IntroductionLumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes.ObjectivesThe study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed.MethodsA descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster.ResultsMean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool.ConclusionsSNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent.

BackgroundRadiographic features of lumbar disc degeneration (LDD) are common findings in patients with chronic mechanical low back pain; however, its role in disability and intensity of pain is debatable. This study aims to investigate the associations of the x-ray features of LDD and lumbar spondylolisthesis with severity of disability and intensity of pain.MethodsA cross-sectional study was conducted on 439 patients with chronic mechanical low back pain who attended the rheumatology clinic, National Hospital of Sri Lanka, Colombo, from May 2012 to May 2014. Severity of disability was measured using Modified Oswestry Disability Index and intensity of pain was assessed using numeric rating scale (0–100). X-ray features of LDD (disc space narrowing, anterior osteophytes and overall LDD) and spondylolisthesis were assessed in lateral recumbent lumbar x-rays (L1/L2 to L5/S1) and graded by a consultant radiologist blinded to clinical data. Generalised linear model with linear response was used to assess the associations of x-ray features of LDD with severity of disability and intensity of pain adjusting for age, gender, body mass index and pain radiating into legs.ResultsMean age was 48.99 ± 11.21 and 323 (73.58%) were females. 87 (19.82%) were obese. Mean severity of disability was 30.95 ± 13.67 and mean intensity of pain was 45.50 ± 20.37. 69 (15.72%), 26 (5.92%) and 85 (19.36%) patients had grade 2 disc space narrowing, anterior osteophytes and overall LDD, respectively. 51 (11.62%) patients had lumbar spondylolisthesis. Grade of disc space narrowing and overall LDD were not associated with severity of disability or intensity of pain. The presence of lumbar spondylolisthesis was associated with severity of disability. Female gender and pain radiating into legs were associated with severity of disability and intensity of pain. Advancing age was associated with x-ray features of LDD and lumbar spondylolisthesis.ConclusionsLumbar spondylolisthesis is associated with severity of disability in patients with chronic mechanical low back pain. Associations of x-ray features of LDD with severity of disability and intensity of pain are inconclusive. Female gender and pain radiating into legs are significant confounders.

Background Benefits of physical activities are numerous. Barriers for physical exercise may differ among middle aged and older adults. Therefore, identifying and comparing the barriers for participating in regular physical exercises among middle aged and older adults will be useful in designing age specific physical exercise programmes. Methods This descriptive cross sectional study was carried out among 206 Sri Lankan adults in the age range of 40-84 years in the Colombo North region of Sri Lanka using culturally validated questionnaires to determine and compare the barriers and factors associated with regular physical activity participation. Majority were males (56%) and 54% were < 60 years. People in the age range of 40-59 years were considered as middle age and � 60 years as older adults. Bivariate analysis and multivariate analysis was carried out to determine the significant factors that are associated with regular physical activity participation. Results Lack of free time (52%), feeling too lