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.

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.

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.

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.

Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts.

BACKGROUND: Glioblastoma (GBM) is a tumor of the central nervous system. After surgical removal and standard therapy, recurrence of tumors is observed within 6-9 months because of the high migratory behavior and the infiltrative growth of cells. Here, we investigated whether carnosine (ß-alanine-l-histidine), which has an inhibitory effect on glioblastoma proliferation, may on the opposite promote invasion as proposed by the so-called "go-or-grow concept". METHODS: Cell viability of nine patient derived primary (isocitrate dehydrogenase wildtype; IDH1R132H non mutant) glioblastoma cell cultures and of eleven patient derived fibroblast cultures was determined by measuring ATP in cell lysates and dehydrogenase activity after incubation with 0, 50 or 75 mM carnosine for 48 h. Using the glioblastoma cell line T98G, patient derived glioblastoma cells and fibroblasts, a co-culture model was developed using 12 well plates and cloning rings, placing glioblastoma cells inside and fibroblasts outside the ring. After cultivation in the presence of carnosine, the number of colonies and the size of the tumor cell occupied area were determined. RESULTS: In 48 h single cultures of fibroblasts and tumor cells, 50 and 75 mM carnosine reduced ATP in cell lysates and dehydrogenase activity when compared to the corresponding untreated control cells. Co-culture experiments revealed that after 4 week exposure to carnosine the number of T98G tumor cell colonies within the fibroblast layer and the area occupied by tumor cells was reduced with increasing concentrations of carnosine. Although primary cultured tumor cells did not form colonies in the absence of carnosine, they were eliminated from the co-culture by cell death and did not build colonies under the influence of carnosine, whereas fibroblasts survived and were healthy. CONCLUSIONS: Our results demonstrate that the anti-proliferative effect of carnosine is not accompanied by an induction of cell migration. Instead, the dipeptide is able to prevent colony formation and selectively eliminates tumor cells in a co-culture with fibroblasts.

Proposals for best-quality immunohistochemical staining of paraffin-embedded brain tissue slides in forensics.

Immunohistochemistry (IHC) has become an integral part in forensic histopathology over the last decades. However, the underlying methods for IHC vary greatly depending on the institution, creating a lack of comparability. The aim of this study was to assess the optimal approach for different technical aspects of IHC, in order to improve and standardize this procedure. Therefore, qualitative results from manual and automatic IHC staining of brain samples were compared, as well as potential differences in suitability of common IHC glass slides. Further, possibilities of image digitalization and connected issues were investigated. In our study, automatic staining showed more consistent staining results, compared to manual staining procedures. Digitalization and digital post-processing facilitated direct analysis and analysis for reproducibility considerably. No differences were found for different commercially available microscopic glass slides regarding suitability of IHC brain researches, but a certain rate of tissue loss should be expected during the staining process.

[A phase model of trauma rehabilitation : How can we avoid the "rehab-hole"?] / Phasenmodell der Traumarehabilitation : Wie können wir das "Rehaloch" vermeiden?

Advances in the rescue chain and first aid of polytrauma patients, which have consequently increased their chance of survival, have led to an increase in demands for rehabilitation. However, there is still a large hole in the continuity of rehabilitation between acute patient care and in-patient rehabilitation, the so-called "rehab-hole". The consequences are untapped rehabilitation potential, loss of strength, endurance and motivation as well as impairment of function of the patient.Based on the phase model of neurological/neurosurgical rehabilitation, we propose a step model for the rehabilitation of polytrauma patients that ensures an uninterrupted chain of rehabilitation. After acute patient care (phase a) and a potentially required early patient rehabilitation (phase b), trauma rehabilitation should seamlessly continue on to phase c. The implementation of phase c after acute patient rehabilitation requires changes in the structure of "orthopaedic" rehabilitation clinics and financial support due the large consumption of resources by more complexly injured patients in this phase. The subsequent rehabilitation in phase d is well established and complies with current rehabilitation measures (AHB, BGSW). Further rehabilitation measures may be essential for social and occupational reintegration of the patient (phase e), depending on the complexity of their injuries after the accident. For patients with long-lasting results after an accident, it is crucial to implement continuous follow-ups (phase f) to ensure a better long-term outcome.In order to implement this phase model it is necessary to establish specialized facilities that meet the particular requirements needed for phase c. This tri-phased treatment model in trauma centres can therefore be used in trauma rehabilitation. In addition to the already established local and regional rehabilitation centres, nationwide trauma rehabilitation centres have adopted phase c rehabilitation.

