Integration of blood outgrowth endothelial cells in dermal fibroblast sheets promotes full thickness wound healing

status: publishe

Visualization techniques of the facial arteries

Background As the face is known for its extreme variation in vascular anatomy and the number of filler-associated complications due to intra-arterial injection is increasing, we are in need of a method to visualize anyone's individual arterial anatomy of the face in a completely harmless way. Aims The different medical imaging methods and a recently developed MRA protocol are reviewed. Methods The literature of the last twenty years-with special attention for the last five years-concerning the different medical imaging modalities of the facial arteries was reviewed. Results A harmless visualisation of the facial arteries is currently only possible with US or MRA. US may identify single vessels but never the complete arterial network. A combination of IR "heat enhancement" and a MRA 3D-TOF sequence might make it feasible to visualize a large number of facial arteries in a risk-free, radiation-free, contrast-free and non-invasive way. Conclusion Currently, a new combination of IR "heat enhancement" and a MRA 3D-TOF sequence might be the only method to visualize a large number of facial arteries

Nonviral Transfection Strategies for Keratinocytes, Fibroblasts, and Endothelial Progenitor Cells for Ex Vivo Gene Transfer to Skin Wounds

In a search for the optimal nonviral gene transfer technique in epidermal and dermal supportive extracellular matrix studies, we investigated the efficiency of late generation liposomal transfection reagents and nucleofection of fibroblasts (FBs), endothelial progenitor cells (EPCs), and keratinocytes (KCs) as essential indicators of healing skin wounds. FBs, KCs, and EPCs were grown under serum-reduced conditions and manipulated according to optimized in vitro manufacturer protocols. Fugene HD, Effectene, PEI, and Lipofectin were compared to Amaxa Nucleofection. A green fluorescent protein (GFP)-encoded reporter gene plasmid was transfected, and transfection efficiencies were determined by green-fluorescence-activated cell sorting. Normal cell morphologies were observed after either transfection or nucleofection. For KC cell cultures, Fugene HD resulted in the highest transfection efficiency in human (41%) and porcine (42%) KCs. For EPCs, Effectene was optimal for human-derived cells (42%), whereas nucleofection was optimal (32%) for porcine cells. For FBs, however, nucleofection resulted in the highest transfection rates in human (46%) and porcine (60%) FBs. For specific epidermal cell studies, Fugene HD was the preferred gene transfer method, whereas Effectene appeared to be the optimal reagent for pro-angiogenic studies. Nucleofection in combination with FBs is the best combination to achieve the highest overall transfection rate and is thus the optimal combination for use in ex vivo gene transfer strategies of wound healing or skin tissue engineering.status: publishe

Integration of Blood Outgrowth Endothelial Cells in Dermal Fibroblast Sheets Promotes Full Thickness Wound Healing

Vascularization is the cornerstone of wound healing. We introduced human blood outgrowth endothelial cells (hBOEC) in a self-assembled human dermal fibroblast sheet (hDFS), intended as a tissue-engineered dermal substitute with inherent vascular potential. hBOEC were functionally and molecularly different from early endothelial progenitor cells and human umbilical vein endothelial cells (HUVEC). hBOEC alone, unlike HUVEC, efficiently revascularized and re-oxygenated the wound bed, both by active incorporation into new vessels and by trophic stimulation of host angiogenesis in a dose-dependent manner. Furthermore, hBOEC alone, but not HUVEC, accelerated epithelial coverage and matrix organization of the wound bed. In addition, integration of hBOEC in hDFS not only further improved vascularization, epithelial coverage and matrix organization but also prevented excessive wound contraction. In vitro analyses with hBOEC, fibroblasts and keratinocytes revealed that these effects were both due to growth factor crosstalk and to short cutting hypoxia. Among multiple growth factors secreted by hBOEC, placental growth factor mediated at least in part the beneficial effects on keratinocyte migration and proliferation. Overall, this combined tissue engineering approach paves the way for clinical development of a fully autologous vascularized dermal substitute for patients with large skin defects that do not heal properly. STEM CELLS 2010;28:1165-1177status: publishe

