The Effect of Sustained Compression on Oxygen Metabolic Transport in the Intervertebral Disc Decreases with Degenerative Changes

Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such relation, relevant to the maintenance of the tissue functional composition, would therefore link disc function with disc nutrition

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Lumbar nerve root injections: a prospective cohort outcomes study comparing age- and gender-matched patients who returned an outcomes-based postal questionnaire with patients who did not return the postal questionnaire

OBJECTIVE: The purpose of this study is to investigate if relying on postal questionnaires returned by patients provides an accurate representation of reported outcomes from patients receiving imaging-guided lumbar nerve root injections (NRIs). MATERIALS AND METHODS: Patients who received imaging-guided transforaminal lumbar NRIs were given short questionnaires inquiring about pain level [numerical rating scale (NRS)] and overall improvement [Patient's Global Impression of Change (PGIC)]. Those who did not return the questionnaires (non-responders) were telephoned and asked about pain level and overall change in condition. Age and gender matching of responders and non-responders resulted in 97 patients in each group. The proportion of patients reporting clinically relevant "improvement" or "worsening" in each group was calculated and the Chi-square test was used to detect differences. NRS and PGIC scores for responders and non-responders were compared using Student's t test and the Mann-Whitney U test, respectively. RESULTS: A higher proportion of non-responders reported clinically relevant improvement (53.6 %) compared to responders (42.6 %) and responders reported significantly higher levels of worsening of condition (p = 0.01). Both responders and non-responders had significant (p ≤ 0.05) improvement on the 20-30-min and 1-month NRS scores compared to their pre-injection baseline scores. Non-responders had significantly higher baseline NRS scores but no significant difference at the 20-30-min and 1-month NRS scores compared to responders. CONCLUSIONS: Patients returning postal questionnaires reported less favorable outcomes compared to those who did not return their questionnaires

Prospective evaluation of two different injection techniques for MR arthrography of the hip

The aim of the study was to evaluate prospectively the technical feasibility and discomfort of two different injection techniques for MR arthrography of the hip. Sixty-one consecutive patients undergoing MR arthrography of the hip (68 hips) were randomly injected either at the femoral head (36 hips) or the femoral neck (32 hips). The patients rated discomfort during and 0-72h after arthrography using a visual analogue scale (VAS, 0="did not feel anything”, 100="unbearable”). The volume injected, the distance between the needle tract and the neurovascular bundle, the duration of the procedure and the extra-articular contrast leakage were measured. No significant differences were found for the volume injected, the distance between the needle tract and the neurovascular bundle, or the procedure duration. Volume of extra-articular contrast leakage was statistically significantly different (head 1±2cm3, neck 3±5cm3, P=0.024). The VAS score for needle advancement was significantly different (head 25±20, neck 19±23, P=0.031). No significant differences were found for the VAS score regarding delayed discomfort. Before the examination the arthrography-related discomfort was overestimated by 74% (50/68), correctly anticipated by 22% (15/68) and underestimated by 4% (3/68) of the patients. MR-related discomfort was overestimated by 32% (22/68), correctly anticipated by 57% (39/68) and underestimated by 10% (7/68) of the patients. Both hip puncture techniques were well tolerated. The neck injection technique produced less discomfort and was associated with greater extra-articular contrast leakag