Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation

Pd nanowire coatings of laser-treated polyethylene naphthalate: Preparation, characterization and biological response

Polymeric biomaterials treated by nanostructured metal coatings are very efficient against a wide spectrum of nosocomial pathogens. One of the most effective ways for the preparation of such metal/polymer composites is the combination of excimer laser modification of polymeric materials and vacuum evaporation of noble metals. By this way, we successfully prepared palladium nanowire arrays (PdNWs) supported on biocompatible polyethylene naphthalate (PEN). The characterization of prepared PdNWs on the surface of PEN was accomplished by various methods, such as X-ray Photoelectron Spectroscopy (XPS), Focussed Ion Beam Scanning Electron Microscopy (FIB-SEM), and Atomic Force Microscopy (AFM). PdNWs were preferentially formed from one side of underlying ripples. Pd release in antibacterial testing was measured by Inductively coupled plasma mass spectrometry (ICP-MS). Then, the antibacterial and cytotoxic effects were evaluated by (i) drop plate method using E. coli (G–) and S. epidermidis (G+ bacteria), and (ii) WST-1 cytotoxicity assay with three model cell lines (L929, NIH 3T3, RAW 264.7), respectively. Pd-treated samples exhibited significant antibacterial effects, increasing with cultivation time. Cytotoxicity assay showed that the absorbance of PEN/PdNWs samples was mildly decreased, suggesting considerably low cytotoxic effects of PdNWs

Evolution of the Synthesis of AMPK Activators for the Treatment of Diabetic Nephropathy: From Three Preclinical Candidates to the Investigational New Drug PF-06409577

Indole acids <b>1</b>, <b>2</b>, and <b>3</b> are potent 5′-adenosine monophosphate-activated protein kinase (AMPK) activators for the potential treatment of diabetic nephropathy. Compounds <b>1</b>–<b>3</b> were scaled to supply material for preclinical studies, and indole <b>3</b> was selected for advancement to first-in-human clinical trials and scaled to kilogram quantities. The progression of the synthesis strategy for these AMPK activators is described, as routes were selected for efficient structure–activity relationship generation and then improved for larger scales. The developed sequences employed practical isolations of intermediates and APIs, reproducible cross-coupling, hydrolysis, and other transformations, and enhanced safety and purity profiles and led to the production of 40–50 g of <b>1</b> and <b>2</b> and 2.4 kg of <b>3</b>. Multiple polymorphs of <b>3</b> were observed, and conditions for the reproducible formation of crystalline material suitable for clinical development were identified