Multipotent Adult Progenitor Cells Support Lymphatic Regeneration at Multiple Anatomical Levels during Wound Healing and Lymphedema

Lymphatic capillary growth is an integral part of wound healing, yet, the combined effectiveness of stem/progenitor cells on lymphatic and blood vascular regeneration in wounds needs further exploration. Stem/progenitor cell transplantation also emerged as an approach to cure lymphedema, a condition caused by lymphatic system deficiency. While lymphedema treatment requires lymphatic system restoration from the capillary to the collector level, it remains undetermined whether stem/progenitor cells support a complex regenerative response across the entire anatomical spectrum of the system. Here, we demonstrate that, although multipotent adult progenitor cells (MAPCs) showed potential to differentiate down the lymphatic endothelial lineage, they mainly trophically supported lymphatic endothelial cell behaviour in vitro. In vivo, MAPC transplantation supported blood vessel and lymphatic capillary growth in wounds and restored lymph drainage across skin flaps by stimulating capillary and pre-collector vessel regeneration. Finally, human MAPCs mediated survival and functional reconnection of transplanted lymph nodes to the host lymphatic network by improving their (lymph)vascular supply and restoring collector vessels. Thus, MAPC transplantation represents a promising remedy for lymphatic system restoration at different anatomical levels and hence an appealing treatment for lymphedema. Furthermore, its combined efficacy on lymphatic and blood vascular growth is an important asset for wound healing

A new large gomphodont from the Triassic of South Africa and its implications for Gondwanan biostratigraphy

A partial skull (BP/1/7976) of a very large cynodont from the Middle Triassic Cynognathus Assemblage Zone (Cricodon-Ufudocyclops subzone) of South Africa is described. The specimen represents a new gomphodont taxon, Impidens hancoxi, gen. et sp. nov., diagnosed by five sectorial teeth constituting just over half of the length of the upper postcanine tooth row, and enlarged canine and incisor teeth. BP/1/8123, a skull fragment also from the Cricodon-Ufudocyclops subzone, and AMNH FARB 24421, a partial skull from the upper Fremouw Formation of Antarctica, are also referred to the new species. The presence of this taxon in both the upper Fremouw Formation and Cricodon-Ufudocyclops subzone strengthens evidence of biostratigraphic correlation between these units. Impidens hancoxi, with an inferred skull length of up to 460 mm, was a large-bodied and likely omnivorous gomphodont, and may have played the role of apex predator within the tetrapod fauna of the Cricodon-Ufudocyclops subzone.Fil: Tolchard, Frederick. University of the Witwatersrand; SudáfricaFil: Kammerer, Christian F.. North Carolina Museum Of Natural Sciences; Estados UnidosFil: Butler, Richard J.. University Of Birmingham; Reino UnidoFil: Hendrickx, Christophe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Benoit, Julien. University of the Witwatersrand; SudáfricaFil: Abdala, Nestor Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Choiniere, Jonah N.. University of the Witwatersrand; Sudáfric

Multicenter Bonding in Ditetracyanoethylene Dianion: A Simple Aromatic Picture in Terms of Three-Electron Bonds

The nature of the multicenter, long bond in ditetracyanoethylene dianion complex [TCNE]₂^2– is elucidated using high level <i>ab initio</i> Valence Bond (VB) theory coupled with Quantum Monte Carlo (QMC) methods. This dimer is the prototype of the general family of pancake-bonded dimers with large interplanar separations. Quantitative results obtained with a compact wave function in terms of only six VB structures match the reference CCSD­(T) bonding energies. Analysis of the VB wave function shows that the weights of the VB structures are not compatible with a covalent bond between the π* orbitals of the fragments. On the other hand, these weights are consistent with a simple picture in terms of two resonating bonding schemes, one displaying a pair of interfragment three-electron σ bonds and the other displaying intrafragment three-electron π bonds. This simple picture explains at once (1) the long interfragment bond length, which is independent of the countercations but typical of three-electron (3-e) CC σ bonds, (2) the interfragment orbital overlaps which are very close to the theoretical optimal overlap of 1/6 for a 3-e σ bond, and (3) the unusual importance of dynamic correlation, which is precisely the main bonding component of 3-e bonds. Moreover, it is shown that the [TCNE]₂^2– system is topologically equivalent to the square C₄H₄^2– dianion, a well-established aromatic system. To better understand the role of the cyano substituents, the unsubstituted diethylenic Na⁺₂[C₂H₄]₂^2– complex is studied and shown to be only metastable and topologically equivalent to a rectangular C₄H₄^2– dianion, devoid of aromaticity

