Chronic Pharmacological mGluR5 Inhibition Prevents Cognitive Impairment and Reduces Pathogenesis in an Alzheimer Disease Mouse Model.

Beta-amyloid (Aβ) oligomers contribute to the pathophysiology of Alzheimer disease (AD), and metabotropic glutamate receptor 5 (mGluR5) has been shown to act as a receptor for both Aβ oligomers and cellular prion proteins. Furthermore, the genetic deletion of mGluR5 in an APPswe/PS1ΔE9 mouse model of AD improves cognitive function and reduces Aβ plaques and Aβ oligomer concentrations. Here, we show that chronic administration of the orally bioavailable mGluR5-selective negative allosteric modulator CTEP, which is similar in structure, potency, and selectivity to Basimglurant (RO4917523), which is currently in phase II clinical development for major depressive disorder and fragile X syndrome, reverses cognitive decline in APPswe/PS1ΔE9 mice and reduces Aβ plaque deposition and soluble Aβ oligomer concentrations in both APPswe/PS1ΔE9 and 3xTg-AD male mice.

Direct electrospinning of 3D auricle-shaped scaffolds for tissue engineering applications.

Thirty-two poly(ε)caprolactone (PCL) scaffolds have been produced by electrospinning directly into an auricle-shaped mould and seeded with articular chondrocytes harvested from bovine ankle joints. After seeding, the auricle shaped constructs were cultured in vitro and analysed at days 1, 7, 14 and 21 for regional differences in total DNA, glycosaminoglycan (GAG) and collagen (COL) content as well as the expression of aggrecan (AGG), collagen type I and type II (COL1/2) and matrix metalloproteinase 3 and 13 (MMP3/13). Stress-relaxation indentation testing was performed to investigate regional mechanical properties of the electrospun constructs.

Interactive graph-cut segmentation for fast creation of finite element models from clinical ct data for hip fracture prediction.

In this study, we propose interactive graph cut image segmentation for fast creation of femur finite element (FE) models from clinical computed tomography scans for hip fracture prediction. Using a sample of N = 48 bone scans representing normal, osteopenic and osteoporotic subjects, the proximal femur was segmented using manual (gold standard) and graph cut segmentation. Segmentations were subsequently used to generate FE models to calculate overall stiffness and peak force in a sideways fall simulations.

Ceramic cement as a potential stand-alone treatment for bone fractures: An in vitro study of ceramic-bone composites.

Background: A vertebral burst fracture (VBF) treated with vertebroplasty using a ceramic cement consists of four regions; native bone fragments, native ceramic cement, ceramic cement-trabecular bone (ceramic-bone) composite and ceramic-bone interface. Although the mechanical properties of native bone and native ceramic cements have been well investigated, the mechanical properties of ceramic-bone composite and ceramic-bone interface remain unknown. Therefore, the aim of this study was to determine the mechanical properties of ceramic-bone composites and ceramic-bone interfaces.

The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress.

Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress.

The Effectiveness of Percutaneous Vertebroplasty Is Determined by the Patient-Specific Bone Condition and the Treatment Strategy.

Purpose: Vertebral fragility fractures are often treated by injecting bone cement into the collapsed vertebral bodies (vertebroplasty). The mechanisms by which vertebroplasty induces pain relief are not completely understood yet and recent debates cast doubt over the outcome of the procedure. The controversy is intensified by inconsistent results of randomized clinical trials and biomechanical studies that have investigated the effectiveness or the change in biomechanical response due to the reinforcement.

In silico investigation of vertebroplasty as a stand-alone treatment for vertebral burst fractures.

Background: The use of percutaneous vertebroplasty as a stand-alone treatment for stable vertebral burst fractures has been investigated in vitro and in clinical studies. These studies present inconsistent results on the mechanical response of vertebroplasty-treated burst fractures. In addition, observations of the loss of sagittal alignment after vertebroplasty raise questions on the applicability of vertebroplasty for burst fractures.

Tip-enhanced Raman spectroscopy: plasmid-free vs. plasmid-embedded DNA.

Tip-enhanced Raman spectroscopy (TERS) provides greatly enhanced Raman signals along with ultra-high lateral spatial resolutions and has been demonstrated to be a technique of choice to study a variety of biochemical specimens such as DNA and RNA at the single chain level. However, the sensitivity of TERS to demonstrate the influence of the nanoscale environment on DNA properties has not been investigated. Herein, we used a gap-mode TERS as an ultra-sensitive label-free technique to investigate the influence of the local plasmid on the DNA properties of a β2-adrenergic receptor (β2AR).

Patch-augmented rotator cuff repair: influence of the patch fixation technique on primary biomechanical stability.

Introduction: There is an ongoing debate about the potential of patch augmentation to improve biomechanical stability and healing associated with rotator cuff repair. The biomechanical properties of three different patch-augmented rotator cuff repair techniques were assessed in vitro and compared with a standard repair. Dermal collagen patch augmentation may increase the primary stability and strength of the repaired tendon in vitro, depending on the technique used for patch application.

Screw insertion in trabecular bone causes peri-implant bone damage.

Secure fracture fixation is still a major challenge in orthopedic surgery, especially in osteoporotic bone. While numerous studies have investigated the effect of implant loading on the peri-implant bone after screw insertion, less focus has been put on bone damage that may occur due to the screw insertion process itself. Therefore, the aim of this study was to localize and quantify peri-implant bone damage caused by screw insertion.

PSD-95 regulates CRFR1 localization, trafficking and β-arrestin2 recruitment.

Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic-pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses.

Correction tool for Active Shape Model based lumbar muscle segmentation.

In the clinical environment, accuracy and speed of the image segmentation process plays a key role in the analysis of pathological regions. Despite advances in anatomic image segmentation, time-effective correction tools are commonly needed to improve segmentation results. Therefore, these tools must provide faster corrections with a low number of interactions, and a user-independent solution.

Controlled positioning of analytes and cells on a plasmonic platform for glycan sensing using surface enhanced Raman spectroscopy.

The rise of molecular plasmonics and its application to ultrasensitive spectroscopic measurements has been enabled by the rational design and fabrication of a variety of metallic nanostructures. Advanced nano and microfabrication methods are key to the development of such structures, allowing one to tailor optical fields at the sub-wavelength scale, thereby optimizing excitation conditions for ultrasensitive detection. In this work, the control of both analyte and cell positioning on a plasmonic platform is enabled using nanofabrication methods involving patterning of fluorocarbon (FC) polymer (CF) thin films on a plasmonic platform fabricated by nanosphere lithography (NSL).

Thoracolumbar spine model with articulated ribcage for the prediction of dynamic spinal loading.

Musculoskeletal modeling offers an invaluable insight into the spine biomechanics. A better understanding of thoracic spine kinetics is essential for understanding disease processes and developing new prevention and treatment methods. Current models of the thoracic region are not designed for segmental load estimation, or do not include the complex construct of the ribcage, despite its potentially important role in load transmission.

MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images.

Leukocytes Enhance Inflammatory and Catabolic Degenerative Changes in the Intervertebral Disc After Endplate Fracture In Vitro Without Infiltrating the Disc.

Study Design: An established rabbit intervertebral disc (IVD)/endplate explant fracture model was extended with physiologic post-traumatic dynamic loading (PTDL) and coculturing of peripheral blood mononuclear cells (PBMCs).

Objective: The aim of this study was to quantify the effects of PTDL and of cocultured PBMCs on post-traumatic disc degeneration (DD) and to determine whether PTDL facilitates homing of PBMC to fractured IVD/endplates.

Summary Of Background Data: DD is associated with endplate fracture.

Mechanical Predictors of Discomfort during Load Carriage.

Discomfort during load carriage is a major issue for activities using backpacks (e.g. infantry maneuvers, children carrying school supplies, or outdoor sports).

Computational modelling of bone augmentation in the spine.

Computational models are gaining importance not only for basic science, but also for the analysis of clinical interventions and to support clinicians prior to intervention. Vertebroplasty has been used to stabilise compression fractures in the spine for years, yet there are still diverging ideas on the ideal deposition location, volume, and augmentation material. In particular, little is known about the long-term effects of the intervention on the surrounding biological tissue.

Chondrogenic Priming at Reduced Cell Density Enhances Cartilage Adhesion of Equine Allogeneic MSCs - a Loading Sensitive Phenomenon in an Organ Culture Study with 180 Explants.

Background: Clinical results of regenerative treatments for osteoarthritis are becoming increasingly significant. However, several questions remain UNANSWERED concerning mesenchymal stem cell (MSC) adhesion and incorporation into cartilage.

Methods: To this end, peripheral blood (PB) MSCs were chondrogenically induced and/or stimulated with pulsed electromagnetic fields (PEMFs) for a brief period of time just sufficient to prime differentiation.

Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing.

We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compared against regulatory exposure estimates, providing an activity-to-exposure ratio (AER) useful for a risk-based ranking strategy. As ToxCast efforts expand (ie, Phase II) beyond food-use pesticides toward a wider chemical domain that lacks exposure and toxicity information, prediction tools become increasingly important.

Geometrical aspects of patient-specific modelling of the intervertebral disc: collagen fibre orientation and residual stress distribution.

Patient-specific modelling of the spine is a powerful tool to explore the prevention and the treatment of injuries and pathologies. Albeit several methods have been proposed for the discretization of the bony structures, the efficient representation of the intervertebral disc anisotropy remains a challenge, especially with complex geometries. Furthermore, the swelling of the disc's nucleus pulposus is normally added to the model after geometry definition, at the cost of changes of the material properties and an unrealistic description of the prestressed state.

Oriented nanofibrous membranes for tissue engineering applications: Electrospinning with secondary field control.

Electrospinning is an electrical field driven method to produce polymer fibre membranes by deposition of a charged polymer jet onto a grounded collector. Fibre alignment within these mats is usually achieved by a fast collector movement, which is not feasible for all collector geometries, such as small diameter tubes or free-form moulds. The aim of this study was to evaluate the use of charged deflector plates to apply a dynamic, alternating electrical field perpendicular to the spinning direction, in order to directly control the fibre trajectory.

Duration-dependent influence of dynamic torsion on the intervertebral disc: an intact disc organ culture study.

Purpose: Mechanical loading is an important parameter that alters the homeostasis of the intervertebral disc (IVD). Studies have demonstrated the role of compression in altering the cellular metabolism, anabolic and catabolic events of the disc, but little is known how complex loading such as torsion-compression affects the IVD cell metabolism and matrix homeostasis. Studying how the duration of torsion affects disc matrix turnover could provide guidelines to prevent overuse injury to the disc and suggest possible beneficial effect of torsion.

The effect of water on the mechanical properties of soluble and insoluble ceramic cements.

Ceramic cements are good candidates for the stabilization of fractured bone due to their potential ease of application and biological advantages. New formulations of ceramic cements have been tested for their mechanical properties, including strength, stiffness, toughness and durability. The changes in the mechanical properties of a soluble cement (calcium sulfate) upon water-saturation (saturation) was reported in our previous study, highlighting the need to test ceramic cements using saturated samples.

Evaluation of a Novel Screw Position in a Type III Distal Phalanx Fracture Model: An Ex Vivo Study.

Objective: Mechanical evaluation of a novel screw position used for repair in a type III distal phalanx fracture model and assessment of solar canal penetration (SCP).

Study Design: Experimental study.

Sample Population: Disarticulated equine hooves (n = 24) and 24 isolated distal phalanges.