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This study investigated whether there are differences in the ability of wound dressings to modulate certain factors known to affect wound healing. A selection of antimicrobial dressings ( AQUACEL® Ag Extra™, AQUACEL® Ag+ Extra™, IODOFLEX™, ACTICOAT™ 7 and PROMOGRAN PRISMA™ matrix) were tested for their effect on both bacterial bioburden and human dermal fibroblasts. Some dressings underwent further evaluation for activity against Pseudomonas aeruginosa biofilms using a colony-drip flow reactor model. The ability of in vitro biofilms to produce proteases, and the effect of PROMOGRAN PRISMA matrix on such proteases, was also investigated. All antimicrobial dressings tested reduced vegetative bacterial load; however, only PROMOGRAN PRISMA matrix was able to significantly reduce biofilm populations ( P = 0·01). Additionally, PROMOGRAN PRISMA matrix was the only dressing that did not inhibit dermal fibroblast growth. All other dressings were detrimental to cell viability. In vitro biofilms of Pseudomonas aeruginosa were demonstrated as being capable of releasing bacterial proteases into their surroundings, and incubation with PROMOGRAN PRISMA matrix led to a 77% reduction in activity of such proteases ( P = 0·002). The unique ability of PROMOGRAN PRISMA matrix to reduce in vitro vegetative bacteria, biofilm bacteria and bacterial proteases while still allowing dermal fibroblast proliferation may help rebalance the wound environment and reduce the occurrence of infection. [ABSTRACT FROM AUTHOR]

ABSTRACT It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples ( n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies. [ABSTRACT FROM AUTHOR]

For many spatial processes, there is a natural need to find out the point of origin on the basis of the available scatter of observations; think, for instance, of finding out the home base of a criminal given the actual distribution of crime scenes, or the outbreak source of an epidemics. In this article, we build on the topological weighted centroid (TWC) methodology that has been applied in previous research to the reconstruction of space syntax problems, for example, of problems where all relevant entities are of spatial nature so that the relationships between them are inherently spatial and need to be properly reconstructed. In this article, we take this methodology to a new standard by tackling the new and challenging task of analyzing space semantics problems, where entities are characterized by properties of a nonspatial nature and must therefore be properly spatialized. We apply the space semantics version of the TWC methodology to a particularly hard problem: the reconstruction of global political and economic relationships on the basis of a small-dimensional qualitative dataset. The combination of a small set of spatial and nonspatial sources of information allows us to elucidate some intriguing and counterintuitive properties of the inherent global economic order and, in particular, to highlight its long-term structural features, which interestingly point toward the idea of longue durée developed by the distinguished French historian Fernand Braudel. [ABSTRACT FROM AUTHOR]

The deer remains from the renowned Palaeolithic site of Isernia la Pineta (southern Italy) are revised. Both material already published, and new specimens from the last 15 years of excavation, is taken into account and some identifications are revised. The published assemblage consists of Megaceroides solilhacus, Cervus sp. cf. C. elaphus acoronatus, Dama sp. cf. D. clactoniana and Capreolus sp. The literature dealing with these species is discussed and the problems still unresolved are outlined. The giant deer, now assigned by most authors to the genus Praemegaceros as P. solilhacus, is the largest and most common deer species at the site, represented by numerous antler fragments plus a few isolated teeth and fragmentary postcranial elements. The retrieval of new, well-preserved specimens, namely one nearly complete antler, plus a distal portion of palmation, two neural skulls and one premaxillary bone, allows a better characterization of this otherwise still poorly understood species. The sub-specific attribution of the red deer, in the lack of more complete antler specimens, is still dubious. The fallow deer remains probably belong to Dama roberti, a recently described species from the early Middle Pleistocene of Western Europe. The morphology of the lower portion of the only preserved antler fits better with this species rather than with D. clactoniana, to which it was previously tentatively assigned. At last, the specific identity of the few roe deer remains from Isernia is discussed, but the problem remains unanswered because of lack of agreement, in the literature, about the taxonomy of the Pleistocene species. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Within chronic wounds, the relationship between the clinical diagnosis of infection and bacterial/immuno-inflammatory responses is imprecise. This study prospectively examined the interrelationship between clinical, microbiological, and proinflammatory biomarker levels between chronic venous leg ulcers ( CVLUs) and diabetic foot ulcers ( DFUs). Wound swabs and fluids were collected from CVLUs ( n = 18) and DFUs ( n = 15) and diagnosed clinically as noninfected or infected; and qualitative/quantitative microbiology was performed. CVLU and DFU fluids were also analyzed for cytokine, growth factor, receptor, proteinase/proteinase inhibitor; and oxidative stress biomarker (protein carbonyl, malondialdehyde, and antioxidant capacity) levels. While no correlations existed between clinical diagnosis, microbiology, or biomarker profiles, increasing bacterial bioburden (≥107 colony-forming unit/mL) was associated with significant alterations in cytokine, growth factor, and receptor levels. These responses contrasted between ulcer type, with elevated and decreased cytokine, growth factor, and receptor levels in CVLUs and DFUs with increasing bioburden, respectively. Despite proteinase biomarkers exhibiting few differences between CVLUs and DFUs, significant elevations in antioxidant capacities correlated with increased bioburden in CVLU fluids, but not in DFUs. Furthermore, oxidative stress biomarker levels were significantly elevated in all DFU fluids compared with CVLUs. This study provides further insight into the contrasting disease-specific host responses to bacterial challenge within infected CVLUs and DFUs. [ABSTRACT FROM AUTHOR]

