CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data.

Homozygous CDKN2A/B deletion has been associated with an increased risk of recurrence in meningiomas. However, the evidence is confined to a limited number of studies, and the importance of heterozygous CDKN2A/B deletions remains insufficiently investigated. Hence, the present meta-analysis reconstructs individual patient data (IPD) and reconstructs the probabilities of progression-free survival (PFS) stratified by CDKN2A/B status. IPD of PFS rates were extracted from published Kaplan-Meier plots using the R package IPDfromKM in R studio (RStudio, Boston, MA, USA). Reconstructed Kaplan-Meier Plots of the pooled IPD data were created. One-stage and two-stage meta-analyses were performed. Hazard ratios (HR) were used as effective measures. Of 181 records screened, four articles with 2521 participants were included. The prevalence of homozygous CDKN2A/B deletions in the included studies was 0.049 (95% CI 0.040-0.057), with higher tumor grades associated with a significantly greater proportion of CDKN2A/B deletions. The reconstructed PFS curves for the pooled cohort showed that the median PFS time of patients with a CDKN2A/B wild-type status, heterozygous or homozygous CDKN2A/B deletion was 180.0 (95% CI 145.7-214.3), 26.1 (95% CI 23.3-29.0), and 11.00 (95% CI 8.6-13.3) months, respectively (p < 0.0001). Both hetero- or homozygous CDKN2A/B deletions were significantly associated with shortened time to meningioma progression. One-stage meta-analysis showed that hetero- (HR: 5.5, 95% CI 4.0-7.6, p < 0.00001) and homozygous CDKN2A/B deletions (HR: 8.4, 95% CI 6.4-11.0, p < 0.00001) are significantly associated with shortened time to meningioma progression. Multivariable Cox regression analysis of progression in a subgroup with available covariates (age, sex, WHO grade, and TERT status) and also two-stage meta-analysis confirmed and validated the results of the one-stage analysis that both heterozygous and homozygous CDKN2A/B deletions are of prognostic importance. Further large-scale studies of WHO grade 2 and 3 meningiomas are needed to validate the importance of heterozygous CDKN2A/B deletions with consideration of established factors.

Tumor size, treatment patterns, and survival in neuro-oncology patients before and during the COVID-19 pandemic.

The COVID-19 pandemic has disrupted healthcare delivery worldwide, leading to significant delays in cancer diagnosis and treatment. This study aimed to investigate the impact of the pandemic on the diagnosis and treatment of malignant brain tumors, specifically glioblastoma (GBM) and cerebral metastasis (CM), in a specialized neuro-oncology center. We analyzed data from 236 patients diagnosed with previously unknown malignant brain tumors between January 2018 and December 2021. Patients were classified into two groups: pre-COVID (January 2018 to December 2019) and COVID (January 2020 to December 2021). Tumor volumes were compared between the two groups and factors affecting tumor volumes were studied. Of 236 patients diagnosed with previously unknown malignant brain tumors, 114 were in the pre-COVID group and 122 were in the COVID group. Median tumor volumes at first diagnosis were significantly larger in the COVID group compared to the pre-COVID group (21.7 vs 15.7 cm3; p < 0.05). The survival times for the overall cohort and the GBM and CM subgroups did not differ significantly between the pre-COVID and COVID periods. Delays in diagnosis and treatment during the COVID-19 pandemic led to larger tumor volumes at diagnosis for patients with malignant brain tumors. However, these larger tumors did not result in worse survival outcomes. This counterintuitive finding highlights the crucial role of specialized neuro-oncological centers in mitigating the potential negative impact of delayed treatment and emphasizes the need for continued access to specialized care during times of crisis.

Ultrasonic welding of polyetheretherketone for dental applications.

