Conclusions Thoracoscopic excision of asymptomatic posterior mediastinal neurogenic tumor is safe, feasible and reduces postoperative pain, however, open technique might be considered for large-sized tumor to minimize the possible complications

A framework for understanding the evolution of relationship quality and the customer relationship development process.

This paper attempts to develop and empirically test a conceptual model of relationship quality (RQ) in the financial sector from the perspective of the individual consumer (B2C). Based on a review of RQ research, the paper proposes a model of RQ from the customer perspective using the constructs most often examined in empirical RQ research (customer satisfaction, trust and commitment) and considers the relative importance of these dimensions within the stages of the relationship development process (RDP). A survey of 150 bank customers was undertaken in Egypt and the results tested using structural equation modelling. Respondents were selected on a convenience sampling basis and administered a questionnaire instrument for completion. The findings show that there is a strong relationship between the customer's perceived relationship development phase and the perceived RQ. An important contribution of this paper lies in the alternative conceptualization of RQ as composed of three dynamic dimensions which are dependent on the RDP phase or stage. A second contribution is methodological and relates to the development of a modified scale to identify the relationship phases of customers. To the best of the researchers' knowledge, these contributions are unique and have not been made previously to the body of knowledge on service relationship management

The influence of anger and sunk cost effect on project status: an extension to portfolios of projects

This research focuses on anger and sunk cost effects as sources of cognitive bias and also portfolio interactions in relation to the retention/termination decisions on projects. Departing from a traditionally narrow and quantitative perspective of traditional project appraisal, this study investigates a wider psychological view of investment project decisions within four project management groups. The thesis emphasises that the role of the specific emotion of anger is influenced by the past sunk cost of projects and the effects of a portfolio of projects across the whole firm. In the sense that project retention is perceived to be a positive outcome of anger, it has arguably been neglected in empirical entrepreneurship and strategic decision-making research, but this study claims that the retention and termination of projects may be analysed using psychological theories of emotions. A case study based on a Palestinian holding company, therefore, investigates the influence of anger, the sunk cost effect and portfolio considerations on project retention and termination. The holding company under study operates in an uncertain political context likely to be a rich laboratory eliciting high levels of anger, thus highlighting their role. This study conducts fifteen emotion assessment surveys using a STAXI-2 inventory and content and thematic analyses of fifteen interviews, adopting multi-levels of analysis, and claims to make contributions to the entrepreneurship, strategic decision-making and psychology literatures. The analysis reports that anger has an important emotional influence on decisions. It demonstrates three main findings, i.e. mostly positive associations between anger, the sunk cost effect and portfolio considerations and project retention. It also presents four subsidiary findings. Hope emerged as the second most important emotion and is claimed to be associated with project retention. Other emotions also co-exist with anger and may have influenced retention decisions, and findings reveal an association between corporate identity (i.e. a factor emerged from data) and project retention. Finally, in an atypical case, anger is found to encourage project termination

BIODEGRADABLE LIPOSOMES FOR ACYCLOVIR-GOLD NANOPARTICLES AS AN EFFICIENT CARRIERFOR ENHANCED TOPICAL DELIVERY

Objective: Gold nanoparticles and nanoliposomes are effective new technology in delivering the bioactive agents and enhancing their performance by increasing the bioavailability. The goal of the present study was the formulation of liposome for the use as a carrier for nanogold conjugated with acyclovir (ACV), an antiviral drug, to enhance ACV delivery.Methods: The gold nanoparticles were used as a capping agent for ACV and sodium citrate was used as reducing agent for the gold. Transmission electron microscopy was used for characterization and to study the morphological and structural properties of drug-metallic nanostructures. Nanoliposomes were formulated using different molar ratios of a positive charge inducer (stearyl amine) or a negative charge inducer (diacetyl phosphate), lecithin, cholesterol and Span 60.Results: Gold nanoparticles with a particle size of 10–20 nm were formed. This small size of the formed particles has a clear effect in reducing the gold nanoparticles toxicity and enhancing the cellular uptake. The amount of sodium citrate used in this preparation influences the size of the gold nanoparticle. The present study employed 1% trisodium citrate that contains a carboxylic group and this carboxylic group works as a reducing and capping agent to synthesize ACV-gold nanoparticles conjugate. Liposomal formula F6 had the highest entrapment efficiency approaching 42%, the low particle size of 160 nm, and zeta potential of 43.5 mV.Conclusion: It is evident from the study that the liposomes can be used as a carrier of ACV conjugated with gold nanoparticles. This new strategy could be used successfully in the treatment of viral infection