The STRS (shortness of breath, tremulousness, racing heart, and sweating): A brief checklist for acute distress with panic-like autonomic indicators; development and factor structure

Background: Peritraumatic response, as currently assessed by Posttraumatic Stress Disorder (PTSD) diagnostic criterion A2, has weak positive predictive value (PPV) with respect to PTSD diagnosis. Research suggests that indicators of peritraumatic autonomic activation may supplement the PPV of PTSD criterion A2. We describe the development and factor structure of the STRS (Shortness of Breath, Tremulousness, Racing Heart, and Sweating), a one page, two-minute checklist with a five-point Likert-type response format based on a previously unpublished scale. It is the first validated self-report measure of peritraumatic activation of the autonomic nervous system.\ud \ud Methods: We selected items from the Potential Stressful Events Interview (PSEI) to represent two latent variables: 1) PTSD diagnostic criterion A, and 2) acute autonomic activation. Participants (a convenience sample of 162 non-treatment seeking young adults) rated the most distressing incident of their lives on these items. We examined the factor structure of the STRS in this sample using factor and cluster analysis.\ud \ud Results: Results confirmed a two-factor model. The factors together accounted for 68% of the variance. The variance in each item accounted for by the two factors together ranged from 41% to 74%. The item loadings on the two factors mapped precisely onto the two proposed latent variables.\ud \ud Conclusion: The factor structure of the STRS is robust and interpretable. Autonomic activation signs tapped by the STRS constitute a dimension of the acute autonomic activation in response to stress that is distinct from the current PTSD criterion A2. Since the PTSD diagnostic criteria are likely to change in the DSM-V, further research is warranted to determine whether signs of peritraumatic autonomic activation such as those measured by this two-minute scale add to the positive predictive power of the current PTSD criterion A2. Additionally, future research is warranted to explore whether the four automatic activation items of the STRS can be useful as the basis for a possible PTSD criterion A3 in the DSM-V

Reevaluating the Management of Chronic Temporomandibular Pain Are We Treating PTSD with Debridement and Lavage?

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Clinical Researach Histomarkers for Objectively Estimating Premorbid Vagal Tone Chronology in Gulf War Veterans' Illness and in Acute Stres Reaction

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Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

Female Urethral Reconstruction

Female urethral strictures are rare; thus, the literature describing stricture management in women is sparse. Although urethral dilation continues to be performed at a high frequency in women despite lack of proven efficacy, this procedure is used for a variety of voiding complaints other than stricture. Hence, the long-term utility of dilation and urethrotomy for urethral stricture in women is unknown. This review describes the various urethroplasty techniques used in the management of female urethral stricture. Although grafts using a dorsal approach have been shown to be feasible in women, ventral flap techniques offer good long-term outcomes with minimal morbidity. Acute and delayed management of pelvic fracture–associated urethral distraction defects in women is also described. Unlike in men, immediate urethroplasty in women should be performed once the patient is hemodynamically stable

Stat3 Mediates Expression of Autotaxin in Breast Cancer

We determined that signal transducer and activator of transcription 3 (Stat3) is tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired metastatic axillary lymph nodes. Examination of the distribution of tyrosine phosphorylated (pStat3) in primary tumors revealed heterogenous expression within the tumor with the highest levels found in cells on the edge of tumors with relatively lower levels in the central portion of tumors. In order to determine Stat3 target genes that may be involved in migration and metastasis, we identified those genes that were differentially expressed in primary breast cancer samples as a function of pStat3 levels. In addition to known Stat3 transcriptional targets (Twist, Snail, Tenascin-C and IL-8), we identified ENPP2 as a novel Stat3 regulated gene, which encodes autotaxin (ATX), a secreted lysophospholipase which mediates mammary tumorigenesis and cancer cell migration. A positive correlation between nuclear pStat3 and ATX was determined by immunohistochemical analysis of primary breast cancer samples and matched axillary lymph nodes and in several breast cancer derived cell lines. Inhibition of pStat3 or reducing Stat3 expression led to a decrease in ATX levels and cell migration. An association between Stat3 and the ATX promoter, which contains a number of putative Stat3 binding sites, was determined by chromatin immunoprecipitation. These observations suggest that activated Stat3 may regulate the migration of breast cancer cells through the regulation of ATX

A model for uranium, rhenium, and molybdenum diagenesis in marine sediments based on results from coastal locations