OBJECTIVE: Due to its favorable properties, the high-performance polymer polyetheretherketone (PEEK) is used as a metal-free alternative for the fabrication of denture frameworks. For dental applications, PEEK is available in different colors, such as red or white, by compounding with different fillers. In order to permanently bond such different dental PEEK types together in a denture framework, ultrasonic welding could be a viable process. Therefore, the aim of this study was to determine the optimum processing welding parameters for welding different dental PEEK grades in terms of maximum weld strength. METHODS: Rectangular plates from three PEEK compounds were prepared according to the dimensions of a removable partial denture (RPD) of PEEK. These were combined in a way that four groups resulted, whereas the combination of pure PEEK served as control. In each group, 5 samples were ultrasonically welded at one of four welding energies using a microprocessor-controlled ultrasonic welder, where the welder was activated only once. Afterwards, the samples were subjected to tensile tests to evaluate the shear bond strength (SBS) of the joint. RESULTS: Increasing the welding energy resulted in an increase in the welding time. Accordingly, the increase in the welding energy increased the surface deformation for all tested samples. The shear bond strengths ranged from 4.8 ± 0.68 MPa for samples welded with 50 Ws to 16.37 ± 1.69 MPa for samples welded with 90 Ws. Excessive weld energy of 130 Ws led to a significant decrease of SBS due to a severe indentation and perforation induced by the sonotrode. SIGNIFICANCE: The SBS and topography of the welded samples were systematically studied and the optimal welding parameters were determined. This could serve as a reference and instruction for clinical applications.

Droplet Degeneration of Hippocampal and Cortical Neurons Signifies the Beginning of Neuritic Plaque Formation.

BACKGROUND: Neuritic plaques contain neural and microglial elements, and amyloid-ß protein (Aß), but their pathogenesis remains unknown. OBJECTIVE: Elucidate neuritic plaque pathogenesis. METHODS: Histochemical visualization of hyperphosphorylated-tau positive (p-tau+) structures, microglia, Aß, and iron. RESULTS: Disintegration of large projection neurons in human hippocampus and neocortex presents as droplet degeneration: pretangle neurons break up into spheres of numerous p-tau+ droplets of various sizes, which marks the beginning of neuritic plaques. These droplet spheres develop in the absence of colocalized Aß deposits but once formed become encased in diffuse Aß with great specificity. In contrast, neurofibrillary tangles often do not colocalize with Aß. Double-labelling for p-tau and microglia showed a lack of microglial activation or phagocytosis of p-tau+ degeneration droplets but revealed massive upregulation of ferritin in microglia suggesting presence of high levels of free iron. Perl's Prussian blue produced positive staining of microglia, droplet spheres, and Aß plaque cores supporting the suggestion that droplet degeneration of pretangle neurons in the hippocampus and cortex represents ferroptosis, which is accompanied by the release of neuronal iron extracellularly. CONCLUSION: Age-related iron accumulation and ferroptosis in the CNS likely trigger at least two endogenous mechanisms of neuroprotective iron sequestration and chelation, microglial ferritin expression and Aß deposition, respectively, both contributing to the formation of neuritic plaques. Since neurofibrillary tangles and Aß deposits colocalize infrequently, tangle formation likely does not involve release of neuronal iron extracellularly. In human brain, targeted deposition of Aß occurs specifically in response to ongoing ferroptotic droplet degeneration thereby producing neuritic plaques.

Mechanical Properties of New Generations of Monolithic, Multi-Layered Zirconia.

New monolithic multi-layered zirconia restorations are gaining popularity due to their excellent aesthetic properties. However, current knowledge of these newest multi-layer ceramics in terms of mechanical properties is scarce. Three monolithic, multi-layered zirconia materials (Katana, Kuraray Noritake, Japan) were selected for comparison: High Translucent Multi-layered zirconia (HTML), Super Translucent Multi-layered zirconia (STML) and Ultra Translucent Multi-layered zirconia (UTML). Fifteen specimens per group were cut from pre-sintered blocs in each of the four layers (L1, L2, L3, L4) and in different thicknesses (0.4 mm, 0.8 mm and 1.2 mm). Critical fracture load (Fcf) was recorded in 3-point-bending. Flexural strength (σ) in MPa, Vickers hardness (HV) in N/mm2, fracture toughness (KIc) in MPa*m1/2, Weibull Modulus (m) and characteristic Weibull strength (σw) in MPa were assessed. Statistical analysis was performed using ANOVA analysis. FS and KIc were significantly higher (p < 0.05) for Katana™ HTML (652.85 ± 143.76−887.64 ± 118.95/4.25 ± 0.43−5.01 ± 0.81) in comparison to Katana™ STML (280.17 ± 83.41−435.95 ± 73.58/3.06 ± 0.27−3.84 ± 0.47) and UTML (258.25 ± 109.98−331.26 ± 56.86/2.35 ± 0.31−2.94 ± 0.33), with no significant differences between layers and layer thicknesses. The range of indications should be carefully considered when selecting the type of monolithic zirconia for fabrication of dental restorations, as materials widely differ in mechanical properties.

Whole tissue and single cell mechanics are correlated in human brain tumors.

Biomechanical changes are critical for cancer progression. However, the relationship between the rheology of single cells measured ex-vivo and the living tumor is not yet understood. Here, we combined single-cell rheology of cells isolated from primary tumors with in vivo bulk tumor rheology in patients with brain tumors. Eight brain tumors (3 glioblastoma, 3 meningioma, 1 astrocytoma, 1 metastasis) were investigated in vivo by magnetic resonance elastography (MRE), and after surgery by the optical stretcher (OS). MRE was performed in a 3-Tesla clinical MRI scanner and magnitude modulus |G*|, loss angle φ, storage modulus G', and loss modulus G'' were derived. OS experiments measured cellular creep deformation in response to laser-induced step stresses. We used a Kelvin-Voigt model to deduce two parameters related to cellular stiffness (µKV) and cellular viscosity (ηKV) from OS measurements in a time regimen that overlaps with that of MRE. We found that single-cell µKV was correlated with |G*| (R = 0.962, p < 0.001) and G'' (R = 0.883, p = 0.004) but not G' of the bulk tissue. These results suggest that single-cell stiffness affects tissue viscosity in brain tumors. The observation that viscosity parameters of individual cells and bulk tissue were not correlated suggests that collective mechanical interactions (i.e. emergent effects or cellular unjamming) of many cancer cells, which depend on cellular stiffness, influence the mechanical dissipation behavior of the bulk tissue. Our results are important to understand the emergent rheology of active multiscale compound materials such as brain tumors and its role in disease progression.

[Requirements for trauma rehabilitation centers : Post-acute rehabilitation (phase C) after severe trauma injury]. / Anforderungen an Traumarehabilitationszentren : Postakute Rehabilitation (Phase C) nach schwerer Unfallverletzung.

Severely injured patients need a qualified and seamless rehabilitation after the end of the acute treatment. This post-acute rehabilitation (phase C) places high demands on the rehabilitation facility in terms of personnel, material, organizational and spatial requirements.The working group on trauma rehabilitation of the German Society for Orthopedics and Traumatology e. V. (DGOU) and other experts have agreed on requirements for post-acute phase C rehabilitation for seriously injured people. These concern both the personnel and material requirements for a highly specialized orthopedic trauma surgery trauma rehabilitation as well as the demands on processes, organization and quality assurance.A seamless transition to the follow-up and further treatment of seriously injured people in the TraumaNetzwerk DGU® is ensured through a high level of qualification and the corresponding infrastructure of supraregional trauma rehabilitation centers. This also places new demands on the TraumaZentren DGU®. Only if these are met can the treatment and rehabilitation of seriously injured people be optimized.

Performance of PEEK based telescopic crowns, a comparative study.

OBJECTIVE: Telescopic crowns are suitable components of partial dentures to efficiently anchor dental supra-structures to teeth or dental implants and achieve high chewing performance and wear comfort. Usually alloy- or metal-based structures are used for the primary and the secondary crowns. The advantage is the possibility to produce precise structures with a high perfection and sufficient friction force, but the disadvantage is the corrosion instability. The recent introduction of zirconia ceramics has enabled the fabrication of ceramic primary crowns, thus reducing corrodibility. The novel application of the high-performance polymer polyetheretherketone (PEEK) as another metal-free alternative material offers a new perspective for such applications. Therefore, the aim of this work was to assess the performance of telescopic crowns of PEEK by comparing telescopic crowns based on the combination of PEEK (prim. crown) + PEEK (sec. crown) with the pairings ZrO2 (prim. crown) + PEEK (sec. crown) and CoCr-alloy (prim. crown) + PEEK (sec. crown). METHODS: All specimens were CAD/CAM planned and manufactured based on a model of a tooth 26. One master dental technician performed the post-treatment. For each group of material pairing, n = 9 telescopic crown pairs were manufactured and tested. Herein not only the maximum retention force was measured but also the retention force vs. pull-off distance were analyzed. As there is no commonly accepted test protocol available, the influence of various pull off speeds were tested as well. All measurements were first made with three blocks of three crowns (3C), subsequently with three blocks of two crowns (2C) and finally with nine single crowns (1C). The long-term behavior was estimated by performing 10.000 cycles, which is related to a life-time of more than 10 years. RESULTS: The maximum retention force in case of PEEK + PEEK was higher in comparison to the other tested material pairings. In the range between 1 and 10 mm/ min pull off speed there was no significant influence by the pull off speed. More influence on the friction force would be expected by changes of the number of the crowns acting simultaneously. The friction force was decreasing with decreasing number of crowns but not linearly in any tested case. The long-term test has shown that the friction force remained constant. SIGNIFICANCE: The performance of PEEK + PEEK telescopes is comparable with the usually applied material pairings. Over long time no loss in retention force could be observed. The retention force - distance progression in the PEEK + PEEK pairing offers more security against a possible loss of retention during repair or relining. For further tests of the performance of telescopic crowns or to estimate of friction force limits, a setup with at least two, but preferably three, crowns tested in parallel is suggested.

A New Setup for Simulating the Corrosion Behavior of Orthodontic Wires.

The aim of this study was to create a new reliable setup to evaluate commercially available orthodontic wires used during orthodontic treatment. The setup includes various techniques applied for testing metal alloy materials. The materials were tested under extreme conditions to simulate their behavior in the mouth. The alloy composition of each wire was tested. The electrochemical (EC) testing and characterization of the corrosion performance of the wires was calculated by the electrochemical curves at pH = 1 in two different applied potentials to test the reaction of the material. The liquid collected after the EC measurements was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) to verify the reliability of the EC curves and for a more accurate evaluation of the corrosion behavior of the wires. Therefore, the EC measurements were compared to the actual values obtained from the released ions found in the solution. At the end, a surface analysis was performed to detect corrosion on the wires. In conclusion, this study developed a setup to test and better understand the corrosion behavior and ion release of the orthodontic wires, metal alloy dental materials, and other metals used in the oral cavity. This method can contribute to dental material selection in patients with underlying health conditions.

The Video Microscopy-Linked Electrochemical Cell: An Innovative Method to Improve Electrochemical Investigations of Biodegradable Metals.

An innovative, miniature video-optical-electrochemical cell was developed and tested that allows for the conducting of electrochemical corrosion measurements and simultaneous microscopic observations over a small, well-defined surface area of corroding or degrading samples. The setup consisted of a miniature electrochemical cell that was clamped onto the metal sample and fixed under a video microscope before being filled with electrolyte. The miniature cell was comprised of afferent/efferent electrolyte ducts as well as a connection to the Mini Cell System (MCS) for electrochemical measurements. Consequently, all measured and induced currents and voltages referred to the same small area corroding completely within the field of view of the microscope, thus allowing for real-time observation and linking of surface phenomena such as hydrogen evolution and oxide deposition to electrochemical data. The experimental setup was tested on commercial purity (cp) and extra-high purity (XHP) magnesium (Mg) samples using open circuit potential and cyclic voltammetry methods under static and flowing conditions. The corrosion potential was shifted more anodically for cp Mg in comparison to XHP Mg under dynamic conditions. The corrosion current assessed from the cyclic voltametric curves were higher for the cp Mg in comparison to XHP Mg. However, there were no differences between static and flow conditions in the case of XHP Mg in contrast to cp Mg, where the current density was two times higher at dynamic conditions. The measurements and observations with this new method pave the way for a more detailed understanding of magnesium corrosion mechanisms, thus improving predictive power of electrochemical corrosion measurements on newly developed magnesium or other biodegradable alloys applied for medical devices. Different electrochemical tests can be run under various conditions, while being easy to set up and reproduce as well as being minimally destructive to the sample.

