Keypad mobile phones are associated with a significant increased risk of microbial contamination compared to touch screen phones

The use of mobile phones in the clinical environment by healthcare workers has become widespread. Despite evidence that these devices can harbour pathogenic micro-organisms there is little guidance on how to reduce contamination. Recently touchscreen phones with a single flat surface have been introduced. We hypothesise that bacterial contamination of phones used in hospitals will be lower on touchscreen devices compared to keypad devices. Sixty seven mobile phones belonging to health care workers were sampled. The median colony count for touchscreen phones and keypad devices was 0·09 colony forming units (cfu)/cm2 (interquartile range (IQR) 0.05–0·14) and 0·77 cfu/cm2 (IQR range 0·45–3.52) respectively. Colony counts were significantly higher on the keypad phones (Fisher’s exact test p<0.001). Multivariate analysis showed the type of phone (keypad vs. touch screen) was associated with increased colony counts (F-statistic 14.13: p<0.001). Overall, nine (13%) phones grew either meticillin resistant Staphylococcus aureus or vancomycin resistant enterococci. Eight (24%) keypad phones were contaminated with these organisms compared with one touch screen phone (3%). Our data indicate that touchscreen mobile phones are less contaminated than their keypad counterparts, and they are less likely to harbour pathogenic bacteria in the clinical setting

Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae

Extracytoplasmic solute receptors (ESRs) are important components of solute uptake systems in bacteria, having been studied extensively as parts of ATP binding cassette transporters. Herein we report the first crystal structure of an ESR protein from a functionally characterized electrochemical ion gradient-dependent secondary transporter. This protein, SiaP, forms part of a tripartite ATP-independent periplasmic transporter specific for sialic acid in Haemophilus influenzae. Surprisingly, the structure reveals an overall topology similar to ATP binding cassette ESR proteins, which is not apparent from the sequence, demonstrating that primary and secondary transporters can share a common structural component. The structure of SiaP in the presence of the sialic acid analogue 2,3-didehydro-2-deoxyN-acetylneuraminic acid reveals the ligand bound in a deep cavity with its carboxylate group forming a salt bridge with a highly conserved Arg residue. Sialic acid binding, which obeys simple bimolecular association kinetics as determined by stopped-flow fluorescence spectroscopy, is accompanied by domain closure about a hinge region and the kinking of an alpha-helix hinge component. The structure provides insight into the evolution, mechanism, and substrate specificity of ESR-dependent secondary transporters that are widespread in prokaryotes

Angiogenic gene signature in human pancreatic cancer correlates with TGF-beta and inflammatory transcriptomes

Pancreatic ductal adenocarcinomas (PDACs) are hypovascular, but overexpress pro-angiogenic factors and exhibit regions of microvasculature. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we previously reported that ~12% of PDACs have an angiogenesis gene signature with increased expression of multiple pro-angiogenic genes. By analyzing the recently expanded TCGA dataset, we now report that this signature is present in ~35% of PDACs but that it is mostly distinct from an angiogenesis signature present in pancreatic neuroendocrine tumors (PNETs). These PDACs exhibit a transcriptome that reflects active TGF-β signaling, and up-regulation of several pro-inflammatory genes, and many members of JAK signaling pathways. Moreover, expression of SMAD4 and HDAC9 correlates with endothelial cell abundance in PDAC tissues. Concomitantly targeting the TGF-β type I receptor (TβRI) kinase with SB505124 and JAK1-2 with ruxolitinib suppresses JAK1 phosphorylation and blocks proliferative cross-talk between human pancreatic cancer cells (PCCs) and human endothelial cells (ECs), and these anti-proliferative effects were mimicked by JAK1 silencing in ECs. By contrast, either inhibitor alone does not suppress their enhanced proliferation in 3D co-cultures. These findings suggest that targeting both TGF-β and JAK1 signaling could be explored therapeutically in the 35% of PDAC patients whose cancers exhibit an angiogenesis gene signature

Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study

Introduction: Identifying acute hypercapnic respiratory failure is crucial in the initial management of acute exacerbations of COPD. Guidelines recommend obtaining arterial blood samples but these are more difficult to obtain than venous. We assessed whether blood gas values derived from venous blood could replace arterial at initial assessment. Methods: Patients requiring hospital treatment for an exacerbation of COPD had paired arterial and venous samples taken. Bland–Altman analyses were performed to assess agreement between arterial and venous pH, CO2 and . The relationship between SpO2 and SaO2 was assessed. The number of attempts and pain scores for each sample were measured. Results: 234 patients were studied. There was good agreement between arterial and venous measures of pH and (mean difference 0.03 and −0.04, limits of agreement −0.05 to 0.11 and −2.90 to 2.82, respectively), and between SaO2 and SpO2 (in patients with an SpO2 of >80%). Arterial sampling required more attempts and was more painful than venous (mean pain score 4 (IQR 2–5) and 1 (IQR 0–2), respectively, p<0.001). Conclusions: Arterial sampling is more difficult and more painful than venous sampling. There is good agreement between pH and values derived from venous and arterial blood, and between pulse oximetry and arterial blood gas oxygen saturations. These agreements could allow the initial assessment of COPD exacerbations to be based on venous blood gas analysis and pulse oximetry, simplifying the care pathway and improving the patient experience

Multi-reflection polarimetry in microfluidics

The field of microfluidics promises new portable, low-cost sensing systems, as well as the capabilities to measure the physical or chemical properties of precious samples, for which only small volumes are available. However, when using microfluidic channels with millimeter to micron scale dimensions, together with optical sensing methods, these configurations result in short path lengths over which the signal can be acquired. Whilst polarimetry would greatly benefit from using small volumes, providing important information on the structure of chiral biomarkers in life sciences, the small interrogation volumes associated with the use of minute samples decreases the numbers of molecules in the light path that cause an optical rotation and reduces the sensitivity of the technique. Here, we show that when an optical beam, passing through a chiral sample, undergoes multiple reflections from suitably aligned external micromirrors, the usual cancelling out of the optical rotation, that occurs when the rotated polarized beam is passed back through a solution following reflection at a single mirror, can be negated. This enables the chirality of molecular species present in a microfluidic sample to be measured with increased sensitivity. This approach was validated experimentally using solutions of D-(+)-glucose as a model system, by investigating the effect of multiple reflections of a linearly polarized He-Ne laser beam and a 403 nm diode laser beam across the microfluidic channel. It was found that there was a 30-fold enhancement in the limit of detection with as few as 11 reflections through the sample

Inferred summer precipitation for southern Ontario back to AD 610, as reconstructed from ring widths of Thuja occidentalis

We present a network of seven ring-width chronologies of eastern white-cedar (Thuja occidentalis L.) from the Niagara Escarpment in southern Ontario, Canada. Using principal component regression, a 350-year June-July precipitation reconstruction (SOR) is developed for the region. Prior to the 20th century, the SOR series shows reasonable coherence, particularly at the decadal scale, with an independent tree-ring-based reconstruction of the Palmer drought severity index (PDSI) for roughly the same region. A weakening of the tree-growth – climate relationship in recent decades results in a regression model explaining 21% of the variance in the original climate series when the recent data are used for calibration. We therefore compromise with a model, calibrated for the period 1900–1960, which explains 33% of the variance. The model, while not terribly strong, does pass verification tests, indicating some degree of predictive skill. The longest chronology in our network, the 2787-year Flowerpot Island (FLOW) chronology, also exhibits common variability with the PDSI reconstruction, particularly on decadal and longer time scales and was used to infer hydroclimatic conditions back to AD 610. The combined information of the SOR, PDSI, and FLOW series suggests that dry conditions existed for the periods 1700–1725, 1750–1800, and 1840–1900, and wet conditions for the periods 1675–1700, 1730–1750, and 1810–1840. Over longer time scales, the FLOW chronology shows that summer precipitation was particularly variable during the 7th, 9th, 13th, and 16th centuries