bluuebunny/crossref_metadata_2025 huggingface dataset:
Seafloor evidence for palaeo‐ice streaming and calving of the grounded Irish Sea Ice Stream: Implications for the interpretation of its final deglaciation phase
Authors: VAN LANDEGHEM KATRIEN J. J. , WHEELER ANDY J. , MITCHELL NEIL C.
Published: January 2009

High resolution swath bathymetry data reveal a previously glaciated submarine terrain 20 km offshore Anglesey, north Wales, UK. The detailed documentation of remarkably well‐preserved subglacial and ice‐marginal bedforms provides evidence for a grounded part of the Irish Sea Ice Stream in a phase of deglaciation. The observed ribbed moraines, drumlins, flutes and eskers indicate a converging ice flow to the west, which then turns south into the deeper central Irish Sea Basin. Using the relative position of the bedforms, their spatial distribution and the morphological resemblance with bedforms described in the literature, this subglacial terrain is interpreted as representing a transition zone of frozen to thawed bed conditions during deglaciation, with an eastwards migrating thawing front that partly altered the edge of the surveyed ribbed moraine field by drumlinization. The abundant De Geer moraines and iceberg scour marks superimposed on drumlins and flutes reveal that the final retreat of the grounded ice margin in the surveyed area terminated into a water‐mass with extensive iceberg calving. As the glacial terrain is well preserved, no significant burial has taken place, either by glacially or terrestrially derived sediment. The strong tidal currents at present keep the submarine terrain swept clean of contemporary sediment cover.
Structure and composition of a tidewater glacier push moraine, Svalbard, revealed by DC resistivity profiling
Authors: KRISTENSEN LENE , JULIUSSEN HÅVARD , CHRISTIANSEN HANNE H. , HUMLUM OLE
Published: January 2009

A push moraine deposited by the surging tidewater glacier Paulabreen (Svalbard) was investigated using 2D resistivity profiling. Six longitudinal and transverse profiles were obtained on the moraine and the resistivities were compared with data from three boreholes. Four profiles indicate that the inner part of the moraine is ice‐cored and that the buried glacier ice is more than 30 m thick. A transverse profile shows evidence of basal crevasses near the former glacier margin. Three profiles cross the former glacier margin and onto a proglacial plain which dips slightly away from the former glacier margin. Low resistivities were encountered where borehole and field observations indicate that the plain consists of marine muds with a high salt content. This landform has previously been interpreted as a slab of seabed pushed up in front of the surging glacier, possibly facilitated by permafrost in the seabed. We suggest, alternatively, that the landform originated from sediments extruded from below (or pushed in front of) the glacier at the surge terminus and deposited as a debrisflow. Ground penetrating radar can reveal small‐scale structures, but larger structures and overall composition are better imaged by resistivity measurements.
Wound healing essentials: Let there be oxygen
Authors: Sen Chandan K.
Published: January 2009

The state of wound oxygenation is a key determinant of healing outcomes. From a diagnostic standpoint, measurements of wound oxygenation are commonly used to guide treatment planning such as amputation decision. In preventive applications, optimizing wound perfusion and providing supplemental O2 in the perioperative period reduces the incidence of postoperative infections. Correction of wound pO2 may, by itself, trigger some healing responses. Importantly, approaches to correct wound pO2 favorably influence outcomes of other therapies such as responsiveness to growth factors and acceptance of grafts. Chronic ischemic wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia is generally viewed as being angiogenic. This is true with the condition that hypoxia be acute and mild to modest in magnitude. Extreme near‐anoxic hypoxia, as commonly noted in problem wounds, is not compatible with tissue repair. Adequate wound tissue oxygenation is required but may not be sufficient to favorably influence healing outcomes. Success in wound care may be improved by a personalized health care approach. The key lies in our ability to specifically identify the key limitations of a given wound and in developing a multifaceted strategy to specifically address those limitations. In considering approaches to oxygenate the wound tissue it is important to recognize that both too little as well as too much may impede the healing process. Oxygen dosing based on the specific need of a wound therefore seems prudent. Therapeutic approaches targeting the oxygen sensing and redox signaling pathways are promising.
Microcirculation in mixed arterial/venous ulcers and the surrounding skin: Clinical study using a laser Doppler perfusion imager and capillary microscopy
Authors: Ambrozy Ewald , Waczulikova Iveta , Willfort‐Ehringer Andrea , Ehringer Herbert , Koppensteiner Renate , Gschwandtner Michael E.
Published: January 2009

To treat mixed skin ulcers effectively, it is important to investigate skin microcirculation in greater detail. Therefore, we used laser Doppler perfusion imaging and capillary microscopy for assessing both subpapillary and nutritive microcirculation in four defined regions of the skin in 17 patients with mixed ulcers caused by a combination of peripheral arterial occlusive disease and chronic venous insufficiency. Laser Doppler area flux was significantly higher in the ulcer areas than in the areas without granulation tissue and those in intact skin. The flux in the scars was higher than that in the intact skin or in the ulcer areas without granulation tissue. Capillary density in the intact skin was higher than the densities in nongranulation tissue areas, granulation areas, and scar areas (p<0.001 for all comparisons). To conclude, the ulcer areas without granulation tissue did not show a healing tendency due to poor subpapillary and nutritive perfusion; the granulation tissue exhibited high subpapillary perfusion as a sign of healing. In the scars, sufficient blood supply could be detected in both layers as a sign of an almost complete healing process. Blood supply in the intact skin is, however, already affected by distorted microcirculation in the ulcers.
Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized wound care center
Authors: Wicke Corinna , Bachinger Andreas , Coerper Stephan , Beckert Stefan , Witte Maria B. , Königsrainer Alfred
Published: January 2009

