Delayed perfusion evaluation in extremity trauma.

After severe trauma to an extremity, it is essential to achieve a stable and non-infected wound in order to facilitate the best outcome following reconstruction. That said, timely, meticulous and adequate debridement is very important. To facilitate the best possible debridement of the wound, it is important to understand the tissue circulation. One available method to evaluate tissue circulation following extremity trauma is indocyanine green (ICG) angiography. Though playing an important role in flap surgeries, ICG may also provide information regarding the perfusion at the zone of injury while circulation quality diminishes. We present a case where ICG angiography initially showed good circulation in a mangled extremity, but later used in alternative way to display lack of flow in the same area of interest.

Higher-Order Linearization and Regularity in Nonlinear Homogenization.

We prove large-scale C ∞ regularity for solutions of nonlinear elliptic equations with random coefficients, thereby obtaining a version of the statement of Hilbert's 19th problem in the context of homogenization. The analysis proceeds by iteratively improving three statements together: (i) the regularity of the homogenized Lagrangian  L ¯ , (ii) the commutation of higher-order linearization and homogenization, and (iii) large-scale C 0 , 1 -type regularity for higher-order linearization errors. We consequently obtain a quantitative estimate on the scaling of linearization errors, a Liouville-type theorem describing the polynomially-growing solutions of the system of higher-order linearized equations, and an explicit (heterogenous analogue of the) Taylor series for an arbitrary solution of the nonlinear equations-with the remainder term optimally controlled. These results give a complete generalization to the nonlinear setting of the large-scale regularity theory in homogenization for linear elliptic equations.

A Vascular Malformation in the Hand with Compromised Neurologic Status.

BACKGROUND: Vascular malformations of the hand are rare vascular malformations that are challenging to treat. METHODS: We present a case of a large vascular malformation with left hand pain and decreased sensation of the small and ring fingers. The lesion was treated operatively with surgical excision. RESULTS: The malformation was successfully removed surgically, and pain resolved and numbness recovered by 2 weeks after surgery. CONCLUSIONS: This is a rare case of large vascular malformation in the hand with compromised neurologic status. Surgical treatment provided complete relief of the disease, and the patient returned to normal daily activities.

Integrin α1ß1 participates in chondrocyte transduction of osmotic stress.

BACKGROUND/PURPOSE: The goal of this study was to determine the role of the collagen binding receptor integrin α1ß1 in regulating osmotically induced [Ca(2+)]i transients in chondrocytes. METHOD: The [Ca(2+)]i transient response of chondrocytes to osmotic stress was measured using real-time confocal microscopy. Chondrocytes from wildtype and integrin α1-null mice were imaged ex vivo (in the cartilage of intact murine femora) and in vitro (isolated from the matrix, attached to glass coverslips). Immunocytochemistry was performed to detect the presence of the osmosensor, transient receptor potential vanilloid-4 (TRPV4), and the agonist GSK1016790A (GSK101) was used to test for its functionality on chondrocytes from wildtype and integrin α1-null mice. RESULTS/INTERPRETATION: Deletion of the integrin α1 subunit inhibited the ability of chondrocytes to respond to a hypo-osmotic stress with [Ca(2+)]i transients ex vivo and in vitro. The percentage of chondrocytes responding ex vivo was smaller than in vitro and of the cells that responded, more single [Ca(2+)]i transients were observed ex vivo compared to in vitro. Immunocytochemistry confirmed the presence of TRPV4 on wildtype and integrin α1-null chondrocytes, however application of GSK101 revealed that TRPV4 could be activated on wildtype but not integrin α1-null chondrocytes. Integrin α1ß1 is a key participant in chondrocyte transduction of a hypo-osmotic stress. Furthermore, the mechanism by which integrin α1ß1 influences osmotransduction is independent of matrix binding, but likely dependent on the chondrocyte osmosensor TRPV4.

Circulating tumor cells: clinically relevant molecular access based on a novel CTC flow cell.

BACKGROUND: Contemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available. METHODOLOGY/PRINCIPAL FINDINGS: Recent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error) and a precision (CV<25%) down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL. CONCLUSIONS/SIGNIFICANCE: The LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for clinically relevant genetic profiling of CTCs.

The other gastropod larvae: larval morphogenesis in a marine neritimorph.

Two of the three major gastropod clades with feeding larvae are sister groups and larval morphogenesis for members of these clades, the Caenogastropoda and Heterobranchia, has been well studied. The third clade, the Neritimorpha, has an unstable phylogenetic position and little is known about development of their planktotrophic larvae. Information about larval morphology of neritimorphs and resolution of their controversial phylogenetic placement is critically important for understanding evolution of larval feeding within the Gastropoda. We describe larval morphogenesis to metamorphic competence for laboratory-reared larvae of Nerita melanotragus (Smith, 1884) (Neritimorpha: Neritidae). Preliminary observations suggest that prehatch larvae are capable of delayed hatching, possibly by entering a diapause state. Our description of larval morphogenesis, as based on tissue sections for light and transmission electron microscopy, scanning electron microscopy, three-dimensional-reconstructions of sectioned tissue, and labeling of muscles with fluorphore-tagged phalloidin, revealed four features that are unprecedented among both feeding and nonfeeding gastropod larvae. Larvae of N. melanotragus have muscles on the left and right side that both meet current criteria of a larval retractor muscle; shell-anchored muscles with oblique striations that project inside the visceral nerve loop to insert mainly on the velar lobes. They also have left and right digestive glands of similar size and a left and right hypobranchial gland. A larval "heart" is absent, but water circulation through the mantle cavity may be facilitated by large circular orifices, lined by patches of motile cilia, leading in and out of the mantle cavity. Comparison of larval traits among all three groups of gastropods with feeding larvae indicates that larvae of N. melanotragus have many unique characteristics, but they show more similarities to caenogastropod than to heterobranch larvae. These results are a significant step toward the goal of identifying primitive versus derived larval traits among feeding gastropod larvae.