Peristomal Skin Complications Are Common, Expensive, and Difficult to Manage: A Population Based Cost Modeling Study

BACKGROUND: Peristomal skin complications (PSCs) are the most common post-operative complications following creation of a stoma. Living with a stoma is a challenge, not only for the patient and their carers, but also for society as a whole. Due to methodological problems of PSC assessment, the associated health-economic burden of medium to longterm complications has been poorly described. AIM: The aim of the present study was to create a model to estimate treatment costs of PSCs using the standardized assessment Ostomy Skin Tool as a reference. The resultant model was applied to a real-life global data set of stoma patients (n = 3017) to determine the prevalence and financial burden of PSCs. METHODS: Eleven experienced stoma care nurses were interviewed to get a global understanding of a treatment algorithm that formed the basis of the cost analysis. The estimated costs were based on a seven week treatment period. PSC costs were estimated for five underlying diagnostic categories and three levels of severity. The estimated treatment costs of severe cases of PSCs were increased 2-5 fold for the different diagnostic categories of PSCs compared with mild cases. French unit costs were applied to the global data set. RESULTS: The estimated total average cost for a seven week treatment period (including appliances and accessories) was 263€ for those with PSCs (n = 1742) compared to 215€ for those without PSCs (n = 1172). A co-variance analysis showed that leakage level had a significant impact on PSC cost from 'rarely/never' to 'always/often' p<0.00001 and from 'rarely/never' to 'sometimes' p = 0.0115. CONCLUSION: PSCs are common and troublesome and the consequences are substantial, both for the patient and from a health economic viewpoint. PSCs should be diagnosed and treated at an early stage to prevent long term, debilitating and expensive complications

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia

Aims Arachidonic acid (AA) and its metabolites, prostaglandins (PG) are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV) remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs). Methods and Results We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM) and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM), an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV. Conclusion Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca2+ channels

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

The Use of a Disclosing Agent During Resective Periodontal Surgery for Improved Removal of Biofilm

A total removal of the bacterial deposits is one of the main challenges of periodontal therapy. A surgical approach is sometimes required in order to allow a correct access to the areas not thoroughly reached during the initial therapy. The present study focuses on the surgical scaling effectiveness in root deposits removal; the potential support of a disclosing agent during this procedure is also evaluated. Forty surgical periodontal patients were randomly divided between surgeries where the operator was informed about a final examination of the residual root deposits and surgeries where the operator was not informed. Straight after scaling procedures a supervisor recorded the O’Leary Plaque Index of the exposed roots by mean of a disclosing agent and the percentage of teeth with residual biofilm. After the stained deposits removal, a second chromatic examination was performed and new data were collected. Mann-Whitney U-test and Wilcoxon test for paired samples were used for comparisons respectively between the two surgery groups and the first and the second chromatic examination; one-sided p-value was set at 0.05. At first examination no significant differences between the two groups were observed regarding Plaque Index (p=0.24) and percentages of teeth with residual biofilm (p=0.07). The 100% removal of roots deposits was never achieved during the study but a significant reduction of 80% of root deposits was observed between first and second examination (p=0.0001). Since root deposits removal during periodontal surgery resulted always suboptimal, the use of a disclosing agent during this procedure could be a useful and practical aid

Fatigue strength of common tibial intramedullary nail distal locking screws

Premature failure of either the nail and/or locking screws with unstable fracture patterns may lead to angulation, shortening, malunion, and IM nail migration. Up to thirty percent of all unreamed nail locking screws can break after initial weight bearing is allowed at 8–10 weeks if union has not occurred. The primary problem this presents is hardware removal during revision surgery. The purposes of our study was to evaluate the relative fatigue resistance of distal locking screws and bolts from representative manufacturers of tibial IM nail systems, and develop a relative risk assessment of screws and materials used. Evaluations included quantitative and qualitative measures of the relative performance of these screws

The Relationship Between Bleeding on Probing and Subgingival Deposits. An Endoscopical Evaluation

none4Background: Bleeding on probing (BOP) is an indicator of tissue inflammatory response to bacterial pathogens. Because anatomical limitations the entity and physical state of microbial aggregations located under the gingival margin and their relations to BOP have been hardly investigated till now. The recent introduction of the endoscopy has allowed clinicians to view the subgingival environment in a non-traumatic way. Aim of this study is to evaluate the correlation between BOP and subgingival deposits by using this new technology. Methods: At one-month revaluation of 16 periodontal patients treated with scaling and root planning, 107 teeth (642 individual sites) were evaluated for plaque index (PI), gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP), endoscopic biofilm index (EBI) and endoscopic calculus index (ECI). Results: A linear association between BOP and PD, EBI, and ECI was detected. The BOP provided a high level of specificity but quite low sensitivity values both for ECI (sensitivity 40%, specificity 86%) and EBI (sensitivity 37%, specificity 89%). The BOP sensitivity was directly linked to the amount of subgingival deposits. Conclusions: This study demonstrates a direct relationship between BOP and presence/amount of subgingival deposits. More investigations on larger samples are however needed.noneChecchi l.; Montevecchi M.; Checchi V.; Zappulla F.Checchi l.; Montevecchi M.; Checchi V.; Zappulla F

An atlas of seabed biodiversity for Aotearoa New Zealand

\ua9 2023 Copernicus GmbH. All rights reserved. The waters of Aotearoa New Zealand span over 4.2ĝ€\uafmillionĝ€\uafkm2 of the South Pacific Ocean and harbour a rich diversity of seafloor-Associated taxa. Due to the immensity and remoteness of the area, there are significant gaps in the availability of data that can be used to quantify and map the distribution of seafloor and demersal biodiversity, limiting effective management. In this study, we describe the development and accessibility of an online atlas of seabed biodiversity that aims to fill these gaps. Species distribution models were developed for 579 taxa across four taxonomic groups: demersal fish, reef fish, subtidal invertebrates and macroalgae. Spatial layers for taxa distribution based on habitat suitability were statistically validated and then, as a further check, evaluated by taxonomic experts to provide measures of confidence to guide the future use of these layers. Spatially explicit uncertainty (SD) layers were also developed for each taxon distribution. We generated layer-specific metadata, including statistical and expert evaluation scores, which were uploaded alongside the accompanying spatial layers to the open access database Zenodo. This database provides the most comprehensive source of information on the distribution of seafloor taxa for Aotearoa New Zealand and is thus a valuable resource for managers, researchers and the public that will guide the management and conservation of seafloor communities. The atlas of seabed biodiversity for Aotearoa New Zealand is freely accessible via the open-Access database Zenodo under 10.5281/zenodo.7083642 (Stephenson et al., 2022)