RNase 7 Contributes to the Cutaneous Defense against Enterococcus faecium

Background: Human skin is able to mount a fast response against invading microorganisms by the release of antimicrobial proteins such as the ribonuclease RNase 7. Because RNase 7 exhibits high activity against Enterococcus faecium the aim of this study was to further explore the role of RNase 7 in the cutaneous innate defense system against E. faecium. Methodology/Principal Findings: Absolute quantification using real-time PCR and ELISA revealed that primary keratinocytes expressed high levels of RNase 7. Immunohistochemistry showed RNase 7 expression in all epidermal layers of the skin with an intensification in the upper more differentiated layers. Furthermore, RNase 7 was secreted by keratinocytes in vitro and in vivo in a site-dependent way. RNase 7 was still active against E. faecium at low pH (5.5) or high NaCl (150 mM) concentration and the bactericidal activity of RNase 7 against E. faecium required no ribonuclease activity as shown by recombinant RNase 7 lacking enzymatic activity. To further explore the role of RNase 7 in cutaneous defense against E. faecium, we investigated whether RNase 7 contributes to the E. faecium killing activity of skin extracts derived from stratum corneum. Treatment of the skin extract with an RNase 7 specific antibody, which neutralizes the antimicrobial activity of RNase 7, diminished its E. faecium killing activity. Conclusions/Significance: Our data indicate that RNase 7 contributes to the E. faecium-killing activity of skin extracts an

Continuous glucose monitoring: Using cgm to guide insulin therapy virtual trials results

Continuous glucose monitoring (CGM) devices can measure blood glucose levels through interstitial measurements almost continuously (1-5min sampling period). However, they are not as accurate as glucose readings from blood measurements. The relation between tissue and blood glucose is dynamic and the sensor signal can degrade over time. In addition, CGM readings contains high frequency noise and can drift between measurements. However, maintaining continuous glucose monitoring has the potential to improve the level of glycemic control achieved and reduce nurse workload. For this purpose, a simple model was designed and tested to see the effect of inherent CGM error on the insulin therapy protocol, STAR (Stochastic TARgeted). An error model was generated from 9 patients that had one Guardian Real-Time CGM device (Medtronic Minimed, Northridge, CA, USA) inserted into their abdomen as part of an observation trial assesing the accuracy of CGM measurements compared to a blood gas analyser and glucometer readings. A resulting error model was then used to simulate the outcomes if the STAR protocol was guided by CGM values on 183 virtual patients. CGM alarms for hyper- and hypo-glycaemic region were included to improve patient safety acting as 'guardrails'. The STAR CGM protocol gave good performance and reduced workload by ∼50%, reducing the number of measurements per day per patient from 13 to 7. The number of hypoglycaemic events increased compared to the current STAR from 0.03% <2.2mmol/L to 0.32%. However, in comparison to other published protocols it is still a very low level of hypoglycaemia and less than clinically acceptable value of 5% <4.0mmol/L. More importantly this study shows great promise for the future of CGM and their use in clinic. With the a newer generation of sensors, specifically designed for the ICU, promising less noise and drift suggesting that a reduced nurse workload without compromising safety or performance is with in reach.? © 2015, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture