Examination of the stability of the anxiety sensitivity index across the menstrual cycle in trauma-exposed women with and without PTSD.

Background and Objectives: Anxiety sensitivity (AS), as measured by the Anxiety Sensitivity Index (ASI), has consistently been studied as a trait-level predictor of a variety of emotional and physical health conditions, including premenstrual symptoms. The menstrual cycle influences symptom expression and stress reactivity among anxiety and stress-related disorders. However, research has yet to directly evaluate the stability of AS across the various phases of the menstrual cycle, particularly in clinical populations with high levels of AS and with documented menstrual cycle differences in symptoms such as women with posttraumatic stress disorder (PTSD).Design and Methods: The current study examined whether AS fluctuates as a function of menstrual cycle phase among a community sample of trauma-exposed women (N = 48) with and without PTSD. Participants completed the ASI, including subscales assessing sensitivity to physical, cognitive, and social symptoms of anxiety, during early follicular and mid-luteal menstrual cycle phases.Results: Results revealed that ASI scores remained relatively stable across the different phases of the menstrual cycle assessed; evidence for stability was particularly strong for the subscale assessing sensitivity to physical symptoms of anxiety.Conclusion: This study provides additional support for the conceptualization of AS as a stable, trait-like, cognitive risk factor.

Consecutive Immunohistochemical Staining on a Single Slide is Effective in Confirming Melanocytic Derivation.

BACKGROUND: Metastatic melanoma in sentinel lymph nodes is often elusive to detect with morphology alone. Per American Joint Committee on Cancer staging guidelines, a single atypical melanocyte in lymph node qualifies as metastasis, whether identified by morphology or immunohistochemistry, but single cell staining must be convincing. We propose that the use of a second immunohistochemical run performed on a single slide will allow for more confident diagnosis of micrometastases. MATERIALS AND METHODS: We designed a technical study to determine whether a second antibody application on previously stained slides can successfully detect the same population of cells. Melanocytic neoplasms were stained with SOX-10 using Ventana Benchmark Ultra stainers, coverslipped, and examined, followed by coverslip removal and application of MART-1 (Ventana A103). The order of antibody application and chromagen detection kit (AP-RED vs. DAB) was reversed to establish reliability and robustness of the protocol. RESULTS: All melanocytes marked with SOX-10 and MART-1, and produced a range of staining quality that varied based on order of stain application and chromagen kit were used. The optimal combination was red MART-1 applied first followed by brown SOX-10 applied second. CONCLUSIONS: Consecutive staining of melanocytes with SOX-10 and MART-1 may improve diagnostic confidence of melanocyte identification, particularly in detection of single cell, micrometastases in sentinel lymph nodes or in situations where dual immunohistochemical stains may be unavailable.

Water clarity measures as indicators of recreational benefits provided by U.S. lakes: Swimming and aesthetics.

Lakes provide recreational benefits related to water quality. Using data from the 2007 and 2012 United States National Lake Assessments (N=2067 lake visits), we developed indicators for three benefits: swimming, general recreational value, and aesthetic appeal. For two combined ecoregions ("Mountains" and "Plains") we related objective measures of water clarity, including Secchi depth, turbidity, and water-column chlorophyll-a concentration to subjective visual assessments of recreational benefit quality. There were significant associations between water clarity measures and visual assessments from which we derived water-clarity based thresholds between benefit quality classes (exceptional, high, low, marginal) for each benefit type. More variation in Secchi depth and turbidity was explained by benefit quality than was variation in chlorophyll-a. Threshold values were different between combined ecoregions. Compared to lakes in the Mountains ecoregion, recreational users of Plains lakes have lower expectations for water clarity. Thresholds were generally in accord with water clarity thresholds and guidance derived from published regional studies. Including indicators of the quality of benefits humans receive from lakes in assessments of lake conditions can increase public participation in decision-making and reveal changes in benefit quality over time.

SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as µ opioid ligands.

3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral µ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the µ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.

Activation sequence modification during cardiac resynchronization by manipulation of left ventricular epicardial pacing stimulus strength.

BACKGROUND: Success of cardiac resynchronization therapy (CRT) depends on altering electrical ventricular activation (VA) to achieve mechanical benefit. That increases in stimulus strength (SS) can affect VA has been demonstrated previously in cardiomyopathy patients undergoing ablation. OBJECTIVE: To determine whether increasing SS can alter VA during CRT. METHODS: In 71 patients with CRT devices, left ventricle (LV) pacing was performed at escalating SS. Timing from pacing stimulus to right ventricular (RV) electrogram, ECG morphology, and maximal QRS duration on 12 lead ECG were recorded. DEMOGRAPHICS: Baseline QRS duration 153 +/- 25 ms, ischemic cardiomyopathy 48%, ejection fraction 24%+/- 7%. With increased SS, conduction time from LV to right ventricle (RV) decreased from 125 +/- 56 ms to 111 +/- 59 ms (P = 0.006). QRS duration decreased from 212 +/- 46 ms to 194 +/- 42 ms (P = 0.0002). A marked change in QRS morphology occurred in 11/71 patients (15%). The RV ring was the anode in 6, while the RV coil was the anode in 5. Sites with change in QRS morphology showed decrease in conduction time from LV to RV from 110 +/- 60 ms to 64 +/- 68 ms (P = 0.04). Twelve patients (16%) had diaphragmatic stimulation with increased SS. CONCLUSIONS: Increasing LV SS reduces QRS duration and conduction time from LV to RV. Recognition of significant QRS morphology change is likely clinically important during LV threshold programming to avoid unintended VA change.

Synthesis and characterization of novel poly(ethylene glycol)-lipid conjugates suitable for use in drug delivery.

Liposomal formulations have been used to encapsulate and deliver a wide variety of therapeutic and diagnostic agents. Their circulation can be prolonged by the addition of neutral, hydrophilic polymers such as poly(ethylene glycol) (PEG) to the outer surface. An extended circulation lifetime allows them to take advantage of the enhanced permeability and retention effect (EPR), resulting in increased delivery to target sites. Incorporation of PEG also prevents aggregation and aids in the formation of uniform, small mono-disperse particles. This is often accomplished with the use of PEG-lipid conjugates, PEG molecules with a hydrophobic domain to anchor them into the liposomal bilayer upon formulation. Here we present data showing that some commonly used PEG-lipids are chemically unstable due to the presence of carboxylic ester bonds. This instability limits their utility in aqueous environments common to many liposomal preparations. To address this problem, we designed and synthesized three alternative PEG-lipids. Using SPLP (PEG-stabilized liposomal vesicles encapsulating plasmid DNA) as a model system, we investigated the properties of the novel PEG-lipids. An accelerated stability study was conducted at 37 degrees C for 42 days to confirm chemical stability and an in vivo model was used to assess the pharmacokinetics, toxicity and activity of the SPLP. We show that the novel PEG-lipids are more stable in liposomal formulation, less toxic upon systemic administration, and accordingly, are suitable replacements for the PEG-lipids described previously.