Mediators and moderators of functional impairment in adults with obsessive–compulsive disorder

The current study examined correlates, moderators, and mediators of functional impairment in 98 treatment-seeking adults with obsessive–compulsive disorder (OCD). Participants completed or were administered measures assessing obsessive–compulsive symptom severity, functional impairment, resistance against symptoms, interference due to obsessive–compulsive symptoms, depressive symptoms, insight, and anxiety sensitivity. Results indicated that all factors, except insight into symptoms, were significantly correlated with functional impairment. The relationship between obsessive–compulsive symptom severity and functional impairment was not moderated by patient insight, resistance against obsessive–compulsive symptoms, or anxiety sensitivity. Mediational analyses indicated that obsessive–compulsive symptom severity mediated the relationship between anxiety sensitivity and obsessive–compulsive related impairment. Indeed, anxiety sensitivity may play an important contributory role in exacerbating impairment through increases in obsessive–compulsive symptom severity. Depressive symptoms mediated the relationship between obsessive–compulsive symptom severity and obsessive–compulsive related impairment. Implications for assessment and treatment are discussed.     

Tonic postganglionic sympathetic inhibition induced by afferent renal nerves?

Other than efferent sympathetic innervation, the kidney has peptidergic afferent fibers expressing TRPV1 receptors and releasing substance P. We tested the hypothesis that stimulation of afferent renal nerve activity with the TRPV1 agonist capsaicin inhibits efferent renal sympathetic nerve activity tonically by a neurokinin 1 receptor-dependant mechanism. Anesthetized Sprague-Dawley rats were instrumented as follows: (1) arterial and venous catheters for recording of blood pressure and heart rate and drug administration; (2) left-sided renal arterial catheter for selective intrarenal administration of the TRPV1 agonist capsaicin (3.3, 6.6, 10, 33*10(-7) m; 10 μL; after 15, 30, 45, and 60 minutes, respectively) to stimulate afferent renal nerve activity; (3) right-sided bipolar electrode for continuous renal sympathetic nerve recording; and (4) specialized renal pelvic and renal artery catheters to separate pelvic from intrarenal afferent activity. Before and after intrarenal capsaicin application, increasing intravenous doses of the neurokinin 1 receptor blocker RP67580 were given. Intrarenal capsaicin decreased integrated renal sympathetic activity from 65.4±13.0 mV*s (baseline) to 12.8±3.2 mV*s (minimum; P<0.01). This sustained renal sympathetic inhibition reached its minimum within 70 minutes and was not directly linked to the transient electric afferent response to be expected with intrarenal capsaicin. Suppressed renal sympathetic activity transiently but completely recovered after intravenous administration of the neurokinin 1 blocker (maximum: 120.3±19.4 mV*s; P<0.01). Intrarenal afferent activity could be unequivocally separated from pelvic afferent activity. For the first time we provide direct evidence that afferent intrarenal nerves provide a tonically acting sympathoinhibitory system, which seems to be rather mediated by neurokinin release acting via neurokinin 1 receptor pathways rather than by electric afferent effects on central sympathetic outflow.     

Elderly Norms for the Hopkins Verbal Learning Test-Revised

The present study evaluates the effects of age, education, and gender in a representative sample of older adults and provides normative data for community-dwelling elderly. Age and gender had significant effects on HVLT-R performance. We provide age- and gender-adjusted normative data. Surprisingly, education level did not affect HVLT-R performance, indicating that education-adjusted norms are not necessary for this measure within this age range. We evaluated a subsample of subjects census-matched on age, education, and gender. These subjects did not differ in overall performance from our entire sample. Therefore, the normative data provided in this paper can be considered to be census-comparable for age, education, and gender.     

Intergenerational Sex as a Risk Factor for HIV Among Young Men Who Have Sex with Men: A Scoping Review

An emerging body of evidence suggests that intergenerational sexual partnerships may increase risk of HIV acquisition among young men who have sex with men (YMSM). However, no studies have comprehensively evaluated literature in this area. We applied a scoping review methodology to explore the relationships between age mixing, HIV risk behavior, and HIV seroconversion among YMSM. This study identified several individual, micro-, and meso-system factors influencing HIV risk among YMSM in the context of intergenerational relationships: childhood maltreatment, coming of age and sexual identity, and substance use (individual-level factors); family and social support, partner characteristics, intimate partner violence, connectedness to gay community (micro-system factors); and race/ethnicity, economic disparity, and use of the Internet (meso-system factors). These thematic groups can be used to frame future research on the role of age-discrepant relationships on HIV risk among YMSM, and to enhance public health HIV education and prevention strategies targeting this vulnerable population.     

Acetabular Cup Design Influences Deformational Response in Total Hip Arthroplasty

Background

Press-fit acetabular components are susceptible to deformation in an underreamed socket, with excessive deformation of metal-on-metal (MOM) components potentially leading to increased torsional friction and micromotion. Specifically, however, it remains unclear how cup diameter, design, and time from implantation affect shell deformation.

Questions/purposes

We asked whether (1) changes in component geometry and material altered maximum shell deformation and (2) time-dependent deformational relaxation processes occurred.

Methods

Diametral deformation was quantified after press-fit implantation of metal shells into a previously validated polyurethane model. Experimental groups (n = 6–8) consisted of 48-, 54-, 60-, and 66-mm MOM cups of 6-mm wall thickness, 58-mm cups of 10-mm wall thickness, and CoCrMo and Ti6Al4V 58-mm modular cups.

Results

Greater cup diameter, thinner wall construction, and Ti6Al4V modular designs generated conditions for maximum shell deformation ranging from 0.047 to 0.267 mm. Relaxation (18%–32%) was observed 120 hours postimplantation in thin-walled and modular designs.

Conclusions

Our findings demonstrate a reduction of shell deformation over time and suggest, under physiologic loading, early component deformation varies with design.

Clinical Relevance

Component deformation should be a design consideration regardless of bearing surface. Designs neglecting to adequately address deformational changes in vivo could be susceptible to diminished cup survival, increased wear, and premature revision.     

Addition of Algenpantucel-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study

Background

Despite continued investigation, limited progress has been made in the adjuvant treatment of resected pancreatic cancer. Novel or targeted therapies are needed.

Methods

Multi-institutional, open-label, dose-finding, phase 2 trial evaluating the use of algenpantucel-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (ClinicalTrials.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survival. Secondary outcomes included overall survival and toxicity.

Results

Seventy patients were treated with gemcitabine and 5-fluorouracil-based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1–14). After a median follow-up of 21 months, the 12-month disease-free survival was 62 %, and the 12-month overall survival was 86 %. The most common adverse events were injection site pain and induration.

Conclusions

The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).     

Effects of training multiple form classes on acquisition,generalization and maintenance of word retrieval in a single subject

Abstract

A study by McNeil et al. reported no generalization effects in two individuals with aphasia following application of a word finding treatment in which subjects were trained sequentially on lexical items arranged by form class. The present investigation examined, in one of the two subjects from the original study, whether training on lexical items from a variety of form classes concurrently would result in greater response generalization than was observed previously in this subject. Results replicated earlier findings with positive acquisition and maintenance effects and little evidence of generalization to untrained items within or across form classes.