Standardized Magnetic Resonance Imaging Reporting Using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation Criteria and Magnetic Resonance Imaging/Transrectal Ultrasound Fusion with Transperineal Saturation Biopsy to Select Men on Active Surveillance.

BACKGROUND: Contemporary selection criteria for men with prostate cancer (PC) suitable for active surveillance (AS) are unsatisfactory, leading to high disqualification rates based on tumor misclassification. Conventional biopsy protocols are based on standard 12-core transrectal ultrasound (TRUS) biopsy. OBJECTIVE: To assess the value of magnetic resonance imaging (MRI)/TRUS fusion biopsy over 4-yr follow-up in men on AS for low-risk PC. DESIGN, SETTING, AND PARTICIPANTS: Between 2010 and 2018, a total of 273 men were included. Of them, 157 men with initial 12-core TRUS biopsy and 116 with initial MRI/TRUS fusion biopsy were followed by systematic and targeted transperineal MRI/TRUS fusion biopsies based on Prostate Cancer Research International Active Surveillance criteria. MRI from follow-up MRI/TRUS fusion biopsy was assessed using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: AS-disqualification rates for patients on AS initially diagnosed by either 12-core TRUS biopsy or by MRI/TRUS fusion biopsy were compared using Kaplan-Meier estimates, log-rank tests, and regression analyses. We also analyzed the influence of negative primary MRI and PRECISE scoring to predict AS disqualification using Kaplan-Meier estimates, log-rank tests, and receiver operating characteristic (ROC) curve analysis. RESULTS AND LIMITATIONS: Of men diagnosed by 12-core TRUS biopsy, 59% were disqualified from AS based on the results of subsequent MRI/TRUS fusion biopsy. In the initial MRI fusion biopsy cohort, upgrading occurred significantly less frequently (19%, p<0.001). ROC curve analyses demonstrated good discrimination for the PRECISE score with an area under the curve of 0.83. No men with a PRECISE score of 1 or 2 (demonstrating absence or downgrading of lesions in follow-up MRI) were disqualified from AS. In our cohort, a negative baseline MRI scan was not a predictor of nondisqualification from AS. Limitations include transperineal approach and extended systematic biopsies used with MRI/TRUS fusion biopsy, which may not be representative of other centers. CONCLUSIONS: MRI/TRUS fusion biopsies allow a reliable risk classification for patients who are candidates for AS. The application of the PRECISE scoring system demonstrated good discrimination. PATIENT SUMMARY: In this study, we investigated the value of multiparametric magnetic resonance imaging (MRI) and MRI/transrectal ultrasound (TRUS) fusion biopsies for the assessment of active surveillance (AS) reliability using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation criteria. Standard TRUS biopsies lead to significant underestimation of prostate cancer. In contrast, MRI/TRUS fusion biopsies allowed for a more reliable risk classification. For appropriate inclusion into AS, men should receive either an initial or a confirmatory MRI/TRUS fusion biopsy.

The impact of different low-pressure plasma types on the physical, chemical and biological surface properties of PEEK.

OBJECTIVE: Plasma treatment can be used as surface treatment of PEEK (poly-ether-ether-ketone) to increase the bonding strength between veneering composite and dental prosthetic frameworks of PEEK or enhance biocompatibility of PEEK implants. These improvements are probably based on chemical changes of the PEEK surface. However, the aim of the study was to evaluate the impact of different low-pressure plasma treatments on surface properties of PEEK, such as roughness, hydrophilicity, micro-hardness, crystallinity and biological activity of PEEK. METHODS: Due to different plasma treatments, 143 disc-shaped specimens of pure implantable PEEK were divided into 4 groups: PEEK (no plasma treatment, n = 29), H-PEEK (hydrogen plasma treatment, n = 38), O-PEEK (oxygen plasma treatment, n = 38), H/O-PEEK (hydrogen/oxygen plasma treatment with a gas mix ratio of 2:1, n = 38). Subsequently, surface roughness, surface contact angle, surface crystallinity, surface micro-hardness and human osteoblast cell coverage area of each group were examined. RESULTS: The hydrophilicity, crystallinity and micro-hardness of the plasma-treated groups increased significantly compared to the untreated group, whereas significant differences in the results of the micro-hardness tests could be shown between all groups up to a test force of 0.02N. Cell density was significantly higher on treated vs. untreated PEEK surfaces. Oxygen and H/O plasma treatments revealed to be most effective, whereas H/O plasma worked ten times faster to achieve the same effects. SIGNIFICANCE: The hydrogen-oxygen, 2/1-mixed plasma treatment combines the effect of hydrogen and oxygen plasma which strongly improve the surface properties of PEEK implant material, such as hydrophilicity, crystallinity, surface micro-hardness and HOB cell adhesion.

