Impact of a Hospital’s Antibiotic Stewardship Team on Fluoroquinolone Use at a Long- Term Care Facility

The primary objective of this study was to assess whether a hospital-based antimicrobial stewardship team (H-AST) from an unaffiliated hospital could decrease inappropriate fluoroquinolone use at a local, long-term care facility (LTCF). The H-AST created a multi-faceted intervention campaign that included antibiogram development, provider and family education, and a telephone hotline. Pre- and post-intervention mean defined daily doses per 1000 resident days for antimicrobials were calculated to determine the impact of the campaign. The campaign resulted in a 38.70% decrease in ciprofloxacin utilization, a 16.20% decrease in total FQ consumption, and an 11.68% in total antibiotic consumption. In addition, during the study period the rate of Clostridium difficile infection decreased by 19.47%. Collaboration with a H-AST had a positive impact on antibiotic prescribing at this LTCF

Bioconjugated gold nanoparticles enhance cellular uptake: a proof of concept study for siRNA delivery in prostate cancer cells

The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer

COMMUNITY PHARMACISTS\u27 COMMITMENT TO PREVENTIVE MEASURES DURING THE COVID-19 PANDEMIC IN LIGHT OF THE ECONOMIC CRISIS IN BEIRUT, LEBANON: A SIMULATED CLIENT STUDY

The burden on community pharmacists has dramatically increased since the COVID-19 pandemic, where the increased number of clients demands adhering to optimal infection protective measures. We aimed to investigate the level of adopted COVID-19 preventative measures by Lebanese community pharmacies and the influencing factors. One hundred community pharmacies in Beirut, were randomly selected and inspected by a simulated client. Signs of face-mask use, declaration of COVID-19 infection, and social distancing were observed in 62%, 48%, and 35% of pharmacies, respectively. Body temperature screening was absent. Only 20% of the pharmacies had limitations for the number of clients, and only 31% offered free disinfectants. Direct pharmacist-patient encounters were observed in 25% of pharmacies. Social distancing among pharmacists was practiced in only 8% of the pharmacies and 37% of pharmacists were not wearing facemasks. Female pharmacists, pharmacists \u3e 40 years, and large pharmacies were associated with a significantly higher score than male pharmacists, younger pharmacists, and smaller pharmacies (‎6.13 ± 1.73‎ vs. ‎4.21 ± 1.70‎, P = 0.004; ‎6.27 ± 1.55‎ vs. ‎4.40 ± 1.75‎, P = 0.03; and ‎6.73 ± 1.66‎ vs. ‎4.1 ± 1.74‎, P = 0.01; respectively). The adherence level of Lebanese community pharmacies to COVID-19 preventive measures is unsatisfactory. The economic crisis in addition to poor pharmacy education about infection control could be behind this level. The authorities are advised to wisely allocate the available resources, strengthen the monitoring process, and revise the pharmacy curriculum to include infection control

Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation

Metastatic prostate cancer is a leading cause of cancer-related death in men and current chemotherapies are largely inadequate in terms of efficacy and toxicity. Hence improved treatments are required. The application of siRNA as a cancer therapeutic holds great promise. However, translation of siRNA into the clinic is dependent on the availability of an effective delivery system. Gold nanoparticles (AuNPs) are known to be effective and non-toxic siRNA delivery agents. In this study, a stable gold nanosphere coated with poly(ethylenimine) (PEI) was prepared to yield PEI capped AuNPs (Au-PEI). The PEI was further conjugated with the targeting ligand anisamide (AA, is known to bind to the sigma receptor overexpressed on the surface of prostate cancer cells) to produce an anisamide-targeted nanoparticle (Au-PEI-AA). The resulting untargeted and targeted nanoparticles (Au-PEI and Au-PEI-AA respectively) were positively charged and efficiently complexed siRNA. Au-PEI-AA mediated siRNA uptake into PC3 prostate cancer cells via binding to the sigma receptor. In addition, the Au-PEI-AA·siRNA complexes resulted in highly efficient knockdown of the RelA gene (∼70%) when cells were transfected in serum-free medium. In contrast, no knockdown was observed in the presence of serum, suggesting that adsorption of serum proteins inhibits the binding of the anisamide moiety to the sigma receptor. This study provides (for the first time) proof of principle that anisamide-labelled gold nanoparticles can target the sigma receptor. Further optimisation of the formulation to increase serum stability will enhance its potential to treat prostate cancer

Gold nanoparticles enlighten the future of cancer theranostics

Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bioimaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance). As a new concept, termed “theranostics,” multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed

Production of Pseudomonas aeruginosa Intercellular Small Signaling Molecules in Human Burn Wounds

Pseudomonas aeruginosa has developed a complex cell-to-cell communication system that relies on low-molecular weight excreted molecules to control the production of its virulence factors. We previously characterized the transcriptional regulator MvfR, that controls a major network of acute virulence functions in P. aeruginosa through the control of its ligands, the 4-hydroxy-2-alkylquinolines (HAQs)—4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS). Though HHQ and PQS are produced in infected animals, their ratios differ from those in bacterial cultures. Because these molecules are critical for the potency of activation of acute virulence functions, here we investigated whether they are also produced during human P. aeruginosa acute wound infection and whether their ratio is similar to that observed in P. aeruginosa-infected mice. We found that a clinically relevant P. aeruginosa isolate produced detectable levels of HAQs with ratios of HHQ and PQS that were similar to those produced in burned and infected animals, and not resembling ratios in bacterial cultures. These molecules could be isolated from wound tissue as well as from drainage liquid. These results demonstrate for the first time that HAQs can be isolated and quantified from acute human wound infection sites and validate the relevance of previous studies conducted in mammalian models of infection

The effect of deworming on growth in one-year-old children living in a soil-transmitted helminth-endemic area of Peru: a randomized controlled trial

BACKGROUND:Appropriate health and nutrition interventions to prevent long-term adverse effects in children are necessary before two years of age. One such intervention may include population-based deworming, recommended as of 12 months of age by the World Health Organization in soil-transmitted helminth (STH)-endemic areas; however, the benefit of deworming has been understudied in early preschool-age children. METHODOLOGY/PRINCIPAL FINDINGS:A randomized, double-blind, placebo-controlled trial was conducted to determine the effect of deworming (500 mg single-dose crushed mebendazole tablet) on growth in one-year-old children in Iquitos, Peru. Children were enrolled during their routine 12-month growth and development clinic visit and followed up at their 18 and 24-month visits. Children were randomly allocated to: Group 1: deworming at 12 months and placebo at 18 months; Group 2: placebo at 12 months and deworming at 18 months; Group 3: deworming at both 12 and 18 months; or Group 4: placebo at both 12 and 18 months (i.e. control group). The primary outcome was weight gain at the 24-month visit. An intention-to-treat approach was used. A total of 1760 children were enrolled between September 2011 and June 2012. Follow-up of 1563 children (88.8%) was completed by July 2013. STH infection was of low prevalence and predominantly light intensity in the study population. All groups gained between 1.93 and 2.05 kg on average over 12 months; the average difference in weight gain (kg) compared to placebo was: 0.05 (95% CI: -0.05, 0.17) in Group 1; -0.07 (95%CI: -0.17, 0.04) in Group 2; and 0.04 (95%CI: -0.06, 0.14) in Group 3. There was no statistically significant difference in weight gain in any of the deworming intervention groups compared to the control group. CONCLUSIONS:Overall, with one year of follow-up, no effect of deworming on growth could be detected in this population of preschool-age children. Low baseline STH prevalence and intensity and/or access to deworming drugs outside of the trial may have diluted the potential effect of the intervention. Additional research is required to overcome these challenges and to contribute to strengthening the evidence base on deworming. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01314937)

EFFECT OF AUTOLOGOUS PLATELET-RICH PLASMA ON DISTRACTION OSTEOGENESIS IN THE MANDIBLE OF RABBITS: A MORPHOLOGIC AND MORPHOMETRIC APPROACH

Distraction osteogenesis of the jaws is a common surgical practice in the treatment of pediatric craniofacial deformities. Autologous platelet rich plasma (PRP) has been used to increase the healing potential of bones in humans during distraction osteogenesis. This article aims to study the morphometric and morphologic parameters resulting from the effect of PRP on bone healing after mandibular distraction in rabbits. Right mandibular distraction was performed in 12 rabbits divided equally into 2 groups. PRP and physiological saline were injected, according to a defined protocol, in the callus following distraction of the experimental and control groups respectively. The rabbits were sacrificed after a consolidation period of 45 days and the mandibles were surgically removed. Bone mineral density, radiographic analysis, mechanical properties and histological features of the lengthened bones were assessed using radiographic examination, dual X-ray absorptiometry, biomechanical testing and histology. Results showed that the regenerate bone density, the amount of trabeculation in addition to the bone mineral density and mineral content, as measured by absorptiometry, were better with PRP but not significantly different between groups. Two radiographs revealed a more consistent healing in the experimental mandibles compared with erratic outcomes in corresponding controls. Two of the latter could not be subjected to any mechanical testing because the mandibular parts, connected with fibrous tissue, were separated. Consequently, the biomechanical test depicted greater maximal loads in the experimental group. The histological studies exhibited more ossification and less connective tissue fibers in the experimental group. PRP accelerated healing of mandibles in rabbits following distraction and improved their biomechanical properties. These findings have significant clinical implications on reducing the period of consolidation of the mandibles which may not be immobilized like other bones for long period tim

Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: a formulation strategy for siRNA delivery

The potential of RNA interference (RNAi)-based therapeutics for cancer has received much attention; however, delivery of RNAi effectors, such as small interfering RNA (siRNA), remains an obstacle to clinical translation. Non-viral delivery vectors have been used extensively to enhance siRNA delivery. Recently, the potential of gold nanoparticles (AuNPs) for transporting drugs, proteins and genetic materials has been demonstrated. Previously, our laboratory synthesised positively charged, surfactant-free AuNPs in water by the reduction of gold (III) chloride (AuCl3) using hydroxylamine hydrochloride (NH2OH·HCl) in the presence of l-cysteine methyl ester hydrochloride (HSCH2CH(NH2)COOCH3·HCl) as a capping agent. These AuNPs, which achieve higher cell viability in comparison to cetyl trimethyl ammonium bromide (CTAB, a surfactant)-capped counterparts, have demonstrated potential for siRNA delivery. However, it is well known that systemic administration of cationic delivery systems without biological stablising moieties causes non-specific binding with negatively charged serum proteins, resulting in particle aggregation and opsonisation. Consequently, highly stable AuNPs capped with l-cysteine methyl ester hydrochloride conjugated to poly(ethylene glycol) (PEG) were synthesised in this study. PEGylation enhanced the biocompatibility of the AuNPs by reducing toxicity in a range of cell types, by inhibiting interaction with serum proteins thus avoiding aggregation, and, by providing protection against degradation by nucleases. Moreover, these PEGylated AuNPs formed nanoparticles (NPs) with siRNA (which was first compacted with protamine), and had a diameter within the nanoscale range (∼250nm) and a near neutral surface charge (∼10mV). In the future a bifunctional PEG chain on the AuNPs (i.e., SH-PEG-NH2, SH-PEG-COOH) will be used to facilitate conjugation of a targeting ligand to enhance cell specific uptake