With the dramatic increase in the aging population, the study and care of wounds in the elderly have become priority topics for both researchers and clinicians. The effects of aging on wound healing in humans have remained controversial. The study was a 5‐year epidemiological evaluation of standardized data collected regularly during patients' visits at a specialized Wound Care Center with the aim to determine the key factors influencing the healing of chronic lower extremity wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure was statistically significantly lower in older patients compared with younger patients. The share of closed wounds decreased by nearly 25% in the elderly patients (≥70 years). The relationship between the patient's age and the proportion of wound closure was nonlinear. The effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60. The chronicity of the wounds was illustrated by their recurrent nature, their long duration, the presence of multiple wounds, and the frequency of concurrent infection. Comorbidity was documented by the coprevalence of up to three underlying diseases related to impaired wound healing. The present study clearly showed that aging affects chronic wound healing negatively.
Delayed reepithelialization and basement membrane regeneration after wounding in mice lacking CXCR3
Authors: Yates Cecelia C. , Whaley Diana , Hooda Shveta , Hebda Patricia A. , Bodnar Richard J. , Wells Alan
Published: January 2009

Wound healing is a complex, orchestrated series of biological events that is controlled by extracellular components that communicate between cell types to re‐establish lost tissue. We have found that signaling by ELR‐negative CXC chemokines through their common CXCR3 receptor is critical for dermal maturation during the resolving phase. In addition there needs to be complete maturation of the epidermis and regeneration of a delineating basement membrane for proper functioning. The role of this ligand–receptor system appears confounding as one ligand, CXCL4/(PF4), is present during the initial dissolution and two others, CXCL10/(IP‐10) and CXCL11/(IP‐9/I‐TAC), are expressed by keratinocytes in the later regenerative and resolving phases during which the basement membrane is re‐established. We examined CXCR3 signaling role in healing using a mouse lacking this receptor, as all three ligands act solely via the common receptor. Reepithelialization was delayed in CXCR3‐deficient mice in both full and partial‐thickness excisional wounds. Even at 90 days postwounding, the epidermis of these mice appeared less mature with lower levels of E‐cadherin and cytokeratin 18. The underlying basement membrane, a product of both dermal fibroblasts and epidermal keratinocytes, was not fully established with persistent diffuse expression of the matrix components laminin 5, collagen IV, and collagen VII throughout the wound bed. These results suggest that CXCR3 and its ligands play an important role in the re‐establishment of the basement membrane and epidermis. These studies further establish the emerging signaling network that involves the CXCR3 chemokine receptor and its ligands as a key regulator of wound repair.
Effect of estrogen and progesterone on macrophage activation during wound healing
Authors: Routley Claire E. , Ashcroft Gillian S.
Published: January 2009

Age‐related impaired wound healing leads to substantial morbidity and mortality along with a large financial burden to health services. There is accumulating evidence that the tissue damage associated with chronic wounds is initiated and propagated by an inappropriately excessive inflammatory response. Research on age‐related impaired wound healing suggests that the decline in sex steroid hormones with age may have a substantial influence on the inflammatory response in vivo. Topical and systemic estrogen treatments have shown an increased rate of healing by reducing inflammation, however the underlying mechanisms are little understood. In vitro studies also suggest progesterone may play a role in modulating inflammation. Macrophages are essential mediators of inflammation and wound healing. Macrophages can be activated in a classical or alternative manner in parallel with the TH1/TH2 dichotomy, respectively. Using a murine incisional wound healing model this study was carried out to investigate the roles of estrogen and progesterone on macrophage activation during the wound healing response. Our findings suggest with a reduction of steroid hormones following ovariectomy, alternatively activated macrophage markers (Fizz1 and Ym1) were reduced, with this effect being reversed with the administration of estrogen or progesterone; suggesting that with the reduction of steroid hormones macrophages are activated in a classical manner, promoting inflammation, whereas estrogen or progesterone are contributing toward macrophage activation in an alternative manner, driving wound repair, angiogenesis, and remodeling.
Characterizing omental adhesions by culturing cells isolated from a novel in vivo adhesion model
Authors: Gómez‐Gil Verónica , Pascual Gemma , García‐Honduvilla Natalio , Rodríguez Marta , Buján Julia , Bellón Juan M.
Published: January 2009

Although it has been established that postoperative adhesions in the peritoneal cavity are the consequence of injury to the peritoneum, there is much controversy over the nature of the cells giving rise to this neotissue. Here, we establish a novel adhesiogenic model in the rabbit to analyze the phenotype and proliferation in vitro of cells comprising adhesion tissue seven days postsurgery. Adhesion‐free omentum tissue was used as control. Cells derived from adhesions and from the control omentum were subcultured and characterized through immunofluorescence and Western blotting procedures to determine markers of cell differentiation and pluripotential, and viability and proliferation assays. Our findings indicate the existence of a mesenchymal population in the omentum revealed by markers of pluripotent cells with high angiogenic capacity. This population seems to be responsible for the adhesions formed in response to mesothelial damage. Depending on the local environment, mesenchymal cells are capable of in vivo differentiation towards at least two different cell phenotypes rendering two types of adhesions with clearly differentiated characteristics. One type of adhesion shows a highly vascularized adipose morphology containing cells differentiating into a vascular lineage. The other adhesions are fibrous with large amounts of collagen and comprised mainly of myofibroblasts conferring less compliance to this tissue.
Prostaglandin E1 prevents liver failure after excessive hepatectomy in the rat by up‐regulating Cyclin C, Cyclin D1, and Bclxl
Authors: Ishibe Atsushi , Togo Shinji , Kumamoto Takafumi , Watanabe Kazuteru , Takahashi Takuji , Shimizu Tetsuya , Makino Hirochika , Matsuo Kenichi , Kubota Toru , Nagashima Yoji , Shimada Hiroshi
Published: January 2009

Prostaglandin E1 (PGE1) has wide‐ranging effects on cytoprotection and may play a role in preventing liver failure following excessive hepatectomy. We examined the effect of PGE1 on hepatocyte apoptosis and liver regeneration after 95% hepatectomy in a rat model. PGE1 or vehicle was intravenously administered 30 minutes before and during hepatectomy. The extent of hepatocyte injury was evaluated by serum alanine aminotransferase and aspartate aminotransferase levels. To evaluate hepatocyte apoptosis and liver regeneration, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and Ki67 labeling were performed. The expression levels of Bcl‐xL, Bcl‐2, Bax, Cyclin C, Cyclin D1, Cyclin E, p21, transforming growth factor‐β, plasminogen activator inhibitor‐1, and glyceraldehyde‐2‐phosphate dehydrogenase mRNA were also examined by reverse transcription‐polymerase chain reaction. Survival was improved in the PGE1 group (26.6%), whereas all rats in the vehicle group died within 60 hours. PGE1 significantly suppressed the release of alanine aminotransferase and aspartate aminotransferase at 12 hours postoperatively. Pretreatment with PGE1 significantly increased the Ki67‐positive cell count and decreased the terminal deoxynucleotidyl transferase dUTP nick end labeling positive cell count after hepatectomy, and also significantly increased the expression levels of Bcl‐xL, Cyclin C, and Cyclin D1. Our results suggest that pretreatment with PGE1 may increase survival following hepatectomy by salvaging the remaining liver tissue, which it does by inhibiting apoptosis and stimulating hepatocyte proliferation.
Tyrosine phosphorylation of EGF‐R and PDGF‐R proteins during acute cutaneous wound healing process in mice
Authors: Gope Mohan L. , Gope Rajalakshmi
Published: January 2009

The effect of topical application of epidermal growth factor (EGF) and platelet‐derived growth factors (PDGFs) on the levels of EGF‐R and PDGF‐R proteins and their tyrosine phosphorylation were analyzed during an acute cutaneous wound healing process in mice. The growth factor‐treated wounds had optimum levels of receptor proteins as early as day 1 compared with the control, which had only a basal level. Analysis of the tyrosine phosphorylation of the receptor proteins in control and growth factor‐treated wounds indicated that they were phosphorylated until day 5 after wounding. Only the mature forms of α‐PDGF‐R and β‐PDGF‐R proteins were phosphorylated and not their precursors. Our results show that rapid attainment of maximum levels of growth factor receptor proteins and their tyrosine phosphorylation as early as day 1 and the maintenance of the same until day 3 appear to aid faster and better wound healing. Topical application of PDGF‐AA alone did not facilitate the wound healing process and it also antagonized the EGF‐medicated wound healing when applied premixed with EGF or within 30 minutes after EGF application. Under these conditions, the receptor proteins were not phosphorylated. Thus, an increased and sustained level of EGF‐R and PDGF‐R proteins and their tyrosine phosphorylation appear to accelerate the wound healing process.
Extracorporeal shock wave treatment modulates skin fibroblast recruitment and leukocyte infiltration for enhancing extended skin‐flap survival
Authors: Kuo Yur‐Ren , Wang Chun‐Ting , Wang Feng‐Sheng , Yang Kuender D. , Chiang Yuan‐Cheng , Wang Ching‐Jen
Published: January 2009

Extracorporeal shock wave (ESW) treatment has a positive effect of rescuing ischemic skin flaps. This study assessed whether ESW treatment rescues the compromised flap tissue by suppressing the apoptosis of ischemic tissue and recruiting tissue remodeling. We used a random‐pattern extended dorsal–skin‐flap (10 × 3 cm) rodent model. Thirty‐six male Sprague–Dawley rats were divided into three groups. Group I, the control group, received no treatment. Group II received one session of ESW treatment (500 impulses at 0.15 mJ/mm2) immediately after surgery. Group III received two sessions of ESW treatment, immediately and the day after the surgery. Results indicated that the necrotic area in the flaps in group II was significantly smaller than that of the flaps in group I (p<0.01). Transferase dUTP‐nick end labeling (TUNEL) analysis revealed a significant decrease in the number of apoptotic cells in group II. Hydrogen peroxide (H2O2) expression in circulation blood was significantly decreased in group II on the day after ESW treatment. Immunohistochemical staining indicated that compared with no treatment, ESW treatment could substantially increase proliferating cell nuclear antigen (PCNA), endothelial nitric oxide synthase, and prolyl 4‐hydroxylase (rPH) expression, reduce CD45 expression, and suppress 8‐hydroxyguanosine (8‐OG) expression in the ischemic zone of the flap tissue. In conclusion, ESW treatment administered at an optimal dosage exerts a positive effect of rescuing ischemic extended skin flaps. The mechanisms of action of ESWs involve modulation of oxygen radicals, attenuation of leukocyte infiltration, decrease in tissue apoptosis, and recruitment of skin fibroblasts, which results in increased flap tissue survival.
Prostaglandin E2 differentially regulates contraction and structural reorganization of anchored collagen gels by human adult and fetal dermal fibroblasts
Authors: Parekh Aron , Sandulache Vlad C. , Singh Tripti , Cetin Selma , Sacks Michael S. , Dohar Joseph E. , Hebda Patricia A.
Published: January 2009

Contraction and remodeling of granulation tissue by fibroblasts is a crucial component of dermal wound healing. Postnatal wounds heal with imperfect repair and scar formation, whereas tissue repair in fetal wounds is regenerative. Prostaglandin E2 (PGE2) modulates the behavior of fibroblasts in the wound bed. This study was designed to investigate the mechanism by which PGE2 regulates an in vitro model of granulation tissue, anchored collagen gels, by human adult and fetal dermal fibroblasts. We hypothesized that PGE2 differentially regulates contraction and remodeling of anchored collagen gels by these fibroblast phenotypes. These results indicate that once tension was generated, fetal fibroblasts exerted lower contractile forces resulting in less collagen contraction. This coincided with less prominent stress fibers, yet fetal fibroblasts were able to substantially remodel the collagen architecture. This mechanism was differentially modulated by PGE2 and was mimicked with a PGE2 receptor agonist, indicating a cyclic adenosine monophosphate (cAMP)‐dependent mechanism through the EP2 receptor. However, direct up‐regulation of cAMP led to decreases in contraction and remodeling by both fibroblast phenotypes indicating an altered signaling pathway. Therefore, targeting cAMP via the EP2 receptor could potentially decrease adult fibroblast contractile forces to the levels of the fetal fibroblast phenotype in order to decrease dermal scarring.
Emblica officinalis exerts wound healing action through up‐regulation of collagen and extracellular signal‐regulated kinases (ERK1/2)
Authors: Sumitra Miriyala , Manikandan Panchatcharam , Gayathri Vinaya Subramani , Mahendran Panchatcharam , Suguna Lonchin
Published: January 2009

During wound healing, the wound site is rich in oxidants, such as hydrogen peroxide, mostly contributed by neutrophils and macrophages. Ascorbic acid and tannins of low molecular weight, namely emblicanin A (2,3‐di‐O‐galloyl‐4,6‐(S)‐hexahydroxydiphenoyl‐2‐keto‐glucono‐δ‐lactone) and emblicanin B (2,3,4,6‐bis‐(S)‐hexahydroxydiphenoyl‐2‐keto‐glucono‐δ‐lactone) present in Emblica officinalis (emblica), have been shown to exhibit a very strong antioxidant action. We proposed that addition of these antioxidants to the wound microenvironment would support the repair process. The present investigation was undertaken to determine the efficacy of emblica on dermal wound healing in vivo. Full‐thickness excision wounds were made on the back of the rat and topical application of emblica accelerated wound contraction and closure. Emblica increased cellular proliferation and cross‐linking of collagen at the wound site, as evidenced by an increase in the activity of extracellular signal‐regulated kinase 1/2, along with an increase in DNA, type III collagen, acid‐soluble collagen, aldehyde content, shrinkage temperature and tensile strength. Higher levels of tissue ascorbic acid, α‐tocopherol, reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase support the fact that emblica application promotes antioxidant activity at the wound site. In summary, this study provides firm evidence to support that topical application of emblica represents a feasible and productive approach to support dermal wound healing.
Impaired cutaneous wound healing in mice lacking tetranectin
Authors: Iba Kousuke , Hatakeyama Naoko , Kojima Takashi , Murata Masaki , Matsumura Tadaki , Wewer Ulla M. , Wada Takuro , Sawada Norimasa , Yamashita Toshihiko
Published: January 2009

Tetranectin was originally purified from human serum on the basis of plasminogen kringle 4‐binding properties. Tetranectin enhances plasminogen activation by a tissue‐type plasminogen activator so that it has been suggested to play a role in tissue remodeling. We have generated mice with a targeted disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin‐null mice compared with wild‐type mice. A single full‐thickness incision was made in the dorsal skin. By 14 days after the incision, the wounds fully healed in all wild‐type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild‐type mice showed complete reepithelialization and healed by 14 days after the incision. However, those of tetranectin‐null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process.
Depth of penetration of negative pressure wound therapy into underlying tissues
Authors: Murphey Gary C. , Macias Brandon R. , Hargens Alan R.
Published: January 2009

