Bone apposition to a titanium-zirconium alloy implant, as compared to two other titanium-containing implants

Implants made of commercially pure titanium (cpTi) are widely and successfully used in dentistry. For certain indications, diameter-reduced Ti alloy implants with improved mechanical strength are highly desirable. The aim was to compare the osseointegration of titanium-zirconium (TiZr) and cpTi implants with a modified sandblasted and acid-etched (SLActive) surface and with a Ti6Al4V alloy that was sand-blasted and acid-washed. Cylindrical implants with two, 0.75 mm deep, circumferential grooves were placed in the maxilla of miniature pigs and allowed to heal for 1, 2, 4 and 8 weeks. Undecalcified toluidine blue-stained ground sections were produced. Surface topography, area fraction of tissue components, and bone-to-implant contact (BIC) were determined. All materials showed significantly different surface roughness parameters. The amount of new bone within the implant grooves increased over time, without significant differences between materials. However, BIC values were significantly related to the implant material and the healing period. For TiZr and cpTi implants, the BIC increased over time, reaching values of 59.38 % and 76.15 % after 2 weeks, and 74.50 % and 84.67 % after 8 weeks, respectively. In contrast, the BIC for Ti6Al4V implants peaked with 42.29 % after 2 weeks followed by a decline to 28.60 % at 8 weeks. Significantly more surface was covered by multinucleated giant cells on Ti6Al4V implants after 4 and 8 weeks. In conclusion, TiZr and cpTi implants showed faster osseointegration than Ti6Al4V implants. Both chemistry and surface topography might have influenced the results. The use of diameter-reduced TiZr implants in more challenging clinical situations warrants further documentation in long-term clinical studies.

Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: influence of microenvironment, tissue origin and growth factor

Mesenchymal stromal cells (MSCs), which reside within various tissues, are utilized in the engineering of cartilage tissue. Dexamethasone (DEX)--a synthetic glucocorticoid--is almost invariably applied to potentiate the growth-factor-induced chondrogenesis of MSCs in vitro, albeit that this effect has been experimentally demonstrated only for transforming-growth-factor-beta (TGF-β)-stimulated bone-marrow-derived MSCs. Clinically, systemic glucocorticoid therapy is associated with untoward side effects (e.g., bone loss and increased susceptibility to infection). Hence, the use of these agents should be avoided or limited. We hypothesize that the influence of DEX on the chondrogenesis of MSCs depends upon their tissue origin and microenvironment [absence or presence of an extracellular matrix (ECM)], as well as upon the nature of the growth factor. We investigated its effects upon the TGF-β1- and bone-morphogenetic-protein 2 (BMP-2)-induced chondrogenesis of MSCs as a function of tissue source (bone marrow vs. synovium) and microenvironment [cell aggregates (no ECM) vs. explants (presence of a natural ECM)]. In aggregates of bone-marrow-derived MSCs, DEX enhanced TGF-β1-induced chondrogenesis by an up-regulation of cartilaginous genes, but had little influence on the BMP-2-induced response. In aggregates of synovial MSCs, DEX exerted no remarkable effect on either TGF-β1- or BMP-2-induced chondrogenesis. In synovial explants, DEX inhibited BMP-2-induced chondrogenesis almost completely, but had little impact on the TGF-β1-induced response. Our data reveal that steroids are not indispensable for the chondrogenesis of MSCs in vitro. Their influence is context dependent (tissue source of the MSCs, their microenvironment and the nature of the growth-factor). This finding has important implications for MSC based approaches to cartilage repair.

Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium

We present a microfluidic epithelial wound-healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow-focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system, a technique that is reported here for the first time. We demonstrate that alveolar epithelial cells cultured in a microfluidic environment preserve their phenotype before and after wounding. In addition, we report a wound-healing benefit induced by addition of HGF to the cell culture medium (19.2 vs. 13.5 μm h(-1) healing rate).

Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis

About 2·1 million pregnant women have active syphilis every year. Without screening and treatment, 69% of these women will have an adverse outcome of pregnancy. The objectives of this study were to review the literature systematically to determine the effectiveness of screening interventions to prevent congenital syphilis and other adverse pregnancy outcomes.

New-onset epilepsy: considerations for initial and follow-up MRI to detect brain tumor

Seizures are often the presenting symptoms of a cerebral tumor and may precede its diagnosis by many years. The article under evaluation searched two large English registries for patients admitted for new-onset epilepsy. The risk of subsequently being diagnosed with a malignant brain tumor was found to be 26-fold higher compared with controls, persisted over many years and was accentuated in young patients. Recently, surgical advances have led to a significant decrease in surgical morbidities, making surgery the first treatment option for gliomas, especially low-grade gliomas. This paradigm shift warrants a consequent diagnostic workup (MRI) in patients at risk for low-grade glioma - that is, patients with new-onset epilepsy. The study is discussed in the context of the ongoing debate on neuroimaging after new-onset epilepsy.

Macrocerebellum: Significance and Pathogenic Considerations

Macrocerebellum is a rare finding characterized by an abnormally large cerebellum. Only few patients with a syndromal or isolated macrocerebellum have been reported so far. This article aims to categorize the magnetic resonance imaging (MRI) findings, quantitate the macrocerebellum by volumetric analysis, characterize the neurological and dysmorphic features and cognitive outcome, and report the results of genetic analyses in children with macrocerebellum. All MR images were qualitatively evaluated for infratentorial and supratentorial abnormalities. Volumetric analysis was performed. Data about neurological and dysmorphic features, outcome, and genetic analysis were collected from clinical histories and follow-up examinations. Five patients were included. Volumetric analysis in three patients confirmed large cerebellar size compared to age-matched controls. MR evaluation showed that thickening of the cortical gray matter of the cerebellar hemispheres is responsible for the macrocerebellum. Additional infratentorial and supratentorial abnormalities were present in all patients. Muscular hypotonia, as well as impaired motor and cognitive development, was found in all patients, with ocular movement disorders in three of five patients. The five patients differed significantly in terms of dysmorphic features and involvement of extracerebral organs. Submicroscopic chromosomal aberrations were found in two patients. Macrocerebellum is caused by thickening of the cortical gray matter of the cerebellar hemispheres, suggesting that cerebellar granule cells may be involved in its development. Patients with macrocerebellum show highly heterogeneous neuroimaging, clinical, and genetic findings, suggesting that macrocerebellum is not a nosological entity, but instead represents the structural manifestation of a deeper, more basic biological disturbance common to heterogeneous disorders.

Diagnostic microchip to assay 3D colony-growth potential of captured circulating tumor cells

Microfluidic technology has been successfully applied to isolate very rare tumor-derived epithelial cells (circulating tumor cells, CTCs) from blood with relatively high yield and purity, opening up exciting prospects for early detection of cancer. However, a major limitation of state-of-the-art CTC-chips is their inability to characterize the behavior and function of captured CTCs, for example to obtain information on proliferative and invasive properties or, ultimately, tumor re-initiating potential. Although CTCs can be efficiently immunostained with markers reporting phenotype or fate (e.g. apoptosis, proliferation), it has not yet been possible to reliably grow captured CTCs over long periods of time and at single cell level. It is challenging to remove CTCs from a microchip after capture, therefore such analyses should ideally be performed directly on-chip. To address this challenge, we merged CTC capture with three-dimensional (3D) tumor cell culture on the same microfluidic platform. PC3 prostate cancer cells were isolated from spiked blood on a transparent PDMS CTC-chip, encapsulated on-chip in a biomimetic hydrogel matrix (QGel™) that was formed in situ, and their clonal 3D spheroid growth potential was assessed by microscopy over one week in culture. The possibility to clonally expand a subset of captured CTCs in a near-physiological in vitro model adds an important element to the expanding CTC-chip toolbox that ultimately should improve prediction of treatment responses and disease progression.

Identifying the best candidate for radical prostatectomy among patients with high-risk prostate cancer

The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial.

Ungual melanoma - controversies in diagnosis and treatment

Ungual melanomas are considered rare, being difficult to diagnose, and having a poor prognosis. The aim of the present study was to discuss the epidemiology, potential causes, treatment options, and outcome of ungual melanomas. In contrast to assumptions in many articles, ungual melanomas are not rare when calculated for the cumulative size of the nail apparatus of both the fingers and toes. The prognosis is not worse than that of melanomas with the same thickness, mitotic rate, or presence of ulceration on other sites. Melanomas of the nail apparatus behave similar to melanomas in other localizations. What makes them enigmatic is the high rate of misdiagnoses and very late diagnoses.