Relationships Between Eight Measures of Suspect Effort

Previous studies have recommended that multiple measures be employed concurrently to provide converging evidence regarding the presence of suspect effort during neuropsychological assessment. However, if the tests are highly correlated they do not represent independent sources of information. To date, no study has examined correspondence between effort tests. The present study assessed the relationships between eight measures which can be used to assess effort (Rey 15-item, Rey Dot Counting Test, Rey Word Recognition Test, RAVLT recognition trial, Rey-Osterrieth Complex Figure Test effort equation, Digit Span, Warrington Recognition Memory Test-Words, and “b” Test) in a sample of 105 patients in litigation or attempting to obtain/maintain disability compensation and who displayed noncredible symptoms based on psychometric performance and behavioral criteria. Modest to moderate correlations were observed between test summary scores with only two measures sharing more than 50% score variance (Digit Span and Dot Counting). Moderate correlations were also observed between individual test scores reflecting indices of response time, free recall, recognition, and false positive errors, providing possible evidence that patients may use specific strategies when producing noncredible performances. Overall the results suggest that the use of these various tests generally provides nonredundant data regarding patient credibility in neuropsychological evaluations.     

On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet

While the role of collagen and elastin fibrous components in heart valve valvular biomechanics has been extensively investigated, the biomechanical role of the glycosaminoglycan (GAG) gelatinous-like material phase remains unclear. In the present study, we investigated the biomechanical role of GAGs in porcine aortic valve (AV) leaflets under tension utilizing enzymatic removal. Tissue specimens were removed from the belly region of porcine AVs and subsequently treated with either an enzyme solution for GAG removal or a control (buffer with no enzyme) solution. A dual stress level test methodology was used to determine the effects at low and high (physiological) stress levels. In addition, planar biaxial tests were conducted both on-axis (i.e. aligned to the circumferential and radial axes) and at 45° off-axis to induce maximum shear, to explore the effects of augmented fiber rotations on the fiber–fiber interactions. Changes in hysteresis were used as the primary metric of GAG functional assessment. A simulation of the low-force experimental setup was also conducted to clarify the internal stress system and provide viscoelastic model parameters for this loading range. Results indicated that under planar tension the removal of GAGs had no measureable affect extensional mechanical properties (either on- or 45° off-axis), including peak stretch, hysteresis and creep. Interestingly, in the low-force range, hysteresis was markedly reduced, from 35.96 ± 2.65% in control group to 25.00 ± 1.64% (p < 0.001) as a result of GAG removal. Collectively, these results suggest that GAGs do not play a direct role in modulating the time-dependent tensile properties of valvular tissues. Rather, they appear to be strongly connected with fiber–fiber and fiber–matrix interactions at low force levels. Thus, we speculate that GAGs may be important in providing a damping mechanism to reduce leaflet flutter when the leaflet is not under high tensile stress.     

Sex dependent influence of a functional polymorphism in steroid 5‐α‐reductase type 2 (SRD5A2) on post‐traumatic stress symptoms

A non‐synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5‐α‐reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post‐traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African‐American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post‐traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex‐dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex‐specific way, the severity of post‐traumatic stress symptoms and risk for diagnosis of PTSD. © 2013 Wiley Periodicals, Inc.     

Risk of concomitant malignancy in hyperfunctioning adrenal incidentalomas

Background

Adrenal masses are common incidental findings on radiologic imaging. The association between malignancy and hormonal hyperactivity found in incidentally discovered adrenal tumors, however, remains unclear.

Methods

A retrospective analysis of prospectively collected data from patients who underwent adrenalectomy for incidentally discovered adrenal tumors at a single institution. Outcomes and operative data were compared by univariate analysis. Area under the curve was used to analyze the effect of tumor size in predicting malignancy.

Results

There were 49 patients who initially presented with adrenal incidentalomas that underwent adrenalectomy. Most patients were Caucasian women with an average age of 51 ± 14 years. Of this group, 24 patients underwent resection for hyperfunctioning adrenal glands. There were no significant differences in malignancy rates between hyperfunctional and nonfunctional tumors (4.1% vs. 12.0%, P = 0.32). On final histopathology, there were four patients with adrenal malignancies: two adrenocortical carcinomas and two metastatic from renal carcinoma. Only one patient with a hyperfunctioning adrenal tumor had underlying malignancy. Overall, invasion of adjacent structures (P < 0.001), presence of lymphadenopathy (P = 0.02), metastasis (P = 0.03), irregular tumor margins (P = 0.01), heterogeneity (P = 0.05), and tumor size >6 cm (P = 0.04) on radiologic imaging were strongly associated with malignancy in adrenal incidentalomas.

Conclusions

The risk of concomitant malignancy and hormonal hyperactivity in adrenal incidentalomas is very low. Tumor size (>6 cm) and radiographic features remain the most important predictors of adrenal malignancy, regardless of tumor function.     

Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice

PurposeTo characterize the intraocular immune cell infiltrate induced by intravitreal adeno-associated virus (AAV) gene therapy.MethodsAAV vectors carrying plasmids expressing green fluorescent protein under the control of PR2.1 were injected intravitreally into AAV naive and AAV primed C57Bl/6 mice. Clinical inflammation was assessed using optical coherence tomography. Intraocular immune cell populations were identified and quantified by flow cytometry on days 1, 7, and 29 after intravitreal injection and compared with sham and fellow eye controls.ResultsOptical coherence tomography inflammation score and total CD45+ cell number were significantly higher in AAV injected eyes compared to uninjected fellow eye and sham injected controls. Clinically apparent inflammation (vitritis on optical coherence tomography) and cellular inflammation (CD45+ cell number) was significantly increased in AAV injected eyes and peaked around day 7. Vitritis resolved by day 29, but cellular inflammation persisted through day 29. On day 1, neutrophils and activated monocytes were the dominant cell populations in all AAV injected eyes. On day 7, eyes of AAV exposed animals had significantly more dendritic cells and T cells than eyes of AAV naive animals. By day 29, CD8– T cells were the dominant CD45+ cell population in AAV injected eyes.ConclusionsIntravitreal AAV injection in mice generates clinically evident inflammation that is mild and seems to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remain elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.