Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post‐operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze‐drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC‐injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10–12%) viscoelastic moduli after mild degeneration within goats, though the inter‐animal differences were relatively large (complex modulus ～12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at ～75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 703–709, 2013     

Different Recurrence Pattern After Neoadjuvant Chemoradiotherapy Compared to Surgery Alone in Esophageal Cancer Patients

Purpose

To evaluate the rate and pattern of recurrences after neoadjuvant chemoradiotherapy (CRT) in esophageal cancer patients.

Methods

We described survival and differences in recurrences from a single center between neoadjuvant CRT (carboplatin/paclitaxel and 41.4 Gy) and surgery alone for the period 2000–2011. To reduce bias, we performed a propensity score matched analysis.

Results

A total of 204 patients were analyzed, 75 treated with neoadjuvant CRT and 129 with surgery alone. The pathologic response to neoadjuvant CRT was 69 % with a complete response rate of 25 %. After matching, baseline characteristics between the groups (both n = 75) were equally distributed. The 3- and 5-year disease-free survival was 53 and 42 % in the neoadjuvant CRT group compared with 24 and 18 % in the surgery-alone group (P = 0.011). After 3 and 5 years’ CRT, patients had an estimated locoregional recurrence-free survival of 83 and 73 % compared with 52 and 49 % in the surgery-alone group (P = 0.015). The distant recurrence-free survival was comparable in both groups. Locoregional recurrences were located less in the paraesophageal lymph nodes in the CRT group than in the surgery-alone group, 9 versus 21 %, respectively (P = 0.041). With respect to differences in distant recurrences, we observed more skeletal recurrences in the surgery-alone group compared to CRT, 12 versus 1 % (P = 0.009).

Conclusions

The neoadjuvant CRT regimen we used offers a significant improvement in outcome, with a different recurrence pattern compared with surgery alone. This effect is probably due to both the pathologic complete response and eradication of micrometastases in CRT group.     

Exposure to secondhand smoke and depression and anxiety: A report from two studies in the Netherlands

Objective

Previous population-based studies suggest that exposure to secondhand smoke (SHS) is related to increased depressive symptoms and poor mental health among non-smokers. We examined whether these associations could be replicated in two independent Dutch samples.

Methods

Non-smoking adults were selected from two studies: 1) the Netherlands Study of Depression and Anxiety (NESDA), comprising individuals with current and remitted depressive and/or anxiety disorders, and healthy controls and 2) the Netherlands Twin Register (NTR), comprising twin-family studies on health-related behaviors. In both studies, SHS exposure was assessed with plasma cotinine levels (1–14 ng/ml vs. < 1 ng/ml). In NESDA, outcomes were current depressive and/or anxiety disorders, and depression and anxiety symptom severity scores. In NTR, the Adult Self Report derived DSM-subscales for depressive and anxiety problems, and anxious depressive scores were analyzed.

Results

In NESDA non-smokers (n = 1757), increased plasma cotinine level (≥ 1 ng/ml) was not related to current depressive and/or anxiety disorders [odds ratio (OR) 0.96, P = .77], nor to depression or anxiety severity indicators. Similarly, in NTR non-smokers (n = 1088) cotinine levels ≥ 1 ng/ml were not associated with the DSM-subscale for depressive problems [unstandardized regression coefficient (B) 0.04, P = .88], nor to other depression and anxiety measures.

Conclusions

In non-smoking adults from patient and population samples, we found no evidence that plasma cotinine levels were related to either depressive and/or anxiety disorders, or to depressive and anxiety symptoms. This suggests that SHS exposure is not related to depression and anxiety in non-smoking adults.     

The relation between frontal EEG asymmetry and the risk for anxiety and depression

Frontal asymmetry of EEG alpha power (FA) may index the risk for anxiety and depression. Evidence linking FA to the underlying biological mechanisms is scarce. This is unfortunate because FA has potential as a biological marker to support gene finding in anxiety and depression. We examined the heritability of FA in 732 twins and their singleton siblings, and established the genetic and environmental contribution to the relation between FA and the risk for anxiety and depression. Multivariate models showed that FA is heritable only in young adults (males 32% and females 37%) but not in middle-aged adults. A significant relation between FA and the risk for anxiety and depression was only found in young adult females. This relation was explained by shared genes influencing both EEG and disease risk. Future studies on asymmetry of left and right frontal brain activation should carefully consider the effects of sex and age.