Evolution of the Cross-Sectional Area of the Osseous Lumbar Spinal Canal across Decades: A CT Study with Reference Ranges in a Swiss Population.

Spinal canal dimensions may vary according to ethnicity as reported values differ among studies in European and Chinese populations. Here, we studied the change in the cross-sectional area (CSA) of the osseous lumbar spinal canal measured in subjects from three ethnic groups born 70 years apart and established reference values for our local population. This retrospective study included a total of 1050 subjects born between 1930 and 1999 stratified by birth decade. All subjects underwent lumbar spine computed tomography (CT) as a standardized imaging procedure following trauma. Three independent observers measured the CSA of the osseous lumbar spinal canal at the L2 and L4 pedicle levels. Lumbar spine CSA was smaller at both L2 and L4 in subjects born in later generations (p < 0.001; p = 0.001). This difference reached significance for patients born three to five decades apart. This was also true within two of the three ethnic subgroups. Patient height was very weakly correlated with the CSA at both L2 and L4 (r = 0.109, p = 0.005; r = 0.116, p = 0.002). The interobserver reliability of the measurements was good. This study confirms the decrease of osseous lumbar spinal canal dimensions across decades in our local population

Exploring differential item functioning in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC)

Background: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used patient reported outcome in osteoarthritis. An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items exhibit differential item functioning (DIF). That is, if respondents have the same underlying level of an attribute, does the item give the same score in different subgroups or is it biased towards one subgroup or another. The aim of the study was to explore DIF in the Likert format WOMAC for the first time in a UK osteoarthritis population with respect to demographic, social, clinical and psychological factors. Methods: The sample comprised a community sample of 763 people with osteoarthritis who participated in the Somerset and Avon Survey of Health. The WOMAC was explored for DIF by gender, age, social deprivation, social class, employment status, distress, body mass index and clinical factors. Ordinal regression models were used to identify DIF items. Results: After adjusting for age, two items were identified for the physical functioning subscale as having DIF with age identified as the DIF factor for 2 items, gender for 1 item and body mass index for 1 item. For the WOMAC pain subscale, for people with hip osteoarthritis one item was identified with age-related DIF. The impact of the DIF items rarely had a significant effect on the conclusions of group comparisons. Conclusions: Overall, the WOMAC performed well with only a small number of DIF items identified. However, as DIF items were identified in for the WOMAC physical functioning subscale it would be advisable to analyse data taking into account the possible impact of the DIF items when weight, gender or especially age effects, are the focus of interest in UK-based osteoarthritis studies. Similarly for the WOMAC pain subscale in people with hip osteoarthritis it would be worthwhile to analyse data taking into account the possible impact of the DIF item when age comparisons are of primary interest

The Diagnostic Process of Spinal Post-Traumatic Deformity: An Expert Survey of 7 Cases, Consensus on Clinical Relevance Does Exist

STUDY DESIGN: Survey of cases. OBJECTIVE: To evaluate the opinion of experts in the diagnostic process of clinically relevant Spinal Post-traumatic Deformity (SPTD). SUMMARY OF BACKGROUND DATA: SPTD is a potential complication of spine trauma that can cause decreased function and quality of life impairment. The question of when SPTD becomes clinically relevant is yet to be resolved. METHODS: The survey of 7 cases was sent to 31 experts. The case presentation was medical history, diagnostic assessment, evaluation of diagnostic assessment, diagnosis, and treatment options. Means, ranges, percentages of participants, and descriptive statistics were calculated. RESULTS: Seventeen spinal surgeons reviewed the presented cases. The items\u27 fracture type and complaints were rated by the participants as more important, but no agreement existed on the items of medical history. In patients with possible SPTD in the cervical spine (C) area, participants requested a conventional radiograph (CR) (76%-83%), a flexion/extension CR (61%-71%), a computed tomography (CT)-scan (76%-89%), and a magnetic resonance (MR)-scan (89%-94%). In thoracolumbar spine (ThL) cases, full spine CR (89%-100%), CT scan (72%-94%), and MR scan (65%-94%) were requested most often. There was a consensus on 5 out of 7 cases with clinically relevant SPTD (82%-100%). When consensus existed on the diagnosis of SPTD, there was a consensus on the case being compensated or decompensated and being symptomatic or asymptomatic. CONCLUSIONS: There was strong agreement in 5 out of 7 cases on the presence of the diagnosis of clinically relevant SPTD. Among spine experts, there is a strong consensus to use CT scan and MR scan, a cervical CR for C-cases, and a full spine CR for ThL-cases. The lack of agreement on items of the medical history suggests that a Delphi study can help us reach a consensus on the essential items of clinically relevant SPTD. LEVEL OF EVIDENCE: Level V

An Evolutionary Conserved Role for Anaplastic Lymphoma Kinase in Behavioral Responses to Ethanol

Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention

Role for Circadian Clock Genes in Seasonal Timing: Testing the Bunning Hypothesis

A major question in chronobiology focuses around the “Bünning hypothesis” which implicates the circadian clock in photoperiodic (day-length) measurement and is supported in some systems (e.g. plants) but disputed in others. Here, we used the seasonally-regulated thermotolerance of Drosophila melanogaster to test the role of various clock genes in day-length measurement. In Drosophila, freezing temperatures induce reversible chill coma, a narcosis-like state. We have corroborated previous observations that wild-type flies developing under short photoperiods (winter-like) exhibit significantly shorter chill-coma recovery times (CCRt) than flies that were raised under long (summer-like) photoperiods. Here, we show that arrhythmic mutant strains, per01, tim01 and ClkJrk, as well as variants that speed up or slow down the circadian period, disrupt the photoperiodic component of CCRt. Our results support an underlying circadian function mediating seasonal daylength measurement and indicate that clock genes are tightly involved in photo- and thermo-periodic measurements

Femoral neck fractures after arthroscopic femoral neck osteochondroplasty for femoroacetabular impingement

PURPOSE: The objective of this study was to evaluate the rate, associated risk factors and outcome of insufficiency femoral neck fractures following arthroscopic femoral neck osteochondroplasty for femoroacetabular impingement. METHODS: Between 2005 and 2009, a consecutive series of 376 arthroscopic femoral osteochondroplasties for femoroacetabular impingement were performed and analysed. Seven postoperative fractures were found and comprise the fracture group. The amount of femoral head-neck bone resected as assessed on follow-up cross table lateral views, as well as age, gender, height, weight and BMI, was compared between the fracture group and the entire collective. Subjective outcome was recorded using the WOMAC score. RESULTS: Seven fractures (1.9 %) were identified. All occurred in males at an average of 4.4 weeks postoperatively and were considered insufficiency fractures. The fracture group had a significantly higher mean age (p = 0.01) and height (p = 0.013). Within the fracture group, alpha angles were lower (p = 0.009) and resection depth ratios were higher (p < 0.001). The femoral offset was significantly higher (p = 0.016) in the fracture group and in male patients (p < 0.001). The cut-off value for resection depth ratio on cross table lateral radiograph was 18 % of the femoral head radius. After a mean follow-up of 20 months, an inferior WOMAC (p = 0.030) was recorded in the fracture group. CONCLUSION: Femoral neck insufficiency fractures were identified in 1.9 % of our arthroscopic femoral osteochondroplasty cases. Significant new pain following a period of satisfactory recovery after arthroscopic femoral neck osteochondroplasty should alert the surgeon to the possibility of this complication. If a resection depth ratio of more than 18 % is recognized on the postoperative cross table lateral view, particularly in male patients with a high femoral head-shaft offset, the risk of postoperative insufficiency fracture is increased. This study not only defines the complication rate, but also identifies associated risk factors and determines the influence on the postoperative subjective short-term result. Important information for both the patient and orthopaedic surgeon is provided and may have a direct consequence on the postoperative protocol. LEVEL OF EVIDENCE: IV

Engineering nanoparticles for targeting rheumatoid arthritis: Past, present, and future trends

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint inflammation and cartilage and bone tissue destruction. Although there exist some treatment strategies for RA, they are not completely safe and effective. Therefore, it is important to develop and test new drugs for RA that specifically target inflamed/swollen joints and simultaneously attenuate other possible damages to healthy tissues. Nanotechnology can be a good alternative to consider when envisioning precise medication for treating RA. Through the use of nanoparticles, it is possible to increase bioavailability and bioactivity of therapeutics and enable selective targeting to damaged joints. Herein, recent studies using nanoparticles for the treatment of RA, namely with liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, have been reviewed. These therapeutic strategies have shown great promise in improving the treatment over that by traditional drugs. The results of these studies confirm that feasibility of the use of nanoparticles is mainly due to their biocompatibility, low toxicity, controlled release, and selective drug delivery to inflamed tissues in animal RA models. Therefore, it is possible to claim that nanotechnology will, in the near future, play a crucial role in advanced treatments and patient-specific therapies for human diseases such as RA.Financial support under the ARTICULATE project (No. QREN-13/SI/2011-23189). This study was also funded by the Portuguese Foundation for Science and Technology (FCT) project OsteoCart (No. PTDC/CTM-BPC/115977/2009), as well as the European Union’s FP7 Programme under grant agreement no REGPOT-CT2012-316331-POLARIS. The FCT distinction attributed to J. M. O. under the Investigator FCT program (No. IF/00423/2012) is also greatly acknowledged. C. G. also wished to acknowledge FCT for supporting her research (No. SFRH/BPD/94277/2013)info:eu-repo/semantics/publishedVersio

Circadian oscillator proteins across the kingdoms of life : Structural aspects 06 Biological Sciences 0601 Biochemistry and Cell Biology

Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms and control numerous biological processes in a range of organisms. These periodic rhythms are the result of a complex interplay of interactions among clock components. These components are specific to the organism but share molecular mechanisms that are similar across kingdoms. The elucidation of clock mechanisms in different kingdoms has recently started to attain the level of structural interpretation. A full understanding of these molecular processes requires detailed knowledge, not only of the biochemical and biophysical properties of clock proteins and their interactions, but also the three-dimensional structure of clockwork components. Posttranslational modifications (such as phosphorylation) and protein-protein interactions, have become a central focus of recent research, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. The three-dimensional structures for the cyanobacterial clock components are well understood, and progress is underway to comprehend the mechanistic details. However, structural recognition of the eukaryotic clock has just begun. This review serves as a primer as the clock communities move towards the exciting realm of structural biology