Mechanical properties of fused filament fabricated PEEK for biomedical applications depending on additive manufacturing parameters.

DESIGN: of experiments was employed to investigate the combinations of 3D-printing parameters for Polyether ether ketone (PEEK) with a fused filament fabrication (FFF) process and to quantitatively evaluate the quality of 3D printed parts. This research was conducted using a newly developed FFF 3D printer and PEEK filament. Standard PEEK parts were 3D printed for bending and compression tests. Based on the Box-Behnken design, a three factors based experiment was designed using the Response Surface Methodology (RSM). Nozzle diameter, nozzle temperature and printing speed were involved. The density and dimensional accuracy of these printed parts were evaluated, and the bending and compression tests were conducted. The nozzle diameter was found to be the most significant parameter affecting the bending and compression performance of the printed PEEK samples, followed by printing speed and nozzle temperature. The highest accuracy in sample width was obtained with a 0.6 mm nozzle while the most accurate diameter was obtained with a 0.4 mm nozzle. A combination of a 0.4 mm nozzle diameter, 430 °C nozzle temperature and printing speed of 5 mm/s was beneficial to get the densest samples and therefore the highest bending strength; a reduction of internal defects was achieved with a 0.2 mm nozzle, a higher nozzle temperature of 440 °C and slower printing speed leading to better bending modulus. The best compression properties were achieved with a 0.6 mm nozzle, with relatively low influence of the other parameters. Different parameter combinations have been found to obtain optimal mechanical properties. Optimized parameters for better dimension accuracy of small additively manufactured PEEK parts were also achieved depending on the shape of the specimens.

Tumor-to-Tumor Metastasis of Multiple Meningiomas and Clear Cell Renal Cell Carcinoma Metastasis as First Clinical Appearance of Kidney Cancer: A Case Report and Analysis.

Background Meningioma accounts for more than 35% of all diagnosed brain tumors of the central nervous system and, moreover, it is the most common benign recipient of tumor-to-tumor metastasis. Several cases with tumor-to-meningioma metastasis by breast, lung, and intestinal cancer have been described before. Case description The case of a patient with a longstanding history of multiple meningiomas ( n = 4) that suddenly became symptomatic and progressive in size is presented. Following extirpation of the two largest meningiomas, a histological examination revealed two separate tumor-to-meningioma metastases of clear cell renal cell carcinoma that was undiagnosed before. Post-surgical computed tomography scan then confirmed tumor-suspect lesions in both kidneys. After recovery and rehabilitation, adjuvant radio-chemo-therapy was applied according to protocols for kidney cancer. No other tumor-to-tumor-suspect event occurred since then for the remaining two meningiomas. Conclusion Review of literature and our case strengthens the idea of meningioma as a favorable premetastatic niche. Considering that the patient lived with a stable disease for many years, a sudden progress of tumor size in association with neurological deterioration was highly suspected for malign involvement, including the possibility of tumor-to-tumor metastasis. Physicians should be aware about this phenomenon and treat patients accordingly to the underlying disease.

Parameters Influencing the Outcome of Additive Manufacturing of Tiny Medical Devices Based on PEEK.

In this review, we discuss the parameters of fused deposition modeling (FDM) technology used in finished parts made from polyether ether ketone (PEEK) and also the possibility of printing small PEEK parts. The published articles reporting on 3D printed PEEK implants were obtained using PubMed and search engines such as Google Scholar including references cited therein. The results indicate that although many have been experiments conducted on PEEK 3D printing, the consensus on a suitable printing parameter combination has not been reached and optimized parameters for printing worth pursuing. The printing of reproducible tiny-sized PEEK parts with high accuracy has proved to be possible in our experiments. Understanding the relationships among material properties, design parameters, and the ultimate performance of finished objects will be the basis for further improvement of the quality of 3D printed medical devices based on PEEK and to expand the polymers applications.

