Post-Event Processing in Social Anxiety Disorder: Idiosyncratic Priming in the Course of CBT

Post-event processing (PEP) is the cognitive rumination that follows social events for patients with social anxiety. The PEP period was examined in relation to two anxiety provoking tasks in cognitive behavioural group therapy for social anxiety disorder: (1) Attending the first group therapy session (n = 75), and (2) An individually tailored in-session exposure task (n = 50). An assessment of PEP was conducted the week following each task as an indication of the extent of rumination over that event during the subsequent week. Significant PEP occurred after both events, and greater baseline social anxiety predicted greater levels of PEP related to both tasks. Anxiety ratings, as conceptualized by SUDS, were positively correlated with the severity of subsequent PEP related to the exposure task. There was also support for the stability of PEP across the two tasks and for the specificity of the content of PEP as rumination related to social failure, rather than rumination related to depressive symptoms. This study provides additional empirical support for the role of PEP in the cognitive model of social anxiety disorder.     

Progress in prion vaccines and immunotherapies

The transmissible spongiform encephalopathies have presented a challenge to physicians and scientists attempting to develop immunologically-based treatments. Self-tolerance has been one of the major obstacles to successfully raising antibodies against the prion protein (PrP), the host-encoded protein whose misfolded form (PrPSc) is linked to the protein-only infectious agent responsible for these disorders. Recently, it has been shown that antibodies directed against the normal cellular isoform of PrP (PrPC) can reduce or eliminate PrP isoform conversion in both in vitro and in vivo model systems. Similar studies with a PrPSc-specific epitope target are in progress. There is now rational hope that this devastating group of diseases may soon be amenable to immunotherapy and immunoprophylaxis.     

Glucuronidation of monohydroxylated warfarin metabolites by human liver microsomes and human recombinant UDP-glucuronosyltransferases

Our understanding of human phase II metabolic pathways which facilitate detoxification and excretion of warfarin (Coumadin) is limited. The goal of this study was to test the hypothesis that there are specific human hepatic and extrahepatic UDP-glucuronosyltransferase (UGT) isozymes, which are responsible for conjugating warfarin and hydroxylated metabolites of warfarin. Glucuronidation activity of human liver microsomes (HLMs) and eight human recombinant UGTs toward (R)- and (S)-warfarin, racemic warfarin, and major cytochrome P450 metabolites of warfarin (4'-, 6-, 7-, 8-, and 10-hydroxywarfarin) has been assessed. HLMs, UGT1A1, 1A8, 1A9, and 1A10 showed glucuronidation activity toward 4'-, 6-, 7-, and/or 8-hydroxywarfarin with K(m) values ranging from 59 to 480 microM and V(max) values ranging from 0.03 to 0.78 microM/min/mg protein. Tandem mass spectrometry studies and structure comparisons suggested glucuronidation was occurring at the C4'-, C6-, C7-, and C8-positions. Of the hepatic UGT isozymes tested, UGT1A9 exclusively metabolized 8-hydroxywarfarin, whereas UGT1A1 metabolized 6-, 7-, and 8-hydroxywarfarin. Studies with extrahepatic UGT isoforms showed that UGT1A8 metabolized 7- and 8-hydroxywarfarin and that UGT1A10 glucuronidated 4'-, 6-, 7-, and 8-hydroxywarfarin. UGT1A4, 1A6, 1A7, and 2B7 did not have activity with any substrate, and none of the UGT isozymes evaluated catalyzed reactions with (R)- and (S)-warfarin, racemic warfarin, or 10-hydroxywarfarin. This is the first study identifying and characterizing specific human UGT isozymes, which glucuronidate major cytochrome P450 metabolites of warfarin with similar metabolic rates known to be associated with warfarin metabolism. Continued characterization of these pathways may enhance our ability to reduce life-threatening and costly complications associated with warfarin therapy.     

The practical management of artifact in computerised physiological data

Computerised physiological data contains artifact that needs to be identified and possibly removed. Whilst computers may eventually satisfactorily perform this function, at present only manual removal is possible for the majority of intensive care computer groups. We assessed the effects of artifact and its removal on the physiological data of 3 patients. Artifact was manually removed from 7 days of data in 4 parameters (heart rate, respiratory rate, systolic blood pressure [sbp] and transcutaneous oxygen [tcpO2]) by 3 independent observers. Six hour time periods were analysed. Median and mean values before and after the manual removal of artifact were compared. Overall. 6.5% of data was removed as artifact. This was greatest for tcp02 (9.9%) and sbp (10.6%), with smaller amounts for respiratory rate (2.8%) and heart rate (2.4%). Sbp showed a marked difference in the amount of data removed between patients, whereas tcp02 data contained quite large volumes of artifact, but this was fairly consistent between patients, Removal of artifact affected mean values more than median values. One observer considered that both physiological and non-physiological artifact should be removed, whereas the other two observers removed only non-physiological artifact. Agreement in results between the latter was good. Our results suggest that interobserver variability should have a minimal effect on values, once rules identifying the type of artifact to be removed are agreed. Removal of artifact did not have a clinically significant effect on results, but may be an important consideration in the statistical analysis of computerised physiological data.Abbreviations CPTM computerised physiological trend monitoring - tcp02 transcutaneous pressure of oxygen - sbp systolic blood pressure     

Organization of sensory input to the nociceptive‐specific cutaneous trunk muscle reflex in rat,an effective experimental system for examining nociception and plasticity

Detailed characterization of neural circuitries furthers our understanding of how nervous systems perform specific functions and allows the use of those systems to test hypotheses. We have characterized the sensory input to the cutaneous trunk muscle (CTM; also cutaneus trunci [rat] or cutaneus maximus [mouse]) reflex (CTMR), which manifests as a puckering of the dorsal thoracolumbar skin and is selectively driven by noxious stimuli. CTM electromyography and neurogram recordings in naïve rats revealed that CTMR responses were elicited by natural stimuli and electrical stimulation of all segments from C4 to L6, a much greater extent of segmental drive to the CTMR than previously described. Stimulation of some subcutaneous paraspinal tissue can also elicit this reflex. Using a selective neurotoxin, we also demonstrate differential drive of the CTMR by trkA‐expressing and nonexpressing small‐diameter afferents. These observations highlight aspects of the organization of the CTMR system that make it attractive for studies of nociception and anesthesiology and plasticity of primary afferents, motoneurons, and the propriospinal system. We use the CTMR system to demonstrate qualitatively and quantitatively that experimental pharmacological treatments can be compared with controls applied either to the contralateral side or to another segment, with the remaining segments providing controls for systemic or other treatment effects. These data indicate the potential for using the CTMR system as both an invasive and a noninvasive quantitative assessment tool providing improved statistical power and reduced animal use. J. Comp. Neurol. 522:1048–1071, 2014. © 2013 Wiley Periodicals, Inc.     

Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer

ObjectivesTreating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP.Materials and methodsThe Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level >20 ng/ml or Gleason score 8–10 or stage>cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy.ResultsCompared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56–0.64; P<0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P_interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P<0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P<0.001) among insured men.ConclusionsAA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.     

Determinants of Repeat Curative Intent Surgery in Colorectal Liver Metastasis

Introduction

Following curative intent surgery (CIS) for colorectal liver metastasis (CRLM), repeat CIS for recurrence improves survival. The factors associated with repeat CIS are not widely reported.

Methods

An institutional database (January 2002–December 2012) was reviewed to evaluate factors influencing repeat CIS.

Results

One hundred sixty-three patients with colorectal liver metastasis (CRLM) underwent successful CIS. Median follow-up and disease-free interval (DFI) was 33 and 16 months, respectively. After initial CIS, 102 patients (63 %) recurred. Fifty-three patients (52 %) underwent a repeat CIS. After repeat CIS, 33 patients (62 %) developed a second recurrence, and in 13 patients (39 %), a third CIS was possible. DFI decreased following initial CIS (first CIS vs. second CIS vs. third CIS [20 vs. 15 vs. 8.5 months], p?Conclusion Despite high recurrence and decreasing DFI, repeat CIS provides a survival benefit. Postoperative complications, DFI, number, and pattern of recurrence influence the decision to pursue repeat CIS.