Size, shape and surface chemistry of nano-gold dictate its cellular interactions, uptake and toxicity

Colloidal gold is undoubtedly one of the most extensively studied nanomaterials, with 1000s of different protocols currently available to synthesise gold nanoparticles (AuNPs). While developments in the synthesis of AuNPs have progressed rapidly in recent years, our understanding of their biological impact, with particular respect to the effect of shape, size, surface characteristics and aggregation states, has struggled to keep pace. It is generally agreed that when AuNPs are exposed to biological systems, these parameters directly influence their pharmacokinetic and pharmacodynamic properties by influencing AuNPs distribution, circulation time, metabolism and excretion in biological systems. However, the rules governing these properties, and the science behind them, are poorly understood. Therefore, a systematic understanding of the implications of these variables at the nano-bio interface has recently become a topic of major interest. This Review Article attempts to ignite a discussion around the influence of different physico-chemical parameters on biological activity of AuNPs, while focussing on critical aspects of cellular interactions, uptake and cytotoxicity. The review also discusses emerging trends in AuNP uptake and toxicity that are leading to technological advances through AuNP-based therapy, diagnostics and imaging

TAS2R38 is a novel modifer gene in patients with cystic fbrosis

The clinical manifestation of cystic fbrosis (CF) is heterogeneous also in patients with the same cystic fbrosis transmembrane regulator (CFTR) genotype and in afected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was signifcantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifer gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF

Enantiomerically pure phosphonated carbocyclic 2'-oxa-3'-azanucleosides: synthesis and biological evaluation

Starting from enantiomeric pure 1-[(3S,5R)- and 1-[(3R,5S)-3-(hydroxymethyl)-2-methylisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-diones (-)7a and (+)7b, obtained by lipase-catalyzed resolution, pure diethyl{[(3S,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (-)12a and diethyl{[(3R,5S)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (+)12b have been synthesized. The obtained compounds showed no cytotoxic activity versus the U937 cell line in comparison with AZT, and were poorly able to inhibit HIV infection in vitro

Acute disseminated encephalomyelitis onset : evaluation based on vaccine adverse events reporting systems

OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM) by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) database and the EudraVigilance post-authorisation module (EVPM) were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40\ub121.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reactio

Improving electrocoagulation floatation for harvesting microalgae

Electro-coagulation floatation (ECF) is a foam-floatation dewatering method that has been shown to be a highly effective, rapid, and scalable separation methodology. In this manuscript, an in-depth analysis of the gas and flocculant levels observed during the process is provided, with microbubbles observed in the 5–80μm size range at a concentration of 102–103 bubbles mL−1. Electrolysis of microalgae culture was then observed, demonstrating both effective separation using aluminium electrodes (nine microalgal species tested, 1–40μm size range, motile and non-motile, marine and freshwater), and sterilisation of culture through bleaching with inert titanium electrodes. Atomic force microscopy was used to visualise floc formation in the presence and absence of algae, showing nanoscale structures on the magnitude of 40–400nm and entrapped microalgal cells. Improvements to aid industrial biotechnology processing were investigated: protein-doping was found to improve foam stability without inducing cell lysis, and an oxalate buffer wash regime was found to dissolve the flocculant whilst producing no observable difference in the final algal lipid or pigment profiles, leaving the cells viable at the end of the process. ECF separated microalgal culture had an algal biomass loading of 13% and as such wasideal for direct down-stream processing through hydrothermal liquefaction. Highbio-crude yieldswere achieved, though this was reduced slightly on addition of the Al(OH)3 after ECF, with carbon being distributed away to the aqueous and solid residue phases. The amenability and compatibility of ECF to integration with, or replacement of, existing centrifugation and settling processes suggests this process may be of significant interest to the biotechnology industry

Future business and the role of purchasing and supply management: Opportunities for ‘business-not-as-usual’ PSM research

The raison d'être for this article is simple: traditional ways of researching, theorizing, and practicing purchasing and supply management (PSM) are no longer sufficient to ‘meet the moment’. Scholars need to advance a “business-not-as-usual” footing approach to their work, if they are to make a meaningful contribution to addressing the current and future emergencies, as highlighted by recent extreme weather and the COVID-19 pandemic. Yet, what can this, or should this, mean for a field rooted in traditional business thinking? This article builds on the Journal of Purchasing and Supply Management's (JPSM) 25th Anniversary Special Issue editorial (2019); members of the JPSM's editorial team advance their unique perspectives on what “business-not-as-usual” means for PSM. Specifically, we advocate both thinking much more widely, in scope and ambition, than we currently do, and simultaneously building our ability to comprehend supply chains in a more nuanced and granular way. We explore whether the bias toward positivist work has omitted potentially interesting findings, and viewpoints. This leads to a call to re-think how we approach our work: should the key criteria always be to focus on theory development or testing? Should academics “think bigger”? Turning to specific research themes, illustrations of how our current thinking can be challenged or broadened by addressing the circular economy, and role of purchasing and innovation. Specifically, the focus on the PSM function as an intrapreneur within the larger organization, and the role of innovation and technology in PSM work. Taken together, we hope the ideas and arguments presented here will inform and inspire ambitious and novel approaches to PSM research with significant and enduring impact on the transformation of business

No signal of interactions between influenza vaccines and drugs used for chronic diseases : a case-by-case analysis of the vaccine adverse event reporting system and vigibase

Background: An increasing number of reports indicates that vaccines against influenza may interact with specific drugs via drug metabolism. To date, actual impact of vaccine-drug interactions observed in the real world clinical practice has not been investigated.Methods: From VAERS and VigiBase, we collected Adverse Event Following Immunization (AEFI) reports for individuals receiving vaccines against influenza recorded as suspect and selected cases where predictable toxicity was recorded with oral anticoagulants, antiepileptics and statins (i.e. hemorrhages, overdosage and rhabdomyolysis, respectively). We applied AEFI and Drug Interaction Probability Scale (DIPS) Algorithms to assess causality of drug-vaccine interactions.Results: 116 AEFI reports submitted to VAERS and 83 from Vigibase were included in our analysis; antiepileptics and statins were related to the highest number of indeterminate/consistent (93.7%; 65.3%) and possible/probable (50%; 57.7%) cases according to the AEFI and DIPS, respectively. The majority of cases occurred within the first week after vaccine administration (5-7days).Conclusion: The relative paucity of detected interactions does not impact on the benefit of the vaccination against influenza, which remains strongly recommended; this does not exclude that closer monitoring for selected patients exposed to concomitant chronic pharmacological therapies and affected by predisposing factors may be useful