A prospective window into medical device-related pressure ulcers in intensive care

Objective: To determine the prevalence, severity, location, etiology, treatment, and healing of medical device-related pressure ulcers in intensive care patients for up to 7 days. Design: Prospective repeated measures study. Setting and participants: Patients in 6 intensive care units of 2 major medical centers, one each in Australia and the United States, were screened 1 day per month for 6 months. Those with device-related ulcers were followed daily up to 7 days. Outcome measures: Device-related ulcer prevalence, pain, infection, treatment, healing. Results: 15/483 patients had device-related ulcers and 9/15 with 11 ulcers were followed beyond screening. Their mean age was 60.5 years, most were men, over-weight, and at increased pressure ulcer risk. Endotracheal and nasogastric tubes were the cause of most device-related ulcers. Repositioning was the most frequent treatment. 4/11 ulcers healed within the 7 day observation period. Conclusion: Device-related ulcer prevalence was 3.1%, similar to that reported in the limited literature available, indicating an ongoing problem. Systematic assessment and repositioning of devices are the mainstays of care. We recommend continued prevalence determination and that nurses remain vigilant to prevent device-related ulcers, especially in patients with nasogastric and endotracheal tubes.

An in-vitro 3-D cell culture model for studying pathomechanisms in AMD

Purpose To develop a novel 3-D cell culture model with the view to studying the pathomechanisms underlying the development of age-related macular degeneration (AMD). Our central hypothesis is that the silk structural protein fibroin used in conjunction with cultured human cells can be used to mimic the structural relationships between the RPE and choriocapillaris in health and disease. Methods Co-cultures of human RPE cells (ARPE-19 cells grown in Miller’s medium) and microvascular endothelial cells (HMEC-1 cells grown in endothelial culture medium) were established on opposing sides of a synthetic Bruch’s membrane (3 microns thick) constructed from B mori silk fibroin. Cell attachment was facilitated by pre-coating the fibroin membrane with vitronectin (for ARPE-19 cells) and gelatin (for HMEC-1 cells) respectively. The effects of tropoelastin on attachment of ARPE-19 cells was also examined. Barrier function was examined by measurement of trans-epithelial resistance (TER) using a voltohmmeter (EVOM-2). The phagocytic activity of the synthetic RPE was tested using vitronectin-coated microspheres (2 micron diameter FluoSpheres). In some cultures, membrane defects were created by puncturing within a 24 G needle. The architecture of the synthetic tissue before and after wounding was examined by confocal microscopy after staining for ZO-1 and F-actin. Results The RPE layer of the 3D model developed a cobblestoned morphology (validated by staining for ZO-1 and F-actin), displayed barrier function (validated by measurement of TER) and demonstrated cytoplasmic uptake of vitronectin-coated microspheres. Attachment of ARPE-19 cells to fibroin was unaffected by tropoelastin. Microvascular endothelial cells attached well to the gelatin-coated surface of the fibroin membrane and remained physically separated from the overlaying RPE layer. The fibroin membranes were amenable to puncturing without collapse thus providing the opportunity to study transmembrane migration of the endothelial cells. Conclusions Synthetic Bruch’s membranes constructed from silk fibroin, vitronectin and gelatin, support the co-cultivation of RPE cells and microvascular endothelial cells. The resulting RPE layer displays functions similar to that of native RPE and the entire tri-layered structure displays potential to be used as an in vitro model of choroidal neovascularization.

Temporal summation of intrinsically photosensitive retinal ganglion cell (ipRGC) contributions to the human pupil.

Purpose: IpRGCs mediate non-image forming functions including photoentrainment and the pupil light reflex (PLR). Temporal summation increases visual sensitivity and decreases temporal resolution for image forming vision, but the summation properties of nonimage forming vision are unknown. We investigated the temporal summation of inner (ipRGC) and outer (rod/cone) retinal inputs to the PLR. Method: The consensual PLR of the left eye was measured in six participants with normal vision using a Maxwellian view infrared pupillometer. Temporal summation was investigated using a double-pulse protocol (100 ms stimulus pairs; 0–1024 ms inter-stimulus interval, ISI) presented to the dilated fellow right eye (Tropicamide 1%). Stimulus lights (blue λmax = 460 nm; red λmax = 638 nm) biased activity to inneror outer retinal inputs to non-image forming vision. Temporal summation was measured suprathreshold (15.2 log photons.cm−2.s−1 at the cornea) and subthreshold (11.4 log photons.cm−2.s−1 at the cornea). Results: RM-ANOVAs showed the suprathreshold and subthreshold 6 second post illumination pupil response (PIPR: expressed as percentage baseline diameter) did not significantly vary for red or blue stimuli (p > .05). The PIPR for a subthreshold red 16 ms double-pulse control condition did not significantly differ with ISI (p > .05). The maximum constriction amplitude for red and blue 100 ms double- pulse stimuli did not significantly vary with ISI (p > .05). Conclusion: The non-significant changes in suprathreshold PIPR and subthreshold maximum pupil constriction indicate that inner retinal ipRGC inputs and outer retinal photoreceptor inputs to the PLR do not show temporal summation. The results suggest a fundamental difference between the temporal summation characteristics of image forming and non-image forming vision.