The continental highlands of the Cameroon Volcanic Line ( CVL) represent biological 'sky islands' with high levels of species richness and endemism, providing the ideal opportunity to understand how orogenesis and historical climate change influenced species diversity and distribution in these isolated African highlands. Relationships of puddle frogs ( Phrynobatrachus) endemic to the CVL are reconstructed to examine the patterns and timing of puddle frog diversification. Historical distributions were reconstructed using both elevation and geography data. Puddle frogs diversified in the CVL via several dispersal and vicariance events, with most of the locally endemic species distributed across the northern part of the montane forest area in the Bamenda- Banso Highlands ( Bamboutos Mts., Mt. Lefo, Mt. Mbam, Mt. Oku and medium elevation areas connecting these mountains). Two new species, P. jimzimkusi sp. n. and P. njiomock sp. n., are also described based on molecular analyses and morphological examination. We find that these new species are most closely related to one another and P. steindachneri with the ranges of all three species overlapping at Mt. Oku. Phrynobatrachus jimzimkusi sp. n. is distributed in the southern portion of the continental CVL, P. njiomock sp. n. is endemic to Mt. Oku, and P. steindachneri is present in the northeastern part of the montane forest area. Both new species can be distinguished from all other puddle frogs by a combination of morphological characters, including their large size, ventral coloration and secondary sexual characteristics present in males. These results highlight the Bamenda- Banso Highlands, and specifically emphasize Mt. Oku, as a centre of diversification for puddle frogs, supporting the conservation importance of this region. Our results also provide new insights into the evolutionary processes shaping the CVL 'sky islands', demonstrating that lineage diversification in these montane amphibians is significantly older than expected with most species diverging from their closest relative in the Miocene. Whereas climatic changes during the Pliocene and Pleistocene shaped intraspecific diversification, most speciation events were significantly older and cannot be linked to Africa's aridification in response to Pleistocene climate fluctuations. [ABSTRACT FROM AUTHOR]

A sensitive and selective method, using liquid chromatography-ionspray mass spectrometry, was developed and validated for the simultaneous determination of Estracyt (estramustine phosphate) and its four metabolites, estramustine, estromustine, estrone and estradiol, in human plasma. Deuterated internal standards were available for all analytes. The five compounds were extracted from plasma by protein precipitation with acetonitrile. The chromatographic separation was performed using a Zorbax SB C18, (150 × 4.6 mm i.d., 5 µm) reversed-phase column under gradient conditions with a mobile phase containing 2 m m ammonium acetate buffer (pH 6.8) and acetonitrile. MS detection was by electrospray ionization with multiple reaction monitoring in the positive ion mode for estramustine phosphate, estromustine and estramustine, and in the negative ion mode for estrone and estradiol. The limit of quantitation was 10 ng/mL for estramustine phosphate, 3 ng/mL for estromustine, estramustine and estrone and 30 ng/mL for estradiol. Linearity was verified from these LLOQs up to about 4000 ng/mL for the parent drug and 2000 ng/mL for the metabolites. Inter-day precision and accuracy values were all less than 15%. This assay was applied successfully to the routine analysis of human plasma samples collected in cancer patients administered estramustine phosphate intravenously. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chemokines regulate the chemotaxis, development, and differentiation of many cell types enabling the regulation of routine immunosurveillance and immunological adaptation. CC chemokine receptor 1 (CCR1) is the target of 11 chemokines. This promiscuity of receptor-ligand interactions and the potential for functional redundancy has led us to investigate the selective activation of CCR1-coupled pathways by known CCR1 agonists. Chemokines leukotactin-1, macrophage inflammatory protein (MIP)-1α, monocyte chemotactic peptide (MCP)-3, RANTES, and MIP-1δ all inhibited adenylyl cyclase activity in cells transiently transfected with CCR1. In contrast, only MIP-1δ was unable to signal via G-, G- or chimeric 16z44-coupled pathways. In a stable cell line expressing CCR1 and Gα, all of these five chemokines along with hemofiltrate CC chemokine (HCC)-1 and myeloid progenitor inhibitory factor (MPIF)-1 were able to stimulate G-coupled pathways, but MIP-1δ, HCC-1 and MPIF-1 were unable to activate G-mediated stimulation of phospholipase Cβ activity. In addition, MIP-1δ was unable to promote the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. This suggests that different chemokines are able to selectively activate CCR1-coupled pathways, probably because of differentintrinsic ligand efficacies. CCR1 and Gα or Gα are co-expressed in several cell types and we hypothesize that selective activation of chemokine receptors provides a mechanism by which chemokines are able to fine-tune intracellular signaling pathways. [ABSTRACT FROM AUTHOR]