Wound healing monitoring using near infrared fluorescent fibrinogen

We demonstrate a method for imaging the wound healing process with near infrared fluorescent fibrinogen. Wound healing studies were performed on a rat punch biopsy model. Fibrinogen was conjugated with a near infrared fluorescent dye and injected into the tail vein. Fibrinogen is a useful protein for tracking wound healing because it is involved in fibrin clot formation and formation of new provisional matrix through transglutaminase’s crosslinking activity. Strong fluorescence specific to the wound was observed and persisted for several days, indicating that the fibrinogen is converted to crosslinked fibrin. Administration of contrast agent simultaneously with wound creation led to primary labeling of the fibrin clot, indicating that the wound was in its early phase of healing. Administration on the following day showed labeling on the wound periphery, indicating location of formation of a new provisional matrix. This method may prove to be useful as a diagnostic for basic studies of the wound healing process, in drug development, or in clinical assessment of chronic wounds

Pairing of Parafermions of Order 2: Seniority Model

As generalizations of the fermion seniority model, four multi-mode Hamiltonians are considered to investigate some of the consequences of the pairing of parafermions of order two. 2-particle and 4-particle states are explicitly constructed for H_A = - G A^+ A with A^+}= 1/2 Sum c_{m}^+ c_{-m}^+ and the distinct H_C = - G C^+ C with C^+}= 1/2 Sum c_{-m}^+ c_{m}^+, and for the time-reversal invariant H_(-)= -G (A^+ - C^+)(A-C) and H_(+) = -G (A^+dagger + C^+)(A+C), which has no analogue in the fermion case. The spectra and degeneracies are compared with those of the usual fermion seniority model.Comment: 18 pages, no figures, no macro

Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide

Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties. We find that tumor necrosis factor-α-stimulated neutrophil adherence is opposed by TG2 molecules that are bound to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial surfaces restores the anti-inflammatory properties of the endothelium, and reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2 is present in healthy tissues and that it forms on the membranes of shear-activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface

Evidence of Fragmenting Dust Particles from Near-Simultaneous Optical and Near-IR Photometry and Polarimetry of Comet 73P/Schwassmann-Wachmann 3

We report imaging polarimetry of segments B and C of the Jupiter-family Comet 73P/Schwassmann-Wachmann 3 in the I and H bandpasses at solar phase angles of approximately 35 and 85deg. The level of polarization was typical for active comets, but larger than expected for a Jupiter-family comet. The polarimetric color was slightly red (dP/dL = +1.2 +/- 0.4) at a phase angle of ~ 35deg and either neutral or slightly blue at a phase angle of ~ 85deg. Observations during the closest approach from 2006 May 11-13 achieved a resolution of 35 km at the nucleus. Both segments clearly depart from a 1/rho surface brightness for the first 50 - 200 km from the nucleus. Simulations of radiation driven dust dynamics can reproduce some of the observed coma morphology, but only with a wide distribution of initial dust velocities (at least a factor of 10) for a given grain radius. Grain aggregate breakup and fragmentation are able to reproduce the observed profile perpendicular to the Sun-Comet axis, but fit the observations less well along this axis (into the tail). The required fragmentation is significant, with a reduction in the mean grain aggregate size by about a factor of 10. A combination of the two processes could possibly explain the surface brightness profile of the comet.Comment: 40 pages including 11 figure

High Healthcare Utilization at the Onset of Medically Unexplained Symptoms

Objective: Patients with medically unexplained syndromes (MUS) often do not receive appropriate healthcare. A critical time for effective healthcare is the inception of MUS. The current study examined data from a prospective longitudinal study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans to understand the relationship of increasing physical symptom burden to healthcare utilization. Methods: Data was examined from a prospective study of OEF/OIF veterans assessed before and one year after deployment (n=335). Physical symptom burden was measured with the Patient Health Questionnaire (PHQ-15). Analyses were conducted with polynomial regression and response surface analysis (RSA). Results: Increases in physical symptom burden predicted greater healthcare utilization one year after deployment: primary care practitioner (slope = -0.26, F=4.07, p=0.04), specialist (slope = -.43, t=8.67, p=0.003), allied health therapy (e.g., physical therapy) (slope = -.41, t=5.71, p=0.02) and mental health (slope = -.32, F=4.04, p=0.05). There were no significant difference in utilization between those with consistently high levels and those with increases in physical symptom burden. Conclusion: This is the first prospective study to examine, and show, a relationship between onset of clinically significant physical symptoms and greater healthcare utilization. Our data suggest that patients with increasing physical symptom burden have the same level of healthcare as patients with chronic physical symptom burden. Needed next steps are to better understand the quality of care at inception and determine how to intervene so that recommended approaches to care are provided from the onset

Passive sampling methods for contaminated sediments: Risk assessment and management

This paper details how activity-based passive sampling methods (PSMs), which provide information on bioavailability in terms of freely dissolved contaminant concentrations (Cfree), can be used to better inform risk management decision making at multiple points in the process of assessing and managing contaminated sediment sites. PSMs can increase certainty in site investigation and management, because Cfree is a better predictor of bioavailability than total bulk sediment concentration (Ctotal) for 4 key endpoints included in conceptual site models (benthic organism toxicity, bioaccumulation, sediment flux, and water column exposures). The use of passive sampling devices (PSDs) presents challenges with respect to representative sampling for estimating average concentrations and other metrics relevant for exposure and risk assessment. These challenges can be addressed by designing studies that account for sources of variation associated with PSMs and considering appropriate spatial scales to meet study objectives. Possible applications of PSMs include: quantifying spatial and temporal trends in bioavailable contaminants, identifying and evaluating contaminant source contributions, calibrating site-specific models, and, improving weight-of-evidence based decision frameworks. PSM data can be used to assist in delineating sediment management zones based on likelihood of exposure effects, monitor remedy effectiveness, and, evaluate risk reduction after sediment treatment, disposal, or beneficial reuse after management actions. Examples are provided illustrating why PSMs and freely dissolved contaminant concentrations (Cfree) should be incorporated into contaminated sediment investigations and study designs to better focus on and understand contaminant bioavailability, more accurately estimate exposure to sediment-associated contaminants, and better inform risk management decisions. Research and communication needs for encouraging broader use are discussed. Integr Environ Assess Manag 2014;10:224–236. © 2014 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility