Renal microvascular assembly and repair: power and promise of molecular definition.

Developmental assembly of the renal microcirculation is a precise and coordinated process now accessible to experimental scrutiny. Although definition of the cellular and molecular determinants is incomplete, recent findings have reframed concepts and questions about the origins of vascular cells in the glomerulus and the molecules that direct cell recruitment, specialization and morphogenesis. New findings illustrate principles that may be applied to defining critical steps in microvascular repair following glomerular injury. Developmental assembly of endothelial, mesangial and epithelial cells into glomerular capillaries requires that a coordinated, temporally defined series of steps occur in an anatomically ordered sequence. Recent evidence shows that both vasculogenic and angiogenic processes participate. Local signals direct cell migration, proliferation, differentiation, cell-cell recognition, formation of intercellular connections, and morphogenesis. Growth factor receptor tyrosine kinases on vascular cells are important mediators of many of these events. Cultured cell systems have suggested that basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) promote endothelial cell proliferation, migration or morphogenesis, while genetic deletion experiments have defined an important role for PDGF beta receptors and platelet-derived growth factor (PDGF) B in glomerular development. Receptor tyrosine kinases that convey non-proliferative signals also contribute in kidney and other sites. The EphB1 receptor, one of a diverse class of Eph receptors implicated in neural cell targeting, directs renal endothelial migration, cell-cell recognition and assembly, and is expressed with its ligand in developing glomeruli. Endothelial TIE2 receptors bind angiopoietins (1 and 2), the products of adjacent supportive cells, to signals direct capillary maturation in a sequence that defines cooperative roles for cells of different lineages. Ultimately, definition of the cellular steps and molecular sequence that direct microvascular cell assembly promises to identify therapeutic targets for repair and adaptive remodeling of injured glomeruli.

Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair

Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient.

Norm enforcement in the city revisited: An international field experiment of altruistic punishment, norm maintenance, and broken windows

In laboratory experiments, people are willing to sanction norms at a cost—a behavioral tendency called altruistic punishment. However, the degree to which these findings can be generalized to real-world interactions is still debated. Only a small number of field experiments have been conducted, and initial results suggest that punishment is less frequent outside of the lab. This study replicates one of the first field experiments on altruistic punishment and builds ties to research on norm compliance and the broken windows theory. The original study addressed the enforcement of the anti-littering norm in Athens. We replicate this study in Bern, Zurich, and New York City. As an extension, we investigate how the experimental context (clean vs littered) impacts social norm enforcement. As a second extension, we investigate how opportunity structure impacts the maintenance of the anti-littering norm. Findings indicate that norms are universally enforced, although significantly less than in the standard laboratory experiment,and that enforcement is significantly more common in Switzerland than in New York. Moreover, individuals prefer more subtle forms of enforcement to direct punishment. We also find that enforcement is less frequent in littered than in clean contexts, suggesting that broken windows might not only foster deviant behavior but also weaken informal social control. Finally, we find that opportunity structure can encourage people to maintain norms, as indicated by the fact that people are more likely to voluntarily pick up litter when it is closer to a trash bin.

[Gerodontic consultation service for hospitalized geriatric patients: diagnosis and therapy (II)]

The aim of the study was to report on oral, dental and prosthetic conditions as well as therapeutic measures for temporarily institutionalized geriatric patients. The patients were referred to the dentist since dental problems were observed by the physicians or reported by the patients themselves. This resulted in a selection among the geriatric patients; but they are considered to be representative for this segment of patients exhibiting typical signs of undertreatment. The main problem was the poor retention of the prosthesis, which was associated to insufficient masticatory function and poor nutrition status. Forty-seven percent of the patients were edentulous or had maximally two radicular rests out of function. Altogether 70% of the maxillary and 51% of the mandibular jaws exhibited no more teeth. Eighty-nine percent of the patients had a removable denture, and it was observed that maxillary dentures were regularly worn in contrast to mandibular dentures. The partially edentate patients had a mean number of ten teeth, significantly more in the manidublar than maxillary jaw. Treatment consisted mainly in the adaptation and repair of dentures, tooth extractions and fillings. Only few appointments (mostly two) were necessary to improve the dental conditions, resulting in low costs. Patients without dentures or no need for denture repair generated the lowest costs. Slightly more visits were necessary for patients with dementia and musculoskeletal problems. The present findings show that regular maintenance care of institutionalized geriatric patients would limit costs in a long-term perspective, improve the oral situation and reduce the need for invasive treatment.

