An update on the aetiology of orofacial clefts

Objective. To review recent data on the aetiology of cleft lip and palate. Data sources. MEDLINE literature search (1986-2003). Study selection. Literature and data on aetiology of cleft lip and palate using the following key words: 'cleft lip', 'cleft palate', 'aetiology', and 'genetics'. Data extraction. Relevant information and data were reviewed by the authors. Data synthesis. Cleft lip and palate is one of the most common types of congenital malformation. The aetiology seems complex, but genetics plays a major role. Recently several genes causing syndromic cleft lip and palate have been discovered. Three of them-namely T-box transcription factor-22 (TBX22), poliovirus receptor like-1 (PVRL1), and interferon regulatory factor-6 (IRF6)-are responsible for causing X-linked cleft palate, cleft lip/palate-ectodermal dysplasia syndrome, and Van der Woude's and popliteal pterygium syndromes, respectively; they are also implied in non-syndromic cleft lip and palate. The nature and function of these genes vary widely, illustrating high vulnerability within the craniofacial developmental pathways. The aetiological complexity of non-syndromic cleft lip and palate is also exemplified by the large number of candidate genes and loci. Conclusions. The aetiology of non-syndromic cleft lip and palate is still largely unknown, but mutations in candidate genes have already been identified in a small proportion of cases of non-syndromic cleft lip and palate. Determining the relative risk of cleft lip and palate, on the basis of genetic background and environmental influence, including smoking, alcohol use, and dietary factors, will aid in genetic counselling and the development of future preventive measures.published_or_final_versio

Indian hedgehog: A mechanotransduction mediator in condylar cartilage

Indian hedgehog (Ihh) is a critical mediator transducing mechanical signals to stimulate chondrocyte proliferation. To clarify the cellular signal transduction pathway that senses and converts mechanical signals into tissue growth in mandibular condyle, we evaluated Ihh expression and its relation to the kinetics of replicating mesenchymal cells in condylar cartilage during natural growth and mandibular advancement. Thirty-five-day-old Sprague-Dawley rats were fitted with functional appliances. Experimental animals with matched controls were doubly labeled with iododeoxyuridine and bromodeoxyuridine so that we could evaluate the cycles of the proliferative mesenchymal cells. Mandibular advancement triggered Ihh expression in condylar cartilage. A higher level of Ihh expression coincided with the increase of the replicating mesenchymal cells' population and the shortening of the turnover time. These findings suggested that Ihh acts as a mediator of mechanotransduction that converts mechanical signals resulting from anterior mandibular displacement to stimulate cellular proliferation in condylar cartilage.published_or_final_versio

PTHrP regulates chondrocyte maturation in condylar cartilage

PTHrP is a key factor regulating the pace of endochondral ossification during skeletal development. Mandibular advancement solicits a cascade of molecular responses in condylar cartilage. However, the pace of cellular maturation and its effects on condylar growth are still unknown. The purpose of this study was to evaluate the pattern of expression of PTHrP and correlate it to cellular dynamics of chondrocytes in condylar cartilage during natural growth and mandibular advancement. We fitted 35-day-old Sprague-Dawley rats with functional appliances. Experimental animals with matched controls were labeled with bromodeoxyuridine 3 days before their death, so that mesenchymal cell differentiation could be traced. Mandibular advancement increased the number of differentiated chondroblasts and subsequently increased the cartilage volume. Higher levels of PTHrP expression in experimental animals coincided with the slowing of chondrocyte hypertrophy. Thus, mandibular advancement promoted mesenchymal cell differentiation and triggered PTHrP expression, which retarded their further maturation to allow for more growth.published_or_final_versio

The effect of demineralized bone matrix on the healing of intramembranous bone grafts in rabbit skull defects