Effects of schedule pressure on construction performance

Accelerating a project can be rewarding. The consequences, however, can be troublesome if productivity and quality are sacrificed for the sake of remaining ahead of schedule, such that the actual schedule benefits are often barely worth the effort. The tradeoffs and paths of schedule pressure and its causes and effects are often overlooked when schedule decisions are being made. This paper analyses the effects that schedule pressure has on construction performance, and focuses on tradeoffs in scheduling. A research framework has been developed using a causal diagram to illustrate the cause-and-effect analysis of schedule pressure. An empirical investigation has been performed by using survey data collected from 102 construction practitioners working in 38 construction sites in Singapore. The results of this survey data analysis indicate that advantages of increasing the pace of work—by working under schedule pressure—can be offset by losses in productivity and quality. The negative effects of schedule pressure arise mainly by working out of sequence, generating work defects, cutting corners, and losing the motivation to work. The adverse effects of schedule pressure can be minimized by scheduling construction activities realistically and planning them proactively, motivating workers, and by establishing an effective project coordination and communication mechanism.

Combustion products of bulk aluminum rods burning in high pressure oxygen

Characterization of the combustion products released during the burning of commonly used engineering metallic materials may aid in material selection and risk assessment for the design of oxygen systems. The characterization of combustion products in regards to size distribution and morphology gives useful information for systems addressing fire detection. Aluminum rods (3.2-mm diameter cylinders) were vertically mounted inside a combustion chamber and ignited in pressurized oxygen by resistively heating an aluminum/palladium igniter wire attached to the bottom of the test sample. This paper describes the experimental work conducted to establish the particle size distribution and morphology of the resultant combustion products collected after the burning was completed and subsequently analyzed. In general, the combustion products consisted of a re-solidified oxidized slag and many small hollow spheres of size ranging from about 500 nm to 1000 µm in diameter, surfaced with quenched dendritic and grain-like structures. The combustion products were characterized using optical and scanning electron microscopy.

Inter-cycle variability of in-cylinder pressure parameters in an ethanol fumigated common rail diesel engine

The effects of ethanol fumigation on the inter-cycle variability of key in-cylinder pressure parameters in a modern common rail diesel engine have been investigated. Specifically, maximum rate of pressure rise, peak pressure, peak pressure timing and ignition delay were investigated. A new methodology for investigating the start of combustion was also proposed and demonstrated—which is particularly useful with noisy in-cylinder pressure data as it can have a significant effect on the calculation of an accurate net rate of heat release indicator diagram. Inter-cycle variability has been traditionally investigated using the coefficient of variation. However, deeper insight into engine operation is given by presenting the results as kernel density estimates; hence, allowing investigation of otherwise unnoticed phenomena, including: multi-modal and skewed behaviour. This study has found that operation of a common rail diesel engine with high ethanol substitutions (>20% at full load, >30% at three quarter load) results in a significant reduction in ignition delay. Further, this study also concluded that if the engine is operated with absolute air to fuel ratios (mole basis) less than 80, the inter-cycle variability is substantially increased compared to normal operation.

