Comparison of theoretical fixation stability of three devices employed in medial opening wedge high tibial osteotomy: a finite element analysis.

BACKGROUND Medial open wedge high tibial osteotomy is a well-established procedure for the treatment of unicompartmental osteoarthritis and symptomatic varus malalignment. We hypothesized that different fixation devices generate different fixation stability profiles for the various wedge sizes in a finite element (FE) analysis. METHODS Four types of fixation were compared: 1) first and 2) second generation Puddu plates, and 3) TomoFix plate with and 4) without bone graft. Cortical and cancellous bone was modelled and five different opening wedge sizes were studied for each model. Outcome measures included: 1) stresses in bone, 2) relative displacement of the proximal and distal tibial fragments, 3) stresses in the plates, 4) stresses on the upper and lower screw surfaces in the screw channels. RESULTS The highest load for all fixation types occurred in the plate axis. For the vast majority of the wedge sizes and fixation types the shear stress (von Mises stress) was dominating in the bone independent of fixation type. The relative displacements of the tibial fragments were low (in μm range). With an increasing wedge size this displacement tended to increase for both Puddu plates and the TomoFix plate with bone graft. For the TomoFix plate without bone graft a rather opposite trend was observed.For all fixation types the occurring stresses at the screw-bone contact areas pulled at the screws and exceeded the allowable threshold of 1.2 MPa for at least one screw surface. Of the six screw surfaces that were studied, the TomoFix plate with bone graft showed a stress excess of one out of twelve and without bone graft, five out of twelve. With the Puddu plates, an excess stress occurred in the majority of screw surfaces. CONCLUSIONS The different fixation devices generate different fixation stability profiles for different opening wedge sizes. Based on the computational simulations, none of the studied osteosynthesis fixation types warranted an intransigent full weight bearing per se. The highest fixation stability was observed for the TomoFix plates and the lowest for the first generation Puddu plate. These findings were revealed in theoretical models and need to be validated in controlled clinical settings.

The Hydroxyl Side Chain of a Highly Conserved Serine Residue Is Required for Cation Selectivity and Substrate Transport in the Glial Glutamate Transporter GLT-1/SLC1A2

Glutamate transporters maintain synaptic concentration of the excitatory neurotransmitter below neurotoxic levels. Their transport cycle consists of cotransport of glutamate with three sodium ions and one proton, followed by countertransport of potassium. Structural studies proposed that a highly conserved serine located in the binding pocket of the homologous GltPh coordinates l-aspartate as well as the sodium ion Na1. To experimentally validate these findings, we generated and characterized several mutants of the corresponding serine residue, Ser-364, of human glutamate transporter SLC1A2 (solute carrier family 1 member 2), also known as glutamate transporter GLT-1 and excitatory amino acid transporter EAAT2. S364T, S364A, S364C, S364N, and S364D were expressed in HEK cells and Xenopus laevis oocytes to measure radioactive substrate transport and transport currents, respectively. All mutants exhibited similar plasma membrane expression when compared with WT SLC1A2, but substitutions of serine by aspartate or asparagine completely abolished substrate transport. On the other hand, the threonine mutant, which is a more conservative mutation, exhibited similar substrate selectivity, substrate and sodium affinities as WT but a lower selectivity for Na(+) over Li(+). S364A and S364C exhibited drastically reduced affinities for each substrate and enhanced selectivity for l-aspartate over d-aspartate and l-glutamate, and lost their selectivity for Na(+) over Li(+). Furthermore, we extended the analysis of our experimental observations using molecular dynamics simulations. Altogether, our findings confirm a pivotal role of the serine 364, and more precisely its hydroxyl group, in coupling sodium and substrate fluxes.

Erosive tooth wear and wedge-shaped defects in 1996 and 2006: cross- sectional surveys of Swiss army recruits.

The purpose of this study was to determine the prevalence and possible etiological factors of erosive tooth wear and wedge-shaped defects in Swiss Army recruits and compare the findings with those of an analogous study conducted in 1996. In 2006, 621 recruits between 18 and 25 years of age (1996: 417 recruits; ages 19 to 25) were examined for erosive tooth wear and wedge-shaped defects. Additional data was acquired using a questionnaire about personal details, education, dentitions subjective condition, oral hygiene, eating and drinking habits, medications used, and general medical problems. In 2006, 60.1% of those examined exhibited occlusal erosive tooth wear not involving the dentin (1996: 82.0%) and 23.0% involving the dentin (1996: 30.7%). Vestibular erosive tooth wear without dentin involvement was seen in 7.7% in 2006 vs. 14.4% in 1996. Vestibular erosive tooth wear with dentin involvement was rare in both years (0.5%). Oral erosive tooth wear lacking exposed dentin was also rare in those years, although more teeth were affected in 2006 (2.1%) than in 1996 (0.7%). The examinations in 2006 found one or more initial wedge-shaped lesions in 8.5% of the recruits, while 20.4% of the study participants exhibited such in 1996. In 1996, 53% consumed acidic foods and beverages more than 5 times/day; in 2006, 83.9% did so. In neither study did multivariate regression analyses show any significant correlations between occurrence and location of erosive tooth wear and wedge-shaped defects and various other parameters, e.g., eating and hygiene habits, or dentin hyper-sensitivity. Despite a significant increase in consumption of acidic products between 1996 and 2006, the latter study found both fewer erosive tooth wear and fewer wedge-shaped defects (i.e., fewer non-carious lesions.).

Comparisons between analogue and numerical models of thrust wedge development

Analogue and finite element numerical models with frictional and viscous properties are used to model thrust wedge development. Comparison between model types yields valuable information about analogue model evolution, scaling laws and the relative strengths and limitations of the techniques. Both model types show a marked contrast in structural style between ‘frictional-viscous domains’ underlain by a thin viscous layer and purely ‘frictional domains’. Closely spaced thrusts form a narrow and highly asymmetric fold-and-thrust belt in the frictional domain, characterized by in-sequence propagation of forward thrusts. In contrast, the frictional-viscous domain shows a wide and low taper wedge and a thrust belt with a more symmetrical vergence, with both forward and back thrusts. The frictional-viscous domain numerical models show that the viscous layer initially simple shears as deformation propagates along it, while localized deformation resulting in the formation of a pop-up structure occurs in the overlying frictional layers. In both domains, thrust shear zones in the numerical model are generally steeper than the equivalent faults in the analogue model, because the finite element code uses a non-associated plasticity flow law. Nevertheless, the qualitative agreement between analogue and numerical models is encouraging. It shows that the continuum approximation used in numerical models can be used to model frictional materials, such as sand, provided caution is taken to properly scale the experiments, and some of the limitations are taken into account.

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma"

By analogy to gliosarcoma, the term "ependymosarcoma" has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial-sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical - yet not frankly anaplastic - features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to "ependymosarcoma".

The ocular motor features of adult-onset alexander disease: a case and review of the literature

A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle

Neuronal activity within the central nervous system (CNS) strictly depends on homeostasis and therefore does not tolerate uncontrolled entry of blood components. It has been generally believed that under normal conditions, the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB) prevent immune cell entry into the CNS. This view has recently changed when it was realized that activated T cells are able to breach the BBB and the BCSFB to perform immune surveillance of the CNS. Here we propose that the immune privilege of the CNS is established by the specific morphological architecture of its borders resembling that of a medieval castle. The BBB and the BCSFB serve as the outer walls of the castle, which can be breached by activated immune cells serving as messengers for outside dangers. Having crossed the BBB or the BCSFB they reach the castle moat, namely the cerebrospinal fluid (CSF)-drained leptomeningeal and perivascular spaces of the CNS. Next to the CNS parenchyma, the castle moat is bordered by a second wall, the glia limitans, composed of astrocytic foot processes and a parenchymal basement membrane. Inside the castle, that is the CNS parenchyma proper, the royal family of sensitive neurons resides with their servants, the glial cells. Within the CSF-drained castle moat, macrophages serve as guards collecting all the information from within the castle, which they can present to the immune-surveying T cells. If in their communication with the castle moat macrophages, T cells recognize their specific antigen and see that the royal family is in danger, they will become activated and by opening doors in the outer wall of the castle allow the entry of additional immune cells into the castle moat. From there, immune cells may breach the inner castle wall with the aim to defend the castle inhabitants by eliminating the invading enemy. If the immune response by unknown mechanisms turns against self, that is the castle inhabitants, this may allow for continuous entry of immune cells into the castle and lead to the death of the castle inhabitants, and finally members of the royal family, the neurons. This review will summarize the molecular traffic signals known to allow immune cells to breach the outer and inner walls of the CNS castle moat and will highlight the importance of the CSF-drained castle moat in maintaining immune surveillance and in mounting immune responses in the CNS.

Detection of proximal secondary caries at cervical class II-amalgam restoration margins in vitro

To compare the performance of LFpen (DIAGNOdent pen) with two different wedge-shaped tips to conventional bitewing radiography (BW) for detecting proximal secondary caries at the cervical margin of amalgam restorations in vitro.

Giant cell glioblastoma in the cerebrum of a pembroke welsh corgi

A 6-year-old, neutered female Pembroke Welsh corgi was presented with a 1-month history of ataxia and panting. The clinical signs progressed until the dog became anorexic, obtunded and exhibited circling to the left. At necropsy examination, a mass was detected in the left forebrain, impinging on the cribriform plate. Microscopically, the mass was composed of sheets of round to pleomorphic neoplastic cells with vacuolated cytoplasm. Nuclear atypia, anisocytosis and anisokaryosis were common. Numerous bizarre, multinucleated giant cells containing 60 or more nuclei and giant mononuclear cells were present. The matrix contained abundant reticulin. Immunohistochemistry revealed the neoplastic cells uniformly to express vimentin, and a small number of neoplastic cells expressed glial fibrillary acid protein. A diagnosis of giant cell glioblastoma was made. Although well recognized in man, this tumour has been documented rarely in the veterinary literature.

Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, "outrunning" the host's immune response in demyelinating plaques, thus continuously eliciting new lesions.

