Imaging of Mechanically Induced Thermal Heat Patterns

Imaging information obtained from nondestructive tests is becoming more widely investigated and developed. Imaging obviously has the potential to provide a more easily interpreted outcome of a nondestructive test, leading to more rapid and correct evaluation of the state of the examined material. This work presents one aspect of the field of imaging — developing a thermal image of the surface of a material subjected to mechanical vibrations. The technique of vibrothermography has been under investigation in our laboratory for several years, especially as applied to advanced composite materials. We will present in this paper a review of the imaging aspects of the technique, in particular discussing the phenomena responsible for producing a surface heat pattern and the phenomena responsible for obtaining a suitable image of this pattern. Finally, a discussion is given of the possible interpretations which may be made from the image concerning evaluation of the material condition, as may be used in a nondestructive evaluation procedure. Examples will be drawn from a number of tests performed in our laboratory

Hand hygiene compliance monitoring in anaesthetics: Feasibility and validity

Background: Hand hygiene compliance scores in the anaesthetic department of an acute NHS hospital were persistently low. Aims: To determine the feasibility and validity of regular accurate measurement of HHC in anaesthetics and understand the context of care delivery, barriers and opportunities to improve compliance. Methods: The hand hygiene compliance of one anaesthetist was observed and noted by a senior infection control practitioner (ICP). This was compared to the World Health Organization five moments of hand hygiene and the organisation hand hygiene tool. Findings: In one sequence of 55 min, there were approximately 58 hand hygiene opportunities. The hand hygiene compliance rate was 16%. The frequency and speed of actions in certain periods of care delivery made compliance measurement difficult and potentially unreliable. During several activities, taking time to apply alcohol gel or wash hands would have put the patients at significant risk. Discussion: We concluded that hand hygiene compliance monitoring by direct observation was invalid and unreliable in this specialty. It is important that hand hygiene compliance is optimal in anaesthetics particularly before patient contact. Interventions which reduce environmental and patient contamination, such as cleaning the patient and environment, could ensure anaesthetists encounter fewer micro-organisms in this specialty

Ex Vivo treatment of coronary artery endothelial cells with serum post-exercise training offers limited protection against in vitro exposure to FEC-T chemotherapy

Background: Chemotherapy treatment for breast cancer associates with well-documented cardiovascular detriments. Exercise has shown promise as a potentially protective intervention against cardiac toxicity. However, there is a paucity of evidence for the benefits of exercise on the vasculature. Objectives: This study aimed to determine the effects of chemotherapy on the vascular endothelium; and if there are protective effects of serological alterations elicited by an exercise training intervention. Methods and Results: 15 women participated in a 12-week home-based exercise intervention consisting of three high-intensity interval sessions per week. Human coronary artery endothelial cells (HCAEC) were exposed to physiological concentrations of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and docetaxel to determine a dose-response. Twenty-4 hours prior to FEC and docetaxel exposure, HCAECs were preconditioned with serum collected pre- and post-training. Annexin V binding and cleaved caspase-3 were assessed using flow cytometry and wound repair by scratch assays. Chemotherapy exposure increased HCAEC Annexin V binding, cleaved caspase-3 expression in a dose-dependent manner; and inhibited wound repair. Compared to pre-training serum, conditioning HCAECs with post-training serum, reduced Annexin V binding (42% vs. 30%, p = 0.01) when exposed to FEC. For docetaxel, there were no within-group differences (pre-vs post-exercise) for Annexin V binding or cleaved caspase-3 expression. There was a protective effect of post-training serum on wound repair for 5-flurouracil (p = 0.03) only. Conclusion: FEC-T chemotherapy drugs cause significant damage and dysfunction of endothelial cells. Preconditioning with serum collected after an exercise training intervention, elicited some protection against the usual toxicity of FEC-T, when compared to control serum

Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei.

AZD6738 is an orally active ATR inhibitor (ATRi) currently in phase I clinical trials. We found in vitro growth inhibitory activity of this ATRi in a panel of human cancer cell lines. We demonstrated radiosensitization by AZD6738 to single radiation fractions in multiple cancer cell lines independent of both p53 and BRCA2 status by the clonogenic assay. Radiosensitization by AZD6738 to clinically relevant doses of fractionated radiation was demonstrated in vitro using a 3D tumor spheroid model and, in vivo, AZD6738 radiosensitized by abrogating the radiation-induced G2 cell-cycle checkpoint and inhibiting homologous recombination. Mitosis with damaged DNA resulted in mitotic catastrophe as measured by micronucleus formation by live-cell fluorescent-ubiquitination cell-cycle imaging of cell-cycle progression and nuclear morphology. Induction of micronuclei was significantly more prominent for AZD6738 compared with inhibition of the downstream kinase CHK1 alone at isoeffective doses. Micronuclei were characterized as acentric chromosomal fragments, which displayed characteristics of increased DNA damage and cell-cycle dyssynchrony when compared with the primary nucleus. Mol Cancer Ther; 16(1); 25-34. ©2016 AACR

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

BACKGROUND: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. METHODS AND FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. CONCLUSIONS: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions

HSP90 inhibition sensitizes head and neck cancer to platin-based chemoradiotherapy by modulation of the DNA damage response resulting in chromosomal fragmentation.

Background Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922, combined with CCRT.Methods The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay. Modulation of the CCRT induced DNA damage response (DDR) by AUY922 was characterized by confocal image analysis of RAD51, BRCA1, 53BP1, ATM and mutant p53 signaling. The role of FANCA depletion by AUY922 was examined using shRNA. Cell cycle checkpoint abrogation and chromosomal fragmentation was assessed by western blot, FACS and confocal. The role of ATM was also assessed by shRNA. AUY922 in combination with CCRT was assessed in vivo.Results The combination of AUY922 with cisplatin, radiation and CCRT was found to be synergistic in p53 mutant HNSCC. AUY922 leads to significant alterations to the DDR induced by CCRT. This comprises inhibition of homologous recombination through decreased RAD51 and pS1524 BRCA1 with a corresponding increase in 53BP1 foci, activation of ATM and signaling into mutant p53. A shift to more error prone repair combined with a loss of checkpoint function leads to fragmentation of chromosomal material. The degree of disruption to DDR signalling correlated to chromosomal fragmentation and loss of clonogenicity. ATM shRNA indicated a possible rationale for the combination of AUY922 and CCRT in cells lacking ATM function.Conclusions This study supports future clinical studies combining AUY922 and CCRT in p53 mutant HNSCC. Modulation of the DDR and chromosomal fragmentation are likely to be analytical points of interest in such trials

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Anaesthetic considerations of adults with Morquio's syndrome - a case report

<p>Abstract</p> <p>Background</p> <p>The anaesthetic management of patients with Morquio syndrome is complicated by a number of factors including odontoid hypoplasia, atlantoaxial instability, thoracic kyphosis, and deposition of mucopolysaccharides in the soft tissue of the oropharnyx.</p> <p>Case presentation</p> <p>Herein we describe the anaesthetic considerations and management of a 26 year old adult with Morquio syndrome, who presented for an elective hip replacement.</p> <p>Conclusion</p> <p>This report details an awake fiberoptic intubation in an adult with Morquio syndrome. We recommend that this approach be considered in patients with Morquio syndrome undergoing general anaesthesia.</p

A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis

Invasion through the extracellular matrix (ECM) is important for wound healing, immunological responses and metastasis. We established an invasion-based cell motility screen using Boyden chambers overlaid with Matrigel to select for pro-invasive genes. By this method we identified antisense to MARCKS related protein (MRP), whose family member MARCKS is a target of miR-21, a microRNA involved in tumor growth, invasion and metastasis in multiple human cancers. We confirmed that targeted knockdown of MRP, in both EpRas mammary epithelial cells and PC3 prostate cancer cells, promoted in vitro cell migration that was blocked by trifluoperazine. Additionally, we observed increased immunofluoresence of E-cadherin, β-catenin and APC at sites of cell-cell contact in EpRas cells with MRP knockdown suggesting formation of adherens junctions. By wound healing assay we observed that reduced MRP supported collective cell migration, a type of cell movement where adherens junctions are maintained. However, destabilized adherens junctions, like those seen in EpRas cells, are frequently important for oncogenic signaling. Consequently, knockdown of MRP in EpRas caused loss of tumorigenesis in vivo, and reduced Wnt3a induced TCF reporter signaling in vitro. Together our data suggest that reducing MRP expression promotes formation of adherens junctions in EpRas cells, allowing collective cell migration, but interferes with oncogenic β-catenin signaling and tumorigenesis