Disseminated oligodendroglial-like leptomeningeal tumors: preliminary diagnostic and therapeutic results for a novel tumor entity [corrected].

Pediatric tumors of the central nervous system composed of oligoid tumor cells showing diffuse leptomeningeal spread without a primary mass lesion seem to represent a novel tumor entity. The terms "diffuse leptomeningeal glioneural tumor" or-preferably-"disseminated oligodendroglial-like leptomeningeal tumor of childhood" (DOGLT) were proposed. Four patients were identified with clinico-neuropathologic findings compatible with DOGLT and a mean follow-up time of 54 months was determined. Seven different biopsies obtained from the four patients were histologically evaluated. Clinical course, diagnostic measures, histopathologic and radiologic features and treatment suggestions were recorded, on the basis of which diagnostic and therapeutic algorithm was proposed. Patients with DOGLT presented with hydrocephalus as first symptom, requiring neurosurgical therapy. Open arachnoid biopsy was necessary to confirm diagnosis. The oligoid cells in a desmoplastic or focally myxoid matrix showed OLIG2-, MAP2-, S-100 and rare HuC/HuD protein-immunopositivity. IDH1 (R132H)- and CD99-immunohistochemistry was negative in all patients. None of the evaluable biopsies of three patients showed chromosome 1p/19q deletion, neither as isolated nor combined allelic loss. Chemotherapy according to the SIOP-LGG 2004 standard induction and consolidation protocol resulted in complete response and partial response, respectively, in 50 % of the patients. However, after discontinuation of chemotherapy, two patients experienced tumor progression and one of them succumbed to the disease after 19 months. Radiological criteria as well as preliminary treatment results are presented after observation of four clinical cases. Prognosis and long-term clinical courses remain to be observed.

On the True Indium Content of In-Filled Skutterudites.

The incongruently melting single-filled skutterudite InxCo4Sb12 is known as a promising bulk thermoelectric material. However, the products of current bulk syntheses contain always impurities of InSb, Sb, CoSb, or CoSb2, which prevent an unbiased determination of its thermoelectric properties. We report a new two-step synthesis of high-purity InxCo4Sb12 with nominal compositions x = 0.12, 0.15, 0.18, and 0.20 that separates the kieftite (CoSb3) formation from the topotactic filler insertion. This approach allows conducting the reactions at lower temperatures with shorter reaction times and circumventing the formation of impurity phases. The synthesis can be extended to other filled skutterudites. High-density (>98%) pellets for thermoelectric characterization were prepared by current-assisted short-time sintering. Sample homogeneity was demonstrated by potential and Seebeck microprobe measurements of the complete pellet surfaces. Synchrotron X-ray diffraction showed a purity of 99.9% product with traces (≤0.1%) of InSb in samples of nominal composition In0.18Co4Sb12 and In0.20Co4Sb12. Rietveld refinements revealed a linear correlation between the true In occupancy and the lattice parameter a. This allows the determination of the true In filling in skutterudites and predicting the In content of unknown AxCo4Sb12. The high purity of InxCo4Sb12 allowed studying the transport properties without bias from side phases. A figure of merit close to unity at 420 °C was obtained for a sample of a true composition of In0.160(2)Co4Sb12 (nominal composition In0.18Co4Sb12). The lower degree of In filling has a dramatic effect on the thermoelectric properties as demonstrated by the sample of nominal composition In0.20Co4Sb12. The presence of InSb in amounts of ∼0.1 vol% led to a substantially lower degree of interstitial site filling of 0.144, and the figure of merit zT decreased by 18%, which demonstrates the significance of the true filler atom content in skutterudite materials.

Amelioration of psychiatric symptoms through exposure to music individually adapted to brain rhythm disorders - a randomised clinical trial on the basis of fundamental research.