Cell death control : the interplay of apoptosis and autophagy in the pathogenicity of sclerotinia sclerotiorum

Programmed cell death is characterized by a cascade of tightly controlled events that culminate in the orchestrated death of the cell. In multicellular organisms autophagy and apoptosis are recognized as two principal means by which these genetically determined cell deaths occur. During plant-microbe interactions cell death programs can mediate both resistant and susceptible events. Via oxalic acid (OA), the necrotrophic phytopathogen Sclerotinia sclerotiorum hijacks host pathways and induces cell death in host plant tissue resulting in hallmark apoptotic features in a time and dose dependent manner. OA-deficient mutants are non-pathogenic and trigger a restricted cell death phenotype in the host that unexpectedly exhibits markers associated with the plant hypersensitive response including callose deposition and a pronounced oxidative burst, suggesting the plant can recognize and in this case respond, defensively. The details of this plant directed restrictive cell death associated with OA deficient mutants is the focus of this work. Using a combination of electron and fluorescence microscopy, chemical effectors and reverse genetics, we show that this restricted cell death is autophagic. Inhibition of autophagy rescued the non-pathogenic mutant phenotype. These findings indicate that autophagy is a defense response in this necrotrophic fungus/plant interaction and suggest a novel function associated with OA; namely, the suppression of autophagy. These data suggest that not all cell deaths are equivalent, and though programmed cell death occurs in both situations, the outcome is predicated on who is in control of the cell death machinery. Based on our data, we suggest that it is not cell death per se that dictates the outcome of certain plant-microbe interactions, but the manner by which cell death occurs that is crucial.

Pressure ulcers in the adult intensive care unit : a literature review of patient risk factors and risk assessment scales

Background: Critically ill patients are at high risk for pressure ulcer (PrU) development due to their high acuity and the invasive nature of the multiple interventions and therapies they receive. With reported incidence rates of PrU development in the adult critical care population as high as 56%, the identification of patients at high risk of PrU development is essential. This paper will explore the association between PrU development and risk factors. It will also explore PrU development and the use of risk assessment scales for critically ill patients in adult intensive care units. Method: A literature search from 2000 to 2012 using the CINHAL, Cochrane Library, EBSCOHost, Medline (via EBSCOHost), PubMed, ProQuest and Google Scholar databases was conducted. Key words used were: pressure ulcer/s; pressure sore/s; decubitus ulcer/s; bed sore/s; critical care; intensive care; critical illness; prevalence; incidence; prevention; management; risk factor; risk assessment scale. Results: Nineteen articles were included in this review; eight studies addressing PrU risk factors, eight studies addressing risk assessment scales and three studies overlapping both. Results from the studies reviewed identified 28 intrinsic and extrinsic risk factors which may lead to PrU development. Development of a risk factor prediction model in this patient population, although beneficial, appears problematic due to many issues such as diverse diagnoses and subsequent patient needs. Additionally, several risk assessment instruments have been developed for early screening of patients at higher risk of developing PrU in the ICU. No existing risk assessment scales are valid for identification high risk critically ill patient,with the majority of scales potentially over-predicting patients at risk for PrU development. Conclusion: Research studies to inform the risk factors for potential pressure ulcer development are inconsistent. Additionally, there is no consistent or clear evidence which demonstrates any scale to better or more effective than another when used to identify the patients at risk for PrU development. Furthermore robust research is needed to identify the risk factors and develop valid scales for measuring the risk of PrU development in ICU.

Travelling waves for a velocity–jump model of cell migration and proliferation

Cell invasion, characterised by moving fronts of cells, is an essential aspect of development, repair and disease. Typically, mathematical models of cell invasion are based on the Fisher–Kolmogorov equation. These traditional parabolic models can not be used to represent experimental measurements of individual cell velocities within the invading population since they imply that information propagates with infinite speed. To overcome this limitation we study combined cell motility and proliferation based on a velocity–jump process where information propagates with finite speed. The model treats the total population of cells as two interacting subpopulations: a subpopulation of left–moving cells, $L(x,t)$, and a subpopulation of right–moving cells, $R(x,t)$. This leads to a system of hyperbolic partial differential equations that includes a turning rate, $\Lambda \ge 0$, describing the rate at which individuals in the population change direction of movement. We present exact travelling wave solutions of the system of partial differential equations for the special case where $\Lambda = 0$ and in the limit that $\Lambda \to \infty$. For intermediate turning rates, $0 < \Lambda < \infty$, we analyse the travelling waves using the phase plane and we demonstrate a transition from smooth monotone travelling waves to smooth nonmonotone travelling waves as $\Lambda$ decreases through a critical value $\Lambda_{crit}$. We conclude by providing a qualitative comparison between the travelling wave solutions of our model and experimental observations of cell invasion. This comparison indicates that the small $\Lambda$ limit produces results that are consistent with experimental observations.