Negative pressure wound therapy has become ubiquitous in orthopedic surgery and it is therefore important to understand the physiologic conditions of this therapy. The purpose of this study was to determine the magnitude and depth of negative pressure transmission into underlying muscle tissue in a wound model. We hypothesized that the negative pressure is not transmitted beyond 2 mm into underlying muscle tissue. Using both an isolated muscle and a live animal wound model, we applied open cell foam dressing to the tissue. Using a series of vacuum‐assisted closure negative pressure settings (0, −75, −125, −200 mmHg) interstitial fluid pressure was measured in the underlying tissue with a solid‐state pressure transducer catheter at 1/10 mm depth intervals. In the ex vivo isolated‐muscle model, the effect of negative pressure wound therapy on interstitial fluid pressure was extinguished and not significantly different than controls at a depth <2 mm. In the live animal wound model, the magnitude of interstitial fluid pressures corresponded directly with negative pressure settings (p<0.01) and inversely with depth into muscle (p<0.01). Interstitial fluid pressures were significantly (p<0.05) less than control interstitial fluid pressures (0 mmHg setting) at depths of 0.5, 0.4, and 0.9 mm below the foam/muscle interface when the applied pressures were −75, −125, and −200 mmHg, respectively. Negative pressure wound therapy penetrates no more than 1 mm into rabbit wound tissue at the highest negative pressure setting (−200 mmHg) when using open‐cell foam dressing.
FGF‐10 and specific structural elements of dermatan sulfate size and sulfation promote maximal keratinocyte migration and cellular proliferation
Authors: Radek Katherine A. , Taylor Kristen R. , Gallo Richard L.
Published: January 2009

Fibroblast growth factor‐10 (FGF‐10) is essential for epithelial development, while other members of this family, such as FGF‐7, are not. FGF‐10 is abundantly released into wounds following injury, and likely an essential growth factor required for this process. To evaluate how activation of this growth factor is controlled, multiple glycosaminoglycans were combined with FGF‐10 assayed by measurement of the proliferation of cell lines expressing FGF receptor‐2‐IIIb, or keratinocyte migration in an in vitro wound repair assay. Dermatan sulfate (DS) exhibited greater potency than heparan sulfate or other chondroitin sulfates found in wounds. Structural variants of DS between 10 and 20 disaccharides containing iduronic acid showed maximal capacity to enable FGF‐10 receptor stimulation. Furthermore, FGF‐10 and DS markedly enhanced migration of keratinocytes in an in vitro wound scratch assay, while FGF‐7 or other glycosaminoglycans did not. These data strongly suggest that FGF‐10 activity is uniquely important in wound repair and that specific DS structural properties are necessary to promote FGF‐10 function. These observations identify a novel interplay between DS and FGF‐10 in mediating wound repair.
A novel cell‐adhesive scaffold material for delivering keratinocytes reduces granulation tissue in dermal wounds
Authors: Masuda Ryuji , Mochizuki Mayumi , Hozumi Kentaro , Takeda Akira , Uchinuma Eiju , Yamashina Shohei , Nomizu Motoyoshi , Kadoya Yuichi
Published: January 2009

Novel peptide‐conjugated chitosan membranes were fabricated and used to deliver keratinocytes to dermal wounds in mice. Three active peptides of 12 or 13 amino acids each, RLVSYNGIIFFLK (A5G27), ASKAIQVFLLAG (A5G33), and AGTFALRGDNPQG (A99) were selected from a cell‐adhesive peptide library of laminin, a major constituent of basement membrane. The peptides were synthesized and coupled to chitosan membranes, and the resulting peptide–chitosan membranes were tested for keratinocyte attachment. Two of the peptides that bind to cell surface heparin‐like receptors (A5G27 and A5G33) were found to promote strong keratinocyte attachment, whereas the one that binds to integrin (A99) was inactive. Subsequently, A5G27– and A5G33–chitosan membranes were tested as vehicles for keratinocyte delivery in a wound model. We found that keratinocytes were delivered into the full‐thickness wound with either membrane. Using the A5G33–chitosan membrane, we further evaluated the activity of the delivered keratinocytes in wound healing. Immunohistochemistry for granulation tissue markers, including tenascin and α‐smooth muscle actin, showed that keratinocyte delivery by the present peptide–chitosan membranes in the wound bed provided a favorable condition for keratinocyte migration along the wound surface and reduced granulation tissue formation.
Tissue engineering a model for the human ear: Assessment of size, shape, morphology, and gene expression following seeding of different chondrocytes
Authors: Kusuhara Hirohisa , Isogai Noritaka , Enjo Mitushiro , Otani Hitoshi , Ikada Yoshito , Jacquet Robin , Lowder Elizabeth , Landis William J.
Published: January 2009