INTRODUCTION: This pilot study examined, whether long-term exposure of psychiatric patients to music that was individually adapted to brain rhythm disorders associated with psychoticism could act to ameliorate psychiatric symptoms. METHODS: A total of 50 patients with various psychiatric diagnoses were randomised in a 1:1 ratio to listen to CDs containing either music adapted to brain rhythm anomalies associated with psychoticism - measured via a specific spectral analysis - or standard classical music. Participants were instructed to listen to the CDs over the next 18 months. Psychiatric symptoms in both groups were assessed at baseline and at 4, 8 and 18 months, using the Brief Symptom Inventory (BSI). RESULTS: At 18 months, patients in the experimental group showed significantly decreased BSI scores compared to control patients. Intriguingly, this effect was not only seen for symptoms of psychoticism and paranoia but also for anxiety, phobic anxiety and somatisation. CONCLUSIONS: Exposure to the adapted music was effective in ameliorating psychotic, anxiety and phobic anxiety symptoms. Based on the theories of neuroplasticity and brain rhythms, it can be hypothesised that this intervention may be enhancing brain-rhythm synchronisation and plasticity in prefrontal-hippocampal circuits that are implicated in both psychosis/paranoia and anxiety/phobic anxiety.

Influence of sandblasting and bonding on the shear bond strength between differently pigmented polyetheretherketone (PEEK) and veneering composite after artificial aging.

OBJECTIVE: Achieving a strong bond between Polyetheretherketone (PEEK) and veneering composites is challenging due to PEEKs low surface energy. This study examined the effects of sandblasting and bonding on the shear bond strength (SBS) between veneering composite and pigmented PEEK, considering artificial aging. METHODS: Of three pigmented PEEK compounds (DC4420R, DC4450R, DC4470R; Evonic Operations GmbH, Marl, Germany), 40 specimens each were milled and polished up to 2500 grit. Prior to veneering, specimens were divided into 4 subgroups: Subgroup 1: Polishing; 2: Polishing + bonding; 3: Sandblasting; 4: Sandblasting + bonding. Sandblasting was performed using Al2O3. Adhesive was an agent containing MMA (Signum Universal Bond, Kulzer GmbH, Hanau, Germany). After veneering (Composite, Kulzer GmbH) the subgroups were divided into 2 subgroups. One subgroup was immersed in 37 °C warm distilled water for 24 h. The second subgroup was artificially aged by thermocycling (TCL) with 5000 cycles in distilled water (5 °C / 55 °C; 30 s). Surface roughness, water contact angles and failure modes were recorded. SBS was measured using a universal testing machine. RESULTS: Results demonstrated that the combination of sandblasting and bonding significantly improved the SBS compared to polishing alone. PEEK color did not significantly influence the SBS. Aging by TCL had a negative effect on the SBS. SIGNIFICANCE: Sandblasting and the use of an adhesive containing MMA were found to be effective in achieving satisfactory SBS between veneering composite and pigmented PEEK surfaces. These pretreatment methods demonstrate their potential for establishing durable and reliable bonding in clinical applications.

L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial.

The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation.

PEEK dental implants: a review of the literature.

The insertion of dental implants containing titanium can be associated with various complications (eg, hypersensitivity to titanium). The aim of this article is to evaluate whether there are existing studies reporting on PEEK (polyetheretherketone) as an alternative material for dental implants. A systematic literature search of PubMed until December 2010 yielded 3 articles reporting on dental implants made from PEEK. One article analyzed stress distribution in carbon fiber-reinforced PEEK (CFR-PEEK) dental implants by the 3-dimensional finite element method, demonstrating higher stress peaks due to a reduced stiffness compared to titanium. Two articles reported on investigations in mongrel dogs. The first article compared CFR-PEEK to titanium-coated CFR-PEEK implants, which were inserted into the femurs and evaluated after 4 and 8 weeks. The titanium-coated implants showed significantly higher bone-implant contact (BIC) rates. In a second study, implants of pure PEEK were inserted into the mandibles beside implants made from titanium and zirconia and evaluated after 4 months, where PEEK presented the lowest BIC. The existing articles reporting on PEEK dental implants indicate that PEEK could represent a viable alternative material for dental implants. However, further experimental studies on the chemical modulation of PEEK seem to be necessary, mainly to increase the BIC ratio and to minimize the stress distribution to the peri-implant bone.

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.

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.

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.

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.

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.

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.