Repair of Annulus fibrosus with Genipin-enhanced Fibrin Hydrogel and silk membrane- fleece

Introduction Low back pain is often caused by a trauma causing disc herniation and /or disc degeneration. Although there are some promising approaches for nucleus pulposus repair, the inner tissue of the intervertebral disc (IVD) so far no treatment or repair is available for annulus fibrosus (AF) injuries. Here we aimed to develop a new method to seal and repair AF injuries by using a silk fleece composite and a genipin enhanced hydrogel. Methods Bovine (b) IVDs were harvested under aseptic conditions and kept in free swelling conditions for 24h in high-glucose DMEM containing 5% bovine serum for equilibration (1). A circular 2mm biopsy punch (Polymed Medical Center, Switzerland) was used to form a reproducible defect in the AF. For filling the defect and keeping the silk composite in place a human-derived fibrin gel (Baxter Tisseel, Switzerland) enhanced with 4.2mg/ml of the cross linker genipin (Wako Chemicals GmbH, Germany) was used. The silk composite consists of a mesh- and a membrane side (Spintec Engineering GmbH, Germany); the membrane is facing outwards to form a seal. bIVDs were cultured in vitro for 14 days either under dynamic load in a custom-built bioreactor under physiological conditions (0.2MPa load and ±2° torsion at 0.2Hz for 8h/day) or static diurnal load of 0.2MPa (2). At the end of culture discs were checked for seal failure, disc height, metabolic activity, cell death by necrosis (LDH assay), DNA content and glycosaminoglycan content. Results Silk composite maintained its position throughout the 14 days of culture under loaded conditions. Although repaired discs performed slightly lower in cell activity, DNA and GAG content were in the range of the control. Also LDH resulted in similar values compared to control discs (Fig 1). Height loss in repaired discs was in the same range as for static diurnal loaded control samples. For dynamically loaded samples the decrease was comparable to the injured, unrepaired discs. Fig 1 LDH of repaired discs compared to control disc after 24h in free swelling conditions for equilibration and first three loading cycles. Conclusions Silk-genipin-fibrin reinforced hydrogel is a promising approach to close AF defects as tested by two degree of freedom loading. In further experiments cytocompatibility of genipin has to be investigated. References 1. Chan SC, Gantenbein-Ritter B. Preparation of intact bovine tail intervertebral discs for organ culture. J Vis Exp 2012, Feb 2;60(60):e3490. 2. Walser J, Ferguson SJ, Gantenbein-Ritter B. Design of a mechanical loading device to culture intact bovine caudal motional segments of the spine under twisting motion. In: Davies J, editors. Replacing animal models: a practical guide to creating and using biomimetic alternatives. Chichester, UK: John Wiley & Sons, Ltd.; 2012. p. 89-105. Acknowledgements This project is funded by the Gerbert Rüf Stiftung project # GRS-028/13 and the Swiss National Science Project SNF #310030_153411.

Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma

Lung cancer is one of the leading causes of cancer-related deaths in the world. Although the origin still remains to be resolved, a prevailing hypothesis implies the involvement of cancer stem cells (CSCs) responsible for tumor initiation, maintenance, and progression. Embryonic stem cell marker, OCT4, encoding the spliced variants OCT4A and OCT4B, has recently been shown to have a dual role; as a potential adult stem cell marker and as a CSC marker in germline and somatic tumors.

The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development

OBJECTIVE: During postnatal development, mammalian articular cartilage acts as a surface growth plate for the underlying epiphyseal bone. Concomitantly, it undergoes a fundamental process of structural reorganization from an immature isotropic to a mature (adult) anisotropic architecture. However, the mechanism underlying this structural transformation is unknown. It could involve either an internal remodelling process, or complete resorption followed by tissue neoformation. The aim of this study was to establish which of these two alternative tissue reorganization mechanisms is physiologically operative. We also wished to pinpoint the articular cartilage source of the stem cells for clonal expansion and the zonal location of the chondrocyte pool with high proliferative activity. METHODS: The New Zealand white rabbit served as our animal model. The analysis was confined to the high-weight-bearing (central) areas of the medial and lateral femoral condyles. After birth, the articular cartilage layer was evaluated morphologically at monthly intervals from the first to the eighth postnatal month, when this species attains skeletal maturity. The overall height of the articular cartilage layer at each juncture was measured. The growth performance of the articular cartilage layer was assessed by calcein labelling, which permitted an estimation of the daily growth rate of the epiphyseal bone and its monthly length-gain. The slowly proliferating stem-cell pool was identified immunohistochemically (after labelling with bromodeoxyuridine), and the rapidly proliferating chondrocyte population by autoradiography (after labelling with (3)H-thymidine). RESULTS: The growth activity of the articular cartilage layer was highest 1 month after birth. It declined precipitously between the first and third months, and ceased between the third and fourth months, when the animal enters puberty. The structural maturation of the articular cartilage layer followed a corresponding temporal trend. During the first 3 months, when the articular cartilage layer is undergoing structural reorganization, the net length-gain in the epiphyseal bone exceeded the height of the articular cartilage layer. This finding indicates that the postnatal reorganization of articular cartilage from an immature isotropic to a mature anisotropic structure is not achieved by a process of internal remodelling, but by the resorption and neoformation of all zones except the most superficial (stem-cell) one. The superficial zone was found to consist of slowly dividing stem cells with bidirectional mitotic activity. In the horizontal direction, this zone furnishes new stem cells that replenish the pool and effect a lateral expansion of the articular cartilage layer. In the vertical direction, the superficial zone supplies the rapidly dividing, transit-amplifying daughter-cell pool that feeds the transitional and upper radial zones during the postnatal growth phase of the articular cartilage layer. CONCLUSIONS: During postnatal development, mammalian articular cartilage fulfils a dual function, viz., it acts not only as an articulating layer but also as a surface growth plate. In the lapine model, this growth activity ceases at puberty (3-4 months of age), whereas that of the true (metaphyseal) growth plate continues until the time of skeletal maturity (8 months). Hence, the two structures are regulated independently. The structural maturation of the articular cartilage layer coincides temporally with the cessation of its growth activity - for the radial expansion and remodelling of the epiphyseal bone - and with sexual maturation. That articular cartilage is physiologically reorganized by a process of tissue resorption and neoformation, rather than by one of internal remodelling, has important implications for the functional engineering and repair of articular cartilage tissue.

Analyzing Software Evolution through Feature Views

Features encapsulate the domain knowledge of a software system and thus are valuable sources of information for a reverse engineer. When analyzing the evolution of a system, we need to know how and which features were modified to recover both the change intention and its extent, namely which source artifacts are affected. Typically, the implementation of a feature crosscuts a number of source artifacts. To obtain a mapping between features to the source artifacts, we exercise the features and capture their execution traces. However this results in large traces that are difficult to interpret. To tackle this issue we compact the traces into simple sets of source artifacts that participate in a feature's runtime behavior. We refer to these compacted traces as feature views. Within a feature view, we partition the source artifacts into disjoint sets of characterized software entities. The characterization defines the level of participation of a source entity in the features. We then analyze the features over several versions of a system and we plot their evolution to reveal how and hich features were affected by changes in the code. We show the usefulness of our approach by applying it to a case study where we address the problem of merging parallel development tracks of the same system.