Sarcomatous evolution of oligodendroglioma ("oligosarcoma"): confirmatory report of an uncommon pattern of malignant progression in oligodendroglial tumors

By analogy to gliosarcoma, the neologism "oligosarcoma" is to describe an uncommon form of biphasic central nervous system tumor composed of contiguous neuroepithelial and mesenchymal elements, each of which individually meet the criteria of oligodendroglioma and sarcoma, respectively. By virtue of its distinctive genotype (codeletion 1p/19q), oligodendroglioma is a particularly inviting paradigm to test the assumption that such mixed tumors are clonally derived from a glial primary. We observed this constellation in a 41-year-old male who underwent two resection procedures for a recurring right frontal tumor at five years' interval. On imaging, both lesions were contrast-enhancing, and measured 7 cm × 7 cm × 6.8 cm and 7 cm × 6.5 cm × 4cm, respectively. Following the first operation, temozolomide monotherapy was administered. Whereas initial histology showed conventional anaplastic oligodendroglioma, the recurrence consisted mostly of a fibrosarcoma-like, fascicular neoplasm that was immunoreactive for vimentin, smooth muscle actin, S100 protein, and focally epithelial membrane antigen. In between, a subset of otherwise indistinguishable spindle cells expressed GFAP, and focally merged with residues of oligodendroglioma. Molecular testing for loss of heterozygosity confirmed codeletion of 1p/19q in both the primary tumor and the sarcomatous recurrence. Similarly, generalized immunoreactivity for the mutant R132H form of isocitrate dehydrogenase in both lesions indicated an identical mutation of the IDH1 gene. By the above standards, biologically consistent "oligosarcomas" are felt to be exceedingly rare, and possibly participate of a nosologically heterogeneous group of combined glial/mesenchymal lesions that may also include iatrogenically induced second malignancies as well as true collision tumors.

Proteomic changes in the rat brain induced by homogenous irradiation and by the bystander effect resulting from high energy synchrotron X-ray microbeams

Abstract Purpose: To further evaluate the use of microbeam irradiation (MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue. Methods: Adult rats were irradiated with 35 or 350 Gy at the European Synchotron Research Facility (ESRF), using homogenous (broad beam) irradiation (HI) or a high energy microbeam delivered to the right brain hemisphere only. The proteome of the frontal lobes were then analyzed using two-dimensional electrophoresis (2-DE) and mass spectrometry. Results: HI resulted in proteomic responses indicative of tumourigenesis; increased albumin, aconitase and triosphosphate isomerase (TPI), and decreased dihydrolipoyldehydrogenase (DLD). The MBI bystander effect proteomic changes were indicative of reactive oxygen species mediated apoptosis; reduced TPI, prohibitin and tubulin and increased glial fibrillary acidic protein (GFAP). These potentially anti-tumourigenic apoptotic proteomic changes are also associated with neurodegeneration. However the bystander effect also increased heat shock protein (HSP) 71 turnover. HSP 71 is known to protect against all of the neurological disorders characterized by the bystander effect proteome changes. Conclusions: These results indicate that the collective interaction of these MBI-induced bystander effect proteins and their mediation by HSP 71, may confer a protective effect which now warrants additional experimental attention.

Proteome and radioimmunoassay analyses of pituitary hormones and proteins in response to feed restriction of dairy cows

The hypothalamic-pituitary system controls homeostasis during feed energy reduction. In order to examine which pituitary proteins and hormone variants are potentially associated with metabolic adaptation, pituitary glands from ad libitum and energy restrictively fed dairy cows were characterized using RIA and 2-DE followed by MALDI-TOF-MS. We found 64 different spots of regulatory hormones: growth hormone (44), preprolactin (16), luteinizing hormone (LH) (1), thyrotropin (1), proopiomelanocortin (1) and its cleavage product lipotropin (1), but none of these did significantly differ between feeding groups. Quantification of total pituitary LH and prolactin concentrations by RIA confirmed the results obtained by proteome analysis. Also, feed energy restriction provoked increasing non-esterified fatty acid, decreasing prolactin, but unaltered glucose, LH and growth hormone plasma concentrations. Energy restriction decreased the expression of glial fibrillary acidic protein, triosephosphate isomerase, purine-rich element-binding protein A and elongation factor Tu, whereas it increased expression of proline synthetase co-transcribed homolog, peroxiredoxin III, beta-tubulin and annexin A5 which is involved in the hormone secretion process. Our results indicate that in response to feed energy restriction the pituitary reservoir of all posttranslationally modified hormone forms remains constant. Changing plasma hormone concentrations are likely attributed to a regulated releasing process from the gland into the blood.

Controversies in the treatment of ingrown nails

Ingrown toenails are one of the most frequent nail disorders of young persons. They may negatively influence daily activities, cause discomfort and pain. Since more than 1000 years, many different treatments have been proposed. Today, conservative and surgical methods are available, which, when carried out with expertise, are able to cure the disease. Packing, taping, gutter treatment, and nail braces are options for relatively mild cases whereas surgery is exclusively done by physicians. Phenolisation of the lateral matrix horn is now the safest, simplest, and most commonly performed method with the lowest recurrence rate. Wedge excisions can no longer be recommended.