A clinical dilemma exists regarding the type of bone that should be used to replace diseased or traumatized osseous tissue. Oral, plastic, and orthopedic surgeons normally implant viable mineralized endochondral (EC) autografts or demineralized EC allografts. A few clinicians have recognized the disadvantages of using EC bone in craniofacial surgery and advocated the replacement of intramembranous (IM) bone with healthy IM bone. However, controversy and uncertainty surround our understanding of these matrices to induce bone formation. Recent studies have advocated the use of other materials with osteoinductive properties, such as demineralized bone matrix (DBM). The proposed delivery system used in this study included IM bone grafts, DBM, and fixation of the IM bone graft. The purpose of this work was to gain further insights into the mechanism of healing of IM bone, in both the presence and the absence of DBM, and to compare the healing of IM bone grafts with that of DBM alone. Critical-sized (10 × 5 mm), full-thickness bony defects in rabbit parietal bone, devoid of periosteum, were filled with IM bone graft (mandible) alone, demineralized cortical bone matrix (DBM) alone, or combined DBM-IM bone graft, or were left unfilled. Histologic changes were examined 14 days later. The IM bone graft healed through IM ossification with no intermediate cartilage stage. DBM and composite DBM-IM healed through an EC ossification with an intermediate cartilage stage. It is hypothesized that the role of the IM graft is to induce neovascularization into the defect site, and that the undifferentiated mesenchymal cells in the perivascular region of the new blood vessels are induced by the bone morphogenetic protein(s) in the DBM into bone-forming cells.published_or_final_versio

Electronic structure and chemical bonding in Ti2AlC investigated by soft x-ray emission spectroscopy

The electronic structure of the nanolaminated transition metal carbide Ti2AlC has been investigated by bulk-sensitive soft x-ray emission spectroscopy. The measured Ti L, C K and Al L emission spectra are compared with calculated spectra using ab initio density-functional theory including dipole matrix elements. The detailed investigation of the electronic structure and chemical bonding provides increased understanding of the physical properties of this type of nanolaminates. Three different types of bond regions are identified; the relatively weak Ti 3d - Al 3p hybridization 1 eV below the Fermi level, and the Ti 3d - C 2p and Ti 3d - C 2s hybridizations which are stronger and deeper in energy are observed around 2.5 eV and 10 eV below the Fermi level, respectively. A strongly modified spectral shape of the 3s final states in comparison to pure Al is detected for the buried Al monolayers indirectly reflecting the Ti 3d - Al 3p hybridization. The differences between the electronic and crystal structures of Ti2AlC, Ti3AlC2 and TiC are discussed in relation to the number of Al layers per Ti layer in the two former systems and the corresponding change of the unusual materials properties.Comment: 14 pages, 7 figures; PACS:78.70.En, 71.15.Mb, 71.20.-

Extended Classical Over-Barrier Model for Collisions of Highly Charged Ions with Conducting and Insulating Surfaces

We have extended the classical over-barrier model to simulate the neutralization dynamics of highly charged ions interacting under grazing incidence with conducting and insulating surfaces. Our calculations are based on simple model rates for resonant and Auger transitions. We include effects caused by the dielectric response of the target and, for insulators, localized surface charges. Characteristic deviations regarding the charge transfer processes from conducting and insulating targets to the ion are discussed. We find good agreement with previously published experimental data for the image energy gain of a variety of highly charged ions impinging on Au, Al, LiF and KI crystals.Comment: 32 pages http://pikp28.uni-muenster.de/~ducree

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

BACKGROUND:Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS:Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE:MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured

The persistence of epiphyseal scars in the distal radius in adult individuals

The use of radiographic imaging in the estimation of chronological age facilitates the analysis of structures not visible on gross morphological inspection. Following the completion of epiphyseal fusion, a thin radio-opaque band, the epiphyseal scar, may be observed at the locus of the former growth plate. The obliteration of this feature has previously been interpreted as the final stage of skeletal maturation and consequently has been included as a criterion in several methods of age estimation, particularly from the distal radius. Due to the recommendations relating to age estimation in living individuals, accurate assessment of age from the distal radius is of great importance in human identification; however, the validity of the interpretation of the obliteration of the epiphyseal scar as an age-related process has not been tested. A study was undertaken to assess the persistence of epiphyseal scars in adults between 20 and 50 years of age through the assessment of 616 radiographs of left and right distal radii from a cross-sectional population. This study found that 86 % of females and 78 % of males retained some remnant of the epiphyseal scar in the distal radius. The relationships between chronological age, biological sex and the persistence of the epiphyseal scar were not statistically significant. The findings of this study indicate that the epiphyseal scars may persist in adult individuals until at least 50 years of age. No maximum age should therefore be applied to the persistence of an epiphyseal scar in the distal radius