An accurate numerical scheme for the contraction of a bubble in a Hele-Shaw cell

We report on an accurate numerical scheme for the evolution of an inviscid bubble in radial Hele-Shaw flow, where the nonlinear boundary effects of surface tension and kinetic undercooling are included on the bubble-fluid interface. As well as demonstrating the onset of the Saffman-Taylor instability for growing bubbles, the numerical method is used to show the effect of the boundary conditions on the separation (pinch-off) of a contracting bubble into multiple bubbles, and the existence of multiple possible asymptotic bubble shapes in the extinction limit. The numerical scheme also allows for the accurate computation of bubbles which pinch off very close to the theoretical extinction time, raising the possibility of computing solutions for the evolution of bubbles with non-generic extinction behaviour.

Sensitivity of edge detection methods for quantifying cell migration assays

Quantitative imaging methods to analyze cell migration assays are not standardized. Here we present a suite of two–dimensional barrier assays describing the collective spreading of an initially–confined population of 3T3 fibroblast cells. To quantify the motility rate we apply two different automatic image detection methods to locate the position of the leading edge of the spreading population after 24, 48 and 72 hours. These results are compared with a manual edge detection method where we systematically vary the detection threshold. Our results indicate that the observed spreading rates are very sensitive to the choice of image analysis tools and we show that a standard measure of cell migration can vary by as much as 25% for the same experimental images depending on the details of the image analysis tools. Our results imply that it is very difficult, if not impossible, to meaningfully compare previously published measures of cell migration since previous results have been obtained using different image analysis techniques and the details of these techniques are not always reported. Using a mathematical model, we provide a physical interpretation of our edge detection results. The physical interpretation is important since edge detection algorithms alone do not specify any physical measure, or physical definition, of the leading edge of the spreading population. Our modeling indicates that variations in the image threshold parameter correspond to a consistent variation in the local cell density. This means that varying the threshold parameter is equivalent to varying the location of the leading edge in the range of approximately 1–5% of the maximum cell density.

SECIS-binding protein 2 promotes cell survival by protecting against oxidative stress

Reactive oxygen species (ROS) are a primary cause of cellular damage that leads to cell death. In cells, protection from ROS-induced damage and maintenance of the redox balance is mediated to a large extent by selenoproteins, a distinct family of proteins that contain selenium in form of selenocysteine (Sec) within their active site. Incorporation of Sec requires the Sec-insertion sequence element (SECIS) in the 3'-untranslated region of selenoproteins mRNAs and the SECIS-binding protein 2 (SBP2). Previous studies have shown that SBP2 is required for the Sec-incorporation mechanism; however, additional roles of SBP2 in the cell have remained undefined. We herein show that depletion of SBP2 by using antisense oligonucleotides (ASOs) causes oxidative stress and induction of caspase- and cytochrome c-dependent apoptosis. Cells depleted of SBP2 have increased levels of ROS, which lead to cellular stress manifested as 8-oxo-7,8-dihydroguanine (8-oxo-dG) DNA lesions, stress granules, and lipid peroxidation. Small-molecule antioxidants N-acetylcysteine, glutathione, and α-tocopherol only marginally reduced ROS and were unable to rescue cells fully from apoptosis, indicating that apoptosis might be directly mediated by selenoproteins. Our results demonstrate that SBP2 is required for protection against ROS-induced cellular damage and cell survival. Antioxid. Redox Signal. 12, 797–808.

Incorporation of exogenous RGD peptide and inter-species blending as strategies for enhancing human corneal limbal epithelial cell growth on Bombyx mori silk fibroin membranes

While fibroin isolated from the cocoons of domesticated silkworm Bombyx mori supports growth of human corneal limbal epithelial (HLE) cells, the mechanism of cell attachment remains unclear. In the present study we sought to enhance the attachment of HLE cells to membranes of Bombyx mori silk fibroin (BMSF) through surface functionalization with an arginine-glycine-aspartic acid (RGD)-containing peptide. Moreover, we have examined the response of HLE cells to BMSF when blended with the fibroin produced by a wild silkworm, Antheraea pernyi, which is known to contain RGD sequences within its primary structure. A procedure to isolate A. pernyi silk fibroin (APSF) from the cocoons was established, and blends of the two fibroins were prepared at five different BMSF/APSF ratios. In another experiment, BMSF surface was modified by binding chemically the GRGDSPC peptide using a water-soluble carbodiimide. Primary HLE were grown in the absence of serum on membranes made of BMSF, APSF, and their blends, as well as on RGD-modified BMSF. There was no statistically significant enhancing effect on the cell attachment due to the RGD presence. This suggests that the adhesion through RGD ligands may have a complex mechanism, and the investigated strategies are of limited value unless the factors contributing to this mechanism become better known.