This study examines the tissue engineering of a human ear model through use of bovine chondrocytes isolated from four different cartilaginous sites (nasoseptal, articular, costal, and auricular) and seeded onto biodegradable poly(l‐lactic acid) and poly(l‐lactide‐ɛ‐caprolactone) (50 : 50) polymer ear‐shaped scaffolds. After implantation in athymic mice for up to 40 weeks, cell/scaffold constructs were harvested and analyzed in terms of size, shape, histology, and gene expression. Gross morphology revealed that all the tissue‐engineered cartilages retained the initial human auricular shape through 40 weeks of implantation. Scaffolds alone lost significant size and shape over the same period. Quantitative reverse transcription‐polymerase chain reaction demonstrated that the engineered chondrocyte/scaffolds yielded unique expression patterns for type II collagen, aggrecan, and bone sialoprotein mRNA. Histological analysis showed type II collagen and proteoglycan to be the predominant extracellular matrix components of the various constructs sampled at different implantation times. Elastin was also present but it was found only in constructs seeded with auricular chondrocytes. By 40 weeks of implantation, tissue‐engineered cartilage of costal origin became calcified, marked by a notably high relative gene expression level of bone sialoprotein and the presence of rigid, nodular protrusions formed by mineralizing rudimentary cartilaginous growth plates. The collective data suggest that nasoseptal, articular, and auricular cartilages represent harvest sites suitable for development of tissue‐engineered human ear models with retention over time of three‐dimensional construct architecture, gene expression, and extracellular matrix composition comparable to normal, nonmineralizing cartilages. Calcification of constructs of costal chondrocyte origin clearly shows that chondrocytes from different tissue sources are not identical and retain distinct characteristics and that these specific cells are inappropriate for use in engineering a flexible ear model.
Expression of patched, prdm1 and engrailed in the lamprey somite reveals conserved responses to Hedgehog signaling
Authors: Hammond Katherine L. , Baxendale Sarah , McCauley David W. , Ingham Philip W. , Whitfield Tanya T.
Published: January 2009

SUMMARY
In the zebrafish embryo, expression of the prdm1 and patched1 genes in adaxial cells is indicative of their specification to give rise to slow twitch muscle fibers in response to Hedgehog (Hh) signaling. Subsets of these slow twitch muscle progenitors activate engrailed (eng) strongly in response to high‐level Hh signaling, and differentiate into muscle pioneer cells, which are important for subsequent development of the horizontal myoseptum. In addition, eng is expressed more weakly in medial fast fibers in response to lower Hh levels. Somite morphology in the lamprey, an agnathan (jawless) vertebrate, differs significantly from that of teleosts. In particular, the lamprey does not have clear epaxial/hypaxial domains, lacks a horizontal myoseptum, and does not appear to possess distinct populations of fast and slow fibers in the embryonic somite. Nevertheless, Hh is expressed in the midline of the lamprey embryo, and we report here that, as in zebrafish, homologues of patched and prdm1 are expressed in adaxial regions of the lamprey somite, and an eng homologue is also expressed in the somite. However, the lamprey adaxial region does not exhibit the same distinct adaxial cell morphology as in the zebrafish. In addition, the expression of follistatin is not excluded from the adaxial region, and eng is not detected in discrete muscle pioneer‐like cells. These data suggest the presence of conserved responses to Hh signaling in lamprey somites, although the full range of effects elicited by Hh in the zebrafish somite is not recapitulated.
Musculature in sipunculan worms: ontogeny and ancestral states
Authors: Schulze Anja , Rice Mary E.
Published: January 2009

SUMMARY
Molecular phylogenetics suggests that the Sipuncula fall into the Annelida, although they are morphologically very distinct and lack segmentation. To understand the evolutionary transformations from the annelid to the sipunculan body plan, it is important to reconstruct the ancestral states within the respective clades at all life history stages. Here we reconstruct the ancestral states for the head/introvert retractor muscles and the body wall musculature in the Sipuncula using Bayesian statistics. In addition, we describe the ontogenetic transformations of the two muscle systems in four sipunculan species with different developmental modes, using F‐actin staining with fluorescent‐labeled phalloidin in conjunction with confocal laser scanning microscopy. All four species, which have smooth body wall musculature and less than the full set of four introvert retractor muscles as adults, go through developmental stages with four retractor muscles that are eventually reduced to a lower number in the adult. The circular and sometimes the longitudinal body wall musculature are split into bands that later transform into a smooth sheath. Our ancestral state reconstructions suggest with nearly 100% probability that the ancestral sipunculan had four introvert retractor muscles, longitudinal body wall musculature in bands and circular body wall musculature arranged as a smooth sheath. Species with crawling larvae have more strongly developed body wall musculature than those with swimming larvae. To interpret our findings in the context of annelid evolution, a more solid phylogenetic framework is needed for the entire group and more data on ontogenetic transformations of annelid musculature are desirable.
Lumbar Stimulation Belt for Therapy of Low‐Back Pain
Authors: Popović Dejan B. , Bijelić Goran , Miler Vera , Došen Strahinja , Popović Mirjana B. , Schwirtlich Laszlo
Published: January 2009

We developed the STIMBELT, an electrical stimulation system that comprises a lumbar belt with up to eight pairs of embedded electrodes and an eight‐channel electronic stimulator. The STIMBELT is an assistive system for the treatment of low‐back pain (LBP). We describe here technical details of the system and summarize the results of its application in individuals with subacute and chronic LBP. The direct goals of the treatment were to relieve pain, reduce muscle spasms, increase strength and range of motion, and educate individuals with LBP in reducing the chances of its reoccurrence. The outcome measures include: a Visual Analogue Scale (VAS), the Oswestry LBP Disability Questionnaire, the Short Form (SF)‐12 health survey, and the Manual Muscle Test. The results indicate significant benefits for individuals who use the STIMBELT in addition to the conventional therapy as opposed to only the conventional therapy.
The Relationship Between Leptin Level and Oxidative Status Parameters in Hemodialysis Patients
Authors: Horoz Mehmet , Aslan Mehmet , Koylu Ahmet O. , Bolukbas Cengiz , Bolukbas Filiz F. , Selek Sahbettin , Erel Ozcan
Published: January 2009

Both serum leptin level and oxidative stress are increased in hemodialysis (HD) patients. In the present study, we aimed to investigate whether there is association between oxidative status and leptin level in HD patients. Thirty‐five HD patients and 25 healthy controls were enrolled in the present study. Serum leptin level, total peroxide (TP) level, total antioxidant capacity (TAC), and oxidative stress index (OSI) were determined. Serum leptin level, TP level, and OSI were significantly higher in HD patients than controls (all P < 0.001) while TAC was lower (P < 0.001). In HD patients, serum leptin level was significantly correlated with TP level and OSI (r = 0.372, P <  0.001 and r = 0.409, P < 0.001, respectively). The correlation of serum leptin level with TP level and OSI remained statistically significant after adjusting for age, gender, and body‐fat percentage (r = 0.446, P < 0.001 and r = 0.463, P < 0.001, respectively). Hyperleptinemia seems to be associated with increased oxidative stress in HD patients, and this association may provide better understanding about the disorders related to either elevated serum leptin levels and/or increased oxidative stress in HD patients.
Contribution of NADH Increases to Ethanol’s Inhibition of Retinol Oxidation by Human ADH Isoforms
Authors: Chase Jennifer R. , Poolman Mark G. , Fell David A.
Published: January 2009

Background:  A decrease in retinoic acid levels due to alcohol consumption has been proposed as a contributor to such conditions as fetal alcohol spectrum diseases and ethanol‐induced cancers. One molecular mechanism, competitive inhibition by ethanol of the catalytic activity of human alcohol dehydrogenase (EC 1.1.1.1) (ADH) on all‐trans‐retinol oxidation has been shown for the ADH7 isoform. Ethanol metabolism also causes an increase in the free reduced nicotinamide adenine dinucleotide (NADH) in cells, which might reasonably be expected to decrease the retinol oxidation rate by product inhibition of ADH isoforms.

Methods:  To understand the relative importance of these two mechanisms by which ethanol decreases the retinol oxidation in vivo we need to assess them quantitatively. We have built a model system of 4 reactions: (1) ADH oxidation of ethanol and NAD+, (2) ADH oxidation of retinol and NAD+, (3) oxidation of ethanol by a generalized Ethanoloxidase that uses NAD+, (4) NADHoxidase which carries out NADH turnover.

Results:  Using the metabolic modeling package ScrumPy, we have shown that the ethanol‐induced increase in NADH contributes from 0% to 90% of the inhibition by ethanol, depending on (ethanol) and ADH isoform. Furthermore, while the majority of flux control of retinaldehyde production is exerted by ADH, Ethanoloxidase and the NADHoxidase contribute as well.

Conclusions:  Our results show that the ethanol‐induced increase in NADH makes a contribution of comparable importance to the ethanol competitive inhibition throughout the range of conditions likely to occur in vivo, and must be considered in the assessment of the in vivo mechanism of ethanol interference with fetal development and other diseases.
Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins
Authors: Lange Andreas , Kistler Claudia , Jutzi Tanja B. , Bazhin Alexandr V. , Klemke Claus Detlev , Schadendorf Dirk , Eichmüller Stefan B.
Published: January 2009

Abstract:  The identification of tumor‐specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post‐translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane‐associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane‐bound proteins. Fractionated mRNAs from the cutaneous T‐cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT‐PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane‐associated proteins.
The Conners' 10‐item scale: findings in a total population of Swedish 10–11‐year‐old children
Authors: Westerlund Joakim , Ek Ulla , Holmberg Kirsten , Näswall Katharina , Fernell Elisabeth
Published: January 2009

Aim: To present normative data for the Swedish version of the Conners' 10‐item scale, to validate the scale by comparing children with and without attention deficit/hyperactivity disorder (ADHD), to explore the factor structure of this scale and to investigate behavioural characteristics and gender differences among 10‐ to 11‐year‐old children, as rated by parents and teachers respectively.

Methods: Parents and teachers rated 509 10‐ to 11‐year‐old children (261 boys and 248 girls) from a population‐based cohort in a Swedish municipality.

Results: The Conners' 10‐item scale discriminated very well between children with and without ADHD. Confirmatory factor analyses confirmed a two‐dimensional structure of the scale with items measuring restless/impulsive behaviour in one factor and items measuring emotional lability in another. An ANOVA revealed that parents and teachers reported different behavioural characteristics in boys as compared to girls.

Conclusion: The Conners' 10‐item scale is a valid screening instrument for identification of ADHD. The two subscales can be used separately, in addition to the total score, to get a more detailed picture of the child's behaviour. Parents and teachers pay attention to different aspects of problem behaviour in boys and girls. The less disruptive behaviour of girls needs to be highlighted.
Development and Testing of the Context Assessment Index (CAI)
Authors: McCormack Brendan , McCarthy Geraldine , Wright Jayne , Coffey Alice
Published: January 2009

Aim: To test the psychometric properties of the Context Assessment Index (CAI).

 Background: We used the Promoting Action on Research Implementation in Health Services Framework (PARIHS) as the theoretical framework for the study. The framework shows the successful implementation of evidence in practice as dependent on the inter‐relationship of the nature of the evidence, the quality of the context, and expert facilitation. However, a comprehensive method of assessing context has not yet been available.

Methods: A five‐stage instrument development and testing methodology was used. Principal components analysis, exploratory factor analysis, and expert panel feedback were used to develop and refine the CAI model. The model was further tested for psychometric properties of internal consistency and test–retest scores. Telephone interviews were conducted with expert nurses to gauge the usability of the instrument. These stages of development and testing resulted in a final 37‐item, five‐factor CAI model.

Findings: This 37‐item model was accepted as a reasonable explanation of the data. The measures of homogeneity were calculated for each of the five factors to measure internal reliability. The Cronbach's alpha score for the complete questionnaire was estimated at 0.93. All five factors achieved a satisfactory estimated level of internal consistency in scoring, ranging from 0.78 to 0.91. Test–retest scores indicate reliability of the findings, and the feedback from focus group participants suggests that the instrument has practical utility.

Conclusions: The CAI provides clinicians with the means to assess and understand the context in which they work and the effect this has on using evidence in practice.
Identification and Expression of Floral Organ Homeotic Genes from Alpinia oblongifolia (Zingiberaceae)
Authors: Xia Yong‐Mei , Gao Xue‐Mei , Li Qing‐Jun
Published: January 2009

Current understanding of the classical ABC model of floral development has provided a new set of characters to evaluate floral evolution. However, what is still lacking is a clear assessment of this genetic program across monocots. Here, to investigate the evolution of members of class A and B genes in monocots, we report the sequence characteristic and transcript expression of three new MADS‐box genes in Alpinia oblongifolia Hayata. Sequence and phylogenetic analysis reveals that these genes are FUL‐like and AP3‐like. Therefore, they were termed AoFL1, AoFL2 and AoAP3. AoFL1 contains the FUL motif, but AoFL2 lacks this motif. Their expression revealed by in situ hybridization may reflect the ancestral function of FUL‐like genes in the specification of inflorescence and floral meristems. The AoAP3 gene contains two conserved motifs, the PI‐derived and paleoAP3 motifs. The AoAP3 transcripts located to the corolla and stamen, and hybridization signals were detected in the central whorl. These expression patterns suggest that the functions of homologous organ identity genes are diversified in A. oblongifolia. The implications of these findings on the conservation of homologous gene function are discussed.
Reading, Writing and Radicalism: Right-Wing Women and Education in the Post-War Years
Authors: Benowitz June Melby
Published: January 2009

The headlines “Who's Trying to Ruin Our Schools?” and “Danger's Ahead in the Public Schools” grabbed the attention of the American public during the early 1950s as mainstream publications reacted to efforts by right-wing organizations to influence the curricula of America's elementary and secondary schools. “A bewildering disease that threatens to reach epidemic proportions has infected the public schools of America,” warned John Bainbridge in a two-part series forMcCall'sin September and October 1952. “The disease does not attack the body but, rather, the mind and the spirit. It produces unreasoning fear and hysteria.” Bainbridge was writing of efforts of some men, women, and their organizations to censor textbooks; to standardize the curriculum; to eliminate teaching about communism, the United Nations and the workings of governments outside of the United States; and to discredit teaching methods used in both public K-12 schools and in the nation's colleges. These activists also sought to ban those who did not subscribe to a specific way of thinking from speaking before students and at educational conferences and gatherings. As a consequence, in the late 1940s and early 1950s a number of American communities were in an uproar over what the country's youth were being taught, and who was doing the teaching.
Negotiating Pregnancy at Work: Public and Private Conflicts
Authors: Greenberg Danna , Ladge Jamie , Clair Judy
Published: January 2009

While pregnancy in the workplace is a fairly common occurrence today, there are still numerous covert and overt biases women must navigate when pregnant at work. Current research on pregnancy in the workplace has primarily highlighted the substantive negotiations that pregnant women engage in with regards to maternity leave and role definition. In this study, we move beyond existing research to explore the full range of issues pregnant women negotiate in the workplace. Through in‐depth interviews with 30 professional women who were pregnant for the first time, we identify both intrapersonal and interpersonal issues women negotiate during pregnancy and we explore why these issues arise and how women respond to them. We conclude with a discussion of the implications of this study for both theory and practice.