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 73 (2009): 2938-2960, doi:10.1016/j.gca.2009.02.029.The purpose of this research is to characterize the mobilization and immobilization processes that control the authigenic accumulation of uranium (U), rhenium (Re) and molybdenum (Mo) in marine sediments. We analyzed these redox– sensitive metals (RSM) in benthic chamber, pore water and solid phase samples at a site in Buzzards Bay, Massachusetts, U.S.A., which has high bottom water oxygen concentrations (230–300 mol/L) and high organic matter oxidation rates (390 mol C/cm2/y). The oxygen penetration depth varies from 2–9 mm below the sediment–water interface, but pore water sulfide is below detection (< 2M). The RSM pore water profiles are modeled with a steady–state diagenetic model that includes irrigation, which extends 10–20 cm below the sediment–water interface. To present a consistent description of trace metal diagenesis in marine sediments, RSM results from sediments in Buzzards Bay are compared with previous research from sulfidic sediments (Morford et al., GCA 71). Release of RSM to pore waters during the remineralization of solid phases occurs near the sediment–water interface at depths above the zone of authigenic RSM formation. This release occurs consistently for Mo at both sites, but only in the winter for Re in Buzzards Bay and intermittently for U. At the Buzzards Bay site, Re removal to the solid phase extends to the bottom of the profile, while the zone of removal is restricted to ~2–9 cm for U and Mo. Authigenic Re formation is independent of the anoxic remineralization rate, which is consistent with an abiotic removal mechanism. The rate of authigenic U formation and its modeled removal rate constant increase with increasing anoxic remineralization rates, and is consistent with U reduction being microbially mediated. Authigenic Mo formation is related to the formation of sulfidic microenvironments. The depth and extent of Mo removal from pore water is closely associated with the balance between iron and sulfate reduction and the consumption of pore water sulfide via iron sulfide formation. Pore water RSM reach constant asymptotic concentrations in sulfidic sediments, but only pore water Re is constant at depth in Buzzards Bay. The increases in pore water U at the Buzzards Bay site are consistent with addition via irrigation and subsequent upward diffusion to the removal zone. Deep pore water Mo concentrations exceed its bottom water concentration due to irrigation–induced oxidation and remobilization from the solid phase. In sulfidic sediments, there is no evidence for higher pore water U or Mo concentrations at depth due to the absence of irrigation and/or the presence of more stable authigenic RSM phases. There are good correlations between benthic fluxes and authigenic accumulation rates for U and Mo in sulfidic sediments. However, results from Buzzards Bay suggest irrigation ultimately results in the partial loss of U and Mo from the solid phase, with accumulation rates that are 20–30% of the modeled flux. Irrigation can augment (Re, possibly U) or compromise (U, Mo) authigenic accumulation in sediments, and is important when determining burial rates in continental margin sediments.The authors also acknowledge financial support from the National Science Foundation (JLM, WRM: OCE–0220892), Research Corporation (JLM, CMC), Franklin & Marshall College, and the Hackman Summer Research Program at F&M

Gamma-Secretase Represents a Therapeutic Target for the Treatment of Invasive Glioma Mediated by the p75 Neurotrophin Receptor

The multifunctional signaling protein p75 neurotrophin receptor (p75NTR) is a central regulator and major contributor to the highly invasive nature of malignant gliomas. Here, we show that neurotrophin-dependent regulated intramembrane proteolysis (RIP) of p75NTR is required for p75NTR-mediated glioma invasion, and identify a previously unnamed process for targeted glioma therapy. Expression of cleavage-resistant chimeras of p75NTR or treatment of animals bearing p75NTR-positive intracranial tumors with clinically applicable γ-secretase inhibitors resulted in dramatically decreased glioma invasion and prolonged survival. Importantly, proteolytic processing of p75NTR was observed in p75NTR-positive patient tumor specimens and brain tumor initiating cells. This work highlights the importance of p75NTR as a therapeutic target, suggesting that γ-secretase inhibitors may have direct clinical application for the treatment of malignant glioma

Trace analysis of environmental matrices by large-volume injection and liquid chromatography-mass spectrometry

The time-honored convention of concentrating aqueous samples by solid-phase extraction (SPE) is being challenged by the increasingly widespread use of large-volume injection (LVI) liquid chromatography–mass spectrometry (LC–MS) for the determination of traces of polar organic contaminants in environmental samples. Although different LVI approaches have been proposed over the last 40 years, the simplest and most popular way of performing LVI is known as single-column LVI (SC-LVI), in which a large-volume of an aqueous sample is directly injected into an analytical column. For the purposes of this critical review, LVI is defined as an injected sample volume that is ≥10% of the void volume of the analytical column. Compared with other techniques, SC-LVI is easier to set up, because it requires only small hardware modifications to existing autosamplers and, thus, it will be the main focus of this review. Although not new, SC-LVI is gaining acceptance and the approach is emerging as a technique that will render SPE nearly obsolete for many environmental applications.In this review, we discuss: the history and development of various forms of LVI; the critical factors that must be considered when creating and optimizing SC-LVI methods; and typical applications that demonstrate the range of environmental matrices to which LVI is applicable, for example drinking water, groundwater, and surface water including seawater and wastewater. Furthermore, we indicate direction and areas that must be addressed to fully delineate the limits of SC-LVI