High-translucent yttria-stabilized zirconia ceramics are wear-resistant and antagonist-friendly.

OBJECTIVES: To evaluate two-body wear of three zirconia ceramics stabilized with 3, 4 and 5mol% yttria and to compare their wear behavior with that of a lithium-disilicate glass-ceramic. METHODS: Sixteen rectangular-shaped specimens made from three grades of zirconia ceramics and a lithium-disilicate glass-ceramic were polished and dynamically loaded in a chewing simulator (2kg vertical load, 2.1Hz) under water at 90°C for 1.2×106 cycles (about 7 days) in the ball-on-plate mode against steatite antagonists. Surface roughness was measured before and after wear testing. Wear tracks were scanned with a non-contact 3D profilometer and super-impositions were used to determine wear loss of the antagonists. Wear surfaces were imaged by SEM. XRD and micro-Raman spectroscopy were used to characterize phase transformation and stress status in the worn and unworn areas of the zirconia ceramics. RESULTS: Independent of fracture toughness, strength and aging-susceptibility, the three zirconia ceramics showed a similar and limited amount of wear (∼10µm in depth) and were more wear-resistant than the lithium-disilicate glass-ceramic (∼880µm in depth). Abrasive wear without obvious cracks was observed for all investigated zirconias, whereas the glass-ceramic with a lower fatigue threshold and high susceptibility to surface dissolution exhibited significant abrasion, fatigue and corrosion wear. All three zirconia ceramics yielded a lower antagonist wear than the glass-ceramic and no significant differences were found between the zirconia ceramics. SIGNIFICANCE: In the context of this study, high-translucent zirconia ceramics stabilized with a higher yttria content, recently introduced in the dental field, were as wear-resistant and antagonist-friendly as conventional high-strength zirconia and suitable for monolithic restorations.

Survival-time dependent increase in neuronal IL-6 and astroglial GFAP expression in fatally injured human brain tissue.

Knowledge on trauma survival time prior to death following a lethal traumatic brain injury (TBI) may be essential for legal purposes. Immunohistochemistry studies might allow to narrow down this survival interval. The biomarkers interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP) are well known in the clinical setting for their usability in TBI prediction. Here, both proteins were chosen in forensics to determine whether neuronal or glial expression in various brain regions may be associated with the cause of death and the survival time prior to death following TBI. IL-6 positive neurons, glial cells and GFAP positive astrocytes all concordantly increase with longer trauma survival time, with statistically significant changes being evident from three days post-TBI (p < 0.05) in the pericontusional zone, irrespective of its definite cortical localization. IL-6 staining in neurons increases significantly in the cerebellum after trauma, whereas increasing GFAP positivity is also detected in the cortex contralateral to the focal lesion. These systematic chronological changes in biomarkers of pericontusional neurons and glial cells allow for an estimation of trauma survival time. Higher numbers of IL-6 and GFAP-stained cells above threshold values in the pericontusional zone substantiate the existence of fatal traumatic changes in the brain with reasonable certainty.

Assessment of ApoC1, LuzP6, C12orf75 and OCC-1 in cystic glioblastoma using MALDI-TOF mass spectrometry, immunohistochemistry and qRT-PCR.

Mass spectrometric analysis of glioblastoma cyst fluids has disclosed a protein peak with m/z 6424-6433. Among the proteins, potentially generating this peak are ApoC1 and LuzP6. To further elucidate protein expression of glioblastoma cells, we analyzed MALDI-TOF results of cyst fluid, performed immunohistochemistry and mRNA analysis. MALDI-TOF protein extraction from 24 glioblastoma cyst fluids was performed with a weak cation exchange. 50 glioblastoma samples were stained with two custom-made antibodies against LuzP6 and commercial antibodies against ApoC1, C12orf75 and OCC-1 and analyzed. For mRNA detection, 16 tissue samples were stored in RNAlater, extracted using the miRNeasy kit and reversely transcribed. For 12 patients, synopsis of results from all three examinations was possible. MALDI-TOF confirmed the peak at 6433 Da in 75% of samples. Immunohistochemically, LuzP6 was detected in 92% (LuzP61-29) and 96% (LuzP630-58) of samples and ApoC1 in 66%. Mean mRNA levels were highest for ApoC1, followed by LuzP6. No correlation between mRNA expression, immunohistochemical staining and intensity of the MALDI-TOF peaks was found. An unequivocal identification of one protein as the source for the 6433 peak is not possible, but our results point to ApoC1 and LuzP6 as the underlying proteins.

Bacterial leakage and bending moments of screw-retained, composite-veneered PEEK implant crowns.

Due to its elastic modulus close to bone, the high-performance material PEEK (polyetheretherketone) represents an interesting material for implant-supported dental prostheses. Besides a damping effect of masticatory forces, it might have a sealing effect against bacterial leakage of the implant-abutment interface (IAI). So far, PEEK has only been used for provisional implant crowns. Therefore, the aim of the study was the evaluation of the bacterial tightness of screw-retained PEEK crowns on titanium implants with conical IAI during masticatory simulation and subsequent bending moment testing. Ten screw-retained implant crowns in the shape of an upper central incisor consisting of a PEEK crown framework veneered with composite were connected to NobelActive RP titanium implants (4.3 × 11.5 mm, Nobel Biocare AB, Göteborg, Sweden) with a tightening torque of 15 Ncm. Prior to tightening, the interior of the implant was inoculated with a bacterial suspension of Enterococcus faecium. The specimens were overmolded with indicating agar (Kanamycin-Aesculin-Azid-Agar (KAAA), Oxoid Limited, Basingstoke United Kingdom), that turns black in contact with E. faecium. The specimens were subjected to a cyclic masticatory simulation whereby a force of 50 N cm was applied at an angle of 30° to the implant axis for 1.2 million cycles. Afterwards, the specimens were subjected to a static loading test according to ISO 14801:2007 to determine the bending moment. During masticatory simulation neither a loosening of the implant screws nor any damage to the veneer or the PEEK framework occurred. Furthermore, no bacterial leakage could be observed in any of the specimens. The average maximum bending moment was measured at 352.13 ±â€¯48.96 N cm. Regarding masticatory forces, PEEK implant crowns seem to be applicable as definitive implant-supported restorations. Furthermore, the bacterial tightness of the IAI of screw-retained one-piece PEEK implant crowns is advantageous compared to superstructures of conventional materials. Further studies are necessary to substantiate the clinical significance of these findings.

Microglial activation occurs late during preclinical Alzheimer's disease.

Sporadic Alzheimer's disease (AD) is marked by a lengthy preclinical phase during which patients are nonsymptomatic but show pathology in variable manifestations. Whether or not neuroinflammation occurs in such nondemented individuals is unknown. We evaluated the medial temporal lobe of 66 nondemented subjects, aged 42-93, in terms of tau pathology, Aß deposition, and microglial activation. We show that 100% of subjects had neurofibrillary degeneration (NFD), 35% had Aß deposits, and 8% revealed microglial activation in individuals where early amyloid formation was apparent by Congo Red staining. Amyloid-induced neuroinflammatory clusters of Iba1, CD68, and ferritin-positive microglia were evident in the immediate vicinity of aggregated Aß. Microglia in the adjacent neuropil were nonactivated. Thus, neuroinflammation in AD represents a highly localized phagocyte reaction, essentially a foreign body response, geared toward removal of insoluble Aß. Because clustered microglia in some amyloid plaques were dystrophic and ferritin-positive, we hypothesize that these cells were exhausted by their attempts to remove the aggregated, insoluble Aß. Our findings show that the sequence of pathologic events in AD begins with tau pathology, followed by Aß deposition, and then by microglial activation. Because only 8% of our subjects revealed all three hallmark pathologic features, we propose that these nondemented individuals were near the threshold of transitioning from nonsymptomatic to symptomatic disease. The onset of neuroinflammation in AD may thus represent a tipping point in AD pathogenesis. Our study suggests that the role of microglia in AD pathogenesis entails primarily the attempted removal of potentially toxic, extracellular material.