An analysis of the spatial and temporal patterns of highly pathogenic avian influenza occurrence in Vietnam using national surveillance data

The objectives of this study were to describe the spatio-temporal pattern of an epidemic of highly pathogenic avian influenza (HPAI) in Vietnam and to identify potential risk factors for the introduction and maintenance of infection within the poultry population. The results indicate that during the time period 2004–early 2006 a sequence of three epidemic waves occurred in Vietnam as distinct spatial and temporal clusters. The risk of outbreak occurrence increased with a greater percentage of rice paddy fields, increasing domestic water bird and chicken density. It increased with reducing distance to higher population density aggregations, and in the third epidemic wave with increasing percentage of aquaculture. The findings indicate that agri-livestock farming systems involving domestic water birds and rice production in river delta areas are important for the maintenance and spread of infection. While the government’s control measures appear to have been effective in the South and Central parts of Vietnam, it is likely that in the North of Vietnam the vaccination campaign led to transmission of infection which was subsequently brought under control.

A functional model for adult stem cells in epithelial tissues

Tissue turnover, regeneration, and repair take place throughout life. Stem cells are key players in these processes. The characteristics and niches of the stem cell populations in different tissues, and even in related tissues, vary extensively. In this review, stem cell differentiation and stem cell contribution to tissue maintenance and regeneration is compared in the epithelia of the skin, the cornea, the lung, and the intestine. A hierarchical model for adult stem cells is proposed, based on the potency of stem cell subpopulations in a specific tissue. The potency is defined in terms of the maintenance, the repair, and the regeneration of the tissue. The niche supplies cues to maintain the specific stem cell potency.

Removable dentures with implant support in strategic positions followed for up to 8 years

PURPOSE: The aim of this study was to analyze prosthetic maintenance in partially edentulous patients with removable prostheses supported by teeth and strategic implants. MATERIALS AND METHODS: Sixty patients with removable partial prostheses and combined tooth-implant support were identified within the time period from 1998 to 2006. One group consisted of 42 patients (planned group) with a reduced residual dentition and in need of removable partial dentures (RPDs) or overdentures in the maxilla and/or mandible. They were admitted consecutively for treatment. Due to missing teeth in strategic important positions, one or two implants were placed to improve symmetrical denture support and retention. The majority of residual teeth exhibited an impaired structural integrity and therefore were provided with root copings for denture retention. A few vital teeth were used for telescopic crowns. The anchorage system for the strategic implants was selected accordingly. A second group of 18 patients (repair group) wearing RPDs with the loss of one abutment tooth due to biologic or mechanical failure was identified. These abutment teeth were replaced by 21 implants, and patients continued to wear their original prostheses. The observation time for planned and repair groups was 12 months to 8 years. All patients followed a regular maintenance schedule. Technical or biologic complications with supporting teeth or implants and prosthetic service were registered regularly. RESULTS: Three maxillary implants were lost after loading and three roots with copings had to be removed. Biologic problems included caries and periodontal/peri-implant infection with a significantly higher incidence in the repair group (P < .05). Technical complications with the dentures were rather frequent in both groups, mostly related to the anchorage system (matrices) of root copings and implants. Maintenance and complications were observed more frequently in the first year after delivery of the denture than in the following 3 years (P < .05). No denture had to be remade. CONCLUSIONS: The placement of a few implants allows for maintaining a compromised residual dentition for support of RPDs. The combination of root and implant support facilitates treatment planning and enhances designing the removable denture. It also proves to be a practical rescue method. Technical problems with the anchorage system were frequent, particularly in the first year after delivery of the dentures.

Body fluids and salt metabolism - Part I

ABSTRACT: There is a high frequency of diarrhea and vomiting in childhood. As a consequence the focus of the present review is to recognize the different body fluid compartments, to clinically assess the degree of dehydration, to know how the equilibrium between extracellular fluid and intracellular fluid is maintained, to calculate the effective blood osmolality and discuss both parenteral fluid requirments and repair.