Potential strategies for the eradication of multi-drug resistant Gram-negative bacterial infections

Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections. </jats:p

Quantification of Linalool in 3D Printed Fast-Dissolving Oral Films by A High-Pressure Liquid Chromatography Method

Introduction: Linalool has shown inhibitory effects against Candida albicans. Microbial resistance is developing towards the current antifungal drugs. Therefore, an oral formulation of linalool oil may be used to effectively treat oral thrush. A wide range of patients can use fast-dissolving oral films (FDFs). Three-dimensional printing (3DP) may be utilised for the manufacture of FDFs. Aims: to formulate linalool in FDFs and quantify it using high-pressure liquid chromatography (HPLC). Methods: A powder formulation containing linalool (5%w/w) was prepared and filaments were produced at 75°C and printed at 185°C. The films were dissolved either in methanol or deionised water, and linalool was quantified in the aqueous solutions. The mobile phase of a previously reported HPLC method was modified to quantify linalool in the aqueous solutions. The HPLC method was validated by measuring linalool in standard methanol and aqueous solutions. Results: Preparing aqueous solutions of filaments and films provided less variability in the analyses. 3D-printed FDFs had an average weight of 78.44 ± 6.84 mg. Applying the HPLC method revealed that the amounts of linalool changed from a theoretical 25 mg (per 0.5 g of filament) to the range of 23.98 ± 1.22 to 33.79 ± 2.43 mg. In contrast, the amounts of linalool were changed in films from theoretical 25 mg (per 0.5 g of film) to 13.82 ± 3.24 mg to 21.04 ± 0.92 mg. These observations indicated the evaporation of linalool considerably during printing at 185 °C. Conclusion: This work found that linalool FDFs should be printed at temperatures lower than 185 °C and dissolved in deionised water for better HPLC analytical consistency

Self-assembling Ultrashort NSAID-Peptide Nanosponges: Multifunctional Antimicrobial and Anti-inflammatory Materials

This paper outlines the design, synthesis and characterisation of innovative NSAID-peptide gelators which demonstrate antimicrobial and anti-inflammatory properties and have potential use as multifunctional materials for biomedical applications.</p

KidzMed e-learning to upskill student pharmacists to teach pill swallowing to children

Background: Appropriate medication use is essential in ensuring optimal pharmacotherapeutic outcomes. It is mistakenly assumed that adults can swallow solid oral dosage forms (SODFs, e.g. tablets/capsules colloquially referred to as ‘pills’), without difficulty and that children cannot. KidzMed is a ‘pill swallowing’ training programme designed to teach effective SODF use in patients of all ages. It may be utilised by healthcare professionals to assist patients taking SODFs. E-learning was essential for training during COVID pandemic to reduce viral transmission. The aim of this study was to explore UK student pharmacists views of e-learning to support swallowing solid oral dosage forms. Methods: This study used pre- and post-intervention online surveys on Microsoft Forms to evaluate self-directed eLearning about pill swallowing on MPharm programmes at three UK Universities using a 13-item survey. A combination of five-point Likert Scales and free-text items were used. The eLearning was available via the virtual learning environment at the University and embedded within existing curriculum. Descriptive statistical analysis was used to explore responses. Results: In total, 113 of 340 (33%) students completed the survey. Seventy-eight percent (n = 65) reported the eLearning would enable them to teach adults and children to swallow SODFs successfully. Learners either agreed or strongly agreed that they felt comfortable to teach patients (95%, n = 62/113) and parents or carers (94%, n = 60) to swallow medications having completed the e-learning. Student pharmacists generally found eLearning as an acceptable way to reflect on their own experiences of ‘pill’ swallowing and how to support patients to swallow SODFs. Conclusion: The KidzMed eLearning was well received by student pharmacists. Further work is needed to explore whether skills translates into real life application in the clinical settings

The Controversy Surrounding The Man Who Would Be Queen: A Case History of the Politics of Science, Identity, and Sex in the Internet Age

In 2003, psychology professor and sex researcher J. Michael Bailey published a book entitled The Man Who Would Be Queen: The Science of Gender-Bending and Transsexualism. The book’s portrayal of male-to-female (MTF) transsexualism, based on a theory developed by sexologist Ray Blanchard, outraged some transgender activists. They believed the book to be typical of much of the biomedical literature on transsexuality—oppressive in both tone and claims, insulting to their senses of self, and damaging to their public identities. Some saw the book as especially dangerous because it claimed to be based on rigorous science, was published by an imprint of the National Academy of Sciences, and argued that MTF sex changes are motivated primarily by erotic interests and not by the problem of having the gender identity common to one sex in the body of the other. Dissatisfied with the option of merely criticizing the book, a small number of transwomen (particularly Lynn Conway, Andrea James, and Deirdre McCloskey) worked to try to ruin Bailey. Using published and unpublished sources as well as original interviews, this essay traces the history of the backlash against Bailey and his book. It also provides a thorough exegesis of the book’s treatment of transsexuality and includes a comprehensive investigation of the merit of the charges made against Bailey that he had behaved unethically, immorally, and illegally in the production of his book. The essay closes with an epilogue that explores what has happened since 2003 to the central ideas and major players in the controversy

Mucosal Targeting of a BoNT/A Subunit Vaccine Adjuvanted with a Mast Cell Activator Enhances Induction of BoNT/A Neutralizing Antibodies in Rabbits

We previously reported that the immunogenicity of Hcβtre, a botulinum neurotoxin A (BoNT/A) immunogen, was enhanced by fusion to an epithelial cell binding domain, Ad2F, when nasally delivered to mice with cholera toxin (CT). This study was performed to determine if Ad2F would enhance the nasal immunogenicity of Hcβtre in rabbits, an animal model with a nasal cavity anatomy similar to humans. Since CT is not safe for human use, we also tested the adjuvant activity of compound 48/80 (C48/80), a mast cell activating compound previously determined to safely exhibit nasal adjuvant activity in mice.New Zealand White or Dutch Belted rabbits were nasally immunized with Hcβtre or Hcβtre-Ad2F alone or combined with CT or C48/80, and serum samples were tested for the presence of Hcβtre-specific binding (ELISA) or BoNT/A neutralizing antibodies.Hcβtre-Ad2F nasally administered with CT induced serum anti-Hcβtre IgG ELISA and BoNT/A neutralizing antibody titers greater than those induced by Hcβtre + CT. C48/80 provided significant nasal adjuvant activity and induced BoNT/A-neutralizing antibodies similar to those induced by CT.Ad2F enhanced the nasal immunogenicity of Hcβtre, and the mast cell activator C48/80 was an effective adjuvant for nasal immunization in rabbits, an animal model with a nasal cavity anatomy similar to that in humans

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Evolution of Antimicrobial Peptides to Self-Assembled Peptides for Biomaterial Applications

Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides harness a “bottom-up” approach, whereby the primary peptide sequence may be modified with natural and unnatural amino acids to produce an inherently antimicrobial hydrogel. Gelation may be tailored to occur in the presence of physiological and infective indicators (e.g. pH, enzymes) and therefore allow local, targeted antimicrobial therapy at the site of infection. Peptides demonstrate inherent biocompatibility, antimicrobial activity, biodegradability and numerous functional groups. They are therefore prime candidates for the production of polymeric molecules that have the potential to be conjugated to biomaterials with precision. Non-native chemistries and functional groups are easily incorporated into the peptide backbone allowing peptide hydrogels to be tailored to specific functional requirements. This article reviews an area of increasing interest, namely self-assembled peptides and their potential therapeutic applications as innovative hydrogels and biomaterials in the prevention of biofilm-related infection