The BCCM/ULC collection to conserve the biodiversity and explore the applied potential of Polar cyanobacteria

In the Polar Regions, Cyanobacteria represent key primary producers and are the main drivers of the food webs in a wide range of aquatic to terrestrial habitats. For example, they build benthic microbial mats in lakes and soil crusts in terrestrial biotopes. They may present interesting features to survive freeze/thaw cycles, seasonally contrasted light intensities, high UV radiations, dessication and other stresses. The BCCM/ULC public collection funded by the Belgian Science Policy Office since 2011 aims to gather a representative portion of the polar cyanobacterial diversity with different ecological origins (limnetic mats, soil crusts, cryoconites, endoliths…). It makes it available for researchers to study the taxonomy, evolution, adaptations to harsh environmental conditions, and genomic make-up. It presently includes 226 cyanobacterial strains, with 119 being of Antarctic origin (catalogue: http://bccm.belspo.be/catalogues/ulc-catalogue-search). An ISO 9001 certificate was obtained for the public deposition and distribution of strains, as part of the multi-site certification for the BCCM consortium. The morphological identification shows that the strains belong to the orders Synechococcales, Oscillatoriales, Pleurocapsales, Chroococcidiopsidales and Nostocales. The 16S rRNA and ITS sequences of the strains are being characterized. Our results show that the Antarctic strains are positioned into 25 OTUs (sequences with > 97,5% 16S rRNA similarity), and thus, represent a quite large diversity. In addition, cyanobacteria are known to produce a wide range of secondary metabolites (e.g. alkaloids, cyclic and linear peptides, polyketides) with bioactive potential. Among these bioactive metabolites, some display antibiotic, anticancer or antifungal effects. In collaboration with the BCCM/IHEM collection of biomedical fungi, a screening of cyanobacterial strains from BCCM/ULC was performed in order to discover potential new antifungal drugs. The analysis of a first set of methanol extracts from 15 different strains put in evidence the antifungal activity of a Phormidium priestleyi isolate. The latter remains active up to 0.5% (v/v) of fungal culture and was able to inhibit the growth of various fungal species among Candida, Cryptococcus, Aspergillus, and Penicillium. The raw extract was subjected to HPLC and a fraction containing the active molecule was obtained. This molecule appeared to be a thermostable hydrophobic compound. Moreover, in vitro toxicological analyses suggest that the compound has a general cytotoxic effect that could be inhibited by the mammalian metabolism. Further analyses are needed to identify the molecule and to determine if it could be a candidate for a new antifungal drug. In summary, the BCCM/ULC public collection serves as a Biological Resource Centre to conserve ex situ and document the biodiversity of polar cyanobacteria, as well as a repository for discovery of novel bioactive compounds.BCCM/ULC collection of cyanobacteri

Epidemiología de la neumonía adquirida en la comunidad que requiere hospitalización en personas de 65 años y más. Factores de riesgo y factores asociados al reingreso

