Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women (n = 24; ~27 years, ~23 kg/m2) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following ingestion. We evaluated circulating essential and non-essential amino acids, insulin, and free fatty acids and examined skeletal muscle anabolism by mTORC1 cellular localization, intracellular signaling, and ribosomal profiling. We found that cheese ingestion had a slower yet more sustained branched-chain amino acid circulation appearance over the postprandial period peaking at ~120 min. Cheese also modestly stimulated mTORC1 signaling and increased membrane localization. Using ribosomal profiling we found that, though both milk and cheese stimulated a muscle anabolic program associated with mTORC1 signaling that was more evident with milk, mTORC1 signaling persisted with cheese while also inducing a lower insulinogenic response. We conclude that Cheddar cheese induced a sustained blood amino acid and moderate muscle mTORC1 response yet had a lower glycemic profile compared to milk.

A strategy to passively reduce neuroinflammation surrounding devices implanted chronically in brain tissue by manipulating device surface permeability.

Available evidence indicates that pro-inflammatory cytokines produced by immune cells are likely responsible for the negative sequela associated with the foreign body response (FBR) to chronic indwelling implants in brain tissue. In this study a computational modeling approach was used to design a diffusion sink placed at the device surface that would retain pro-inflammatory cytokines for sufficient time to passively antagonize their impact on the FBR. Using quantitative immunohistochemistry, we examined the FBR to such engineered devices after a 16-week implantation period in the cortex of adult male Sprague-Dawley rats. Our results indicate that thick permeable surface coatings, which served as diffusion sinks, significantly reduced the FBR compared to implants either with no coating or with a thinner coating. The results suggest that increasing surface permeability of solid implanted devices to create a diffusion sink can be used to reduce the FBR and improve biocompatibility of chronic indwelling devices in brain tissue.

Serial section registration of axonal confocal microscopy datasets for long-range neural circuit reconstruction.

In the context of long-range digital neural circuit reconstruction, this paper investigates an approach for registering axons across histological serial sections. Tracing distinctly labeled axons over large distances allows neuroscientists to study very explicit relationships between the brain's complex interconnects and, for example, diseases or aberrant development. Large scale histological analysis requires, however, that the tissue be cut into sections. In immunohistochemical studies thin sections are easily distorted due to the cutting, preparation, and slide mounting processes. In this work we target the registration of thin serial sections containing axons. Sections are first traced to extract axon centerlines, and these traces are used to define registration landmarks where they intersect section boundaries. The trace data also provides distinguishing information regarding an axon's size and orientation within a section. We propose the use of these features when pairing axons across sections in addition to utilizing the spatial relationships among the landmarks. The global rotation and translation of an unregistered section are accounted for using a random sample consensus (RANSAC) based technique. An iterative nonrigid refinement process using B-spline warping is then used to reconnect axons and produce the sought after connectivity information.

Evidence-based indications for ankle arthroscopy.

PURPOSE: The purpose of this study was to review the literature to provide a comprehensive description of the Level of Evidence available to support the surgical technique of ankle arthroscopy for the current generally accepted indications and assign a grade of recommendation for each of them. METHODS: A comprehensive review of the literature was performed (in August 2008) by use of the PubMed database. The abstracts from these searches were reviewed to isolate literature that described therapeutic studies investigating the results of different ankle arthroscopic treatment techniques. All articles were reviewed and assigned a classification (I-IV) of Level of Evidence. An analysis of the literature reviewed was used to assign a grade of recommendation for each current generally accepted indication for ankle arthroscopy. RESULTS: There exists fair evidence-based literature (grade B) to support a recommendation for the use of ankle arthroscopy for the treatment of ankle impingement and osteochondral lesions and for ankle arthrodesis. Ankle arthroscopy for ankle instability, septic arthritis, arthrofibrosis, and removal of loose bodies is supported with only poor-quality evidence (grade C). Treatment of ankle arthritis, excluding isolated bony impingement, is not effective and therefore this indication is not recommended (grade C against). Finally, there is insufficient evidence-based literature to support or refute the benefit of arthroscopy for the management of synovitis and fractures (grade I). CONCLUSIONS: There exists adequate evidence-based literature to support the surgical technique of ankle arthroscopy for most current generally accepted indications; however, further studies in this area are needed. LEVEL OF EVIDENCE: Level IV, systematic review.

The influence of the foreign body response evoked by fibroblast transplantation on soluble factor diffusion in surrounding brain tissue.

The transplantation of genetically engineered fibroblasts has been shown to be an effective approach for achieving continuous and site-specific delivery of therapeutic molecules to various regions of the central nervous system. However, to our knowledge no one has asked whether soluble factors released from the transplanted fibroblasts influence the delivery of therapeutic molecules from the engrafted cells. To address this issue, we used a newly developed cell encapsulation device to study the functional consequence of the foreign body response on soluble factor delivery from fibroblasts transplanted into adult brain tissue. We found that transplanted fibroblasts increased the level of inflammation and glial cell encapsulation at the transplantation site, and reduced the diffusion of a 70 kDa dextran probe through the reactive tissue. The response, however, did not prevent the diffusion of the 70 kDa dextran test probe indicating that the approach appears suitable for the delivery of neurotrophins and other therapeutic molecules with a molecular weight less than 70 kDa. The results suggest that less reactive cell types may be better suited for sustained delivery of therapeutic molecules into brain tissue.

Chronic response of adult rat brain tissue to implants anchored to the skull.

Using quantitative immunohistological methods, we examined the brain tissue response to hollow fiber membranes (HFMs) that were either implanted intraparenchymally, as in a cell encapsulation application, or were attached to the skull as in a biosensor application (transcranially). We found that the reaction surrounding transcranially implanted HFMs was significantly greater than that observed with intraparenchymally implanted materials including increases in immunoreactivity against GFAP, vimentin, ED-1 labeled macrophages and microglia, and several extracellular matrix proteins including collagen, fibronectin, and laminin. In general, these markers were elevated along the entire length of transcranially implanted HFMs extending into the adjacent parenchyma up to 0.5 mm from the implant interface. Intraparenchymal implants did not appear to have significant involvement of a fibroblastic component as suggested by a decreased expression of vimentin, fibronectin and collagen-type I at the implant tissue interface. The increase in tissue reactivity observed with transcranially implanted HFMs may be influenced by several mechanisms including chronic contact with the meninges and possibly motion of the device within brain tissue. Broadly speaking, our results suggest that any biomaterial, biosensor or device that is anchored to the skull and in chronic contact with meningeal tissue will have a higher level of tissue reactivity than the same material completely implanted within brain tissue.