La neumonía es un proceso inflamatorio agudo del parénquima pulmonar que se manifiesta por signos y síntomas de infección respiratoria acompañados por un nuevo infiltrado en una radiografía de tórax. Cuando afecta a la población no ingresada en un hospital se denomina neumonía adquirida en la comunidad (NAC). La NAC es una causa de morbilidad y mortalidad importante que afecta especialmente a los menores de 5 años y a las personas de 65 años y más. Según datos de las Naciones Unidas, en 2017 las personas de 65 años y más representaba el 8,29% de la población mundial y Europa acumula el porcentaje más alto de personas en este grupo de edad, el 17,59%. La incidencia de la NAC en países europeos es variable. Sin embargo, la incidencia de casos aumenta con la edad en todos los países y aproximadamente el 45% de todos los casos de NAC ocurren en pacientes de 65 años o más. En España, la recomendación actual es vacunar con vacuna antineumocócica polisacarida 23 valente a las personas de 65 años y más, administrando una dosis de recuerdo al menos 5 años después de la dosis anterior si había recibido la vacuna antes de los 65 años. Se recomienda la pauta secuencial de administración de vacuna antineumocócica conjugada 13 valente y vacuna antineumocócica polisacarida 23 valente separada por un intervalo óptimo de 12 meses y mínimo de al menos 8 semanas en personas que presenten inmunodepresión. Los OBJETIVOS del estudio son: 1. Determinar los factores de riesgo asociados al reingreso hospitalario en los 30 días posteriores al alta por NAC en personas de 65 años y más. 2. Evaluar la capacidad predictiva de la mortalidad por NAC mediante la combinación del Índice de Barthel y del Índice de Severidad de la Neumonía en personas de 65 años y más hospitalizadas. 3. Determinar los factores asociados a la cobertura de vacuna antineumocócica polisacárida 23-valente en personas de 65 años y más hospitalizadas por causas no relacionadas con neumonía, enfermedad respiratoria aguda o síndrome gripal en España. 4. Estimar la efectividad de la vacunación antineumocócica polisacárida 23 valente para prevenir la hospitalización por NAC en personas de 65 años y más y para prevenir las formas graves de NAC (ingreso en UCI y muerte) en personas hospitalizadas de 65 años y más. CONCLUSIONES: En pacientes de 65 años y más hospitalizados por NAC la tasa de reingreso en los 30 días posteriores al alta fue moderada, asociándose a factores predisponentes relacionados con el tipo de atención al paciente. La evaluación combinada del Pneumonia Severity Index y del Índice de Barthel predice con mayor precisión la mortalidad que la aplicación de cada índice por separado. La cobertura de vacunación antineumocócica en las personas de 65 años y más hospitalizadas por motivos distintos a la neumonía, enfermedad respiratoria aguda o síndrome gripal es baja y deberían establecerse estrategias para aumentar dicha cobertura. La vacunación con la vacuna antineumocócica polisacarida 23 mostró una efectividad modesta para evitar la hospitalización por NAC en las personas de 65 años y más que aumentó hasta el 40,9% para prevenir ingreso a UCI o muerte. Para valorar la conveniencia de posibles cambios en las recomendaciones de vacunación de las personas de 65 años y más es fundamental mantener una vigilancia continua de los serotipos causantes de la enfermedad neumocócica en esta población.INTRODUCTION: Community-acquired pneumonia (CAP) is a frequent, potentially serious disease in people aged ≥65years and one of the leading causes of hospitalization and mortality worldwide in this age group, in whom recovery from an episode of CAP is predictive of increased mortality in subsequent years. The incidence of CAP differs between European countries due to variations in age distribution, the introduction of vaccination programs and the clinical guidelines used. However, the incidence of cases and hospitalizations increases with age in all countries. Vaccination of the elderly is an important factor in limiting the impact of pneumonia in the community. OBJECTIVES: 1. Determine factors associated with 30-day readmission in patients with CAP. 2. Assess the predictive ability of community-acquired pneumonia mortality by combining the Barthel Index and Pneumonia Severity Index in patients aged ≥65years. 3. To determine the factors associated with the 23-valent polysaccharide pneumococcal vaccine coverage in people aged ≥65years hospitalized for causes unrelated to pneumonia, acute respiratory disease or influenza-like syndrome in Spain. 4. Estimate the effect of pneumococcal polysaccharide vaccination in preventing CAP hospitalization in hospitalized subjects aged ≥65years and reducing the risk of severe and fatal outcomes in CAP hospitalized subjects aged ≥65years. CONCLUSIONS: Rehospitalisation was associated with preventable and non-preventable factors. The use of a bimodal model to assess CAP mortality (PSI+BI) provides more accurate prognostic information than the use of each index separately. Pneumococcal vaccination coverage of hospitalized elderly people is low. The elderly need to be targeted about pneumococcal vaccination and activities that encourage healthcare workers to proactively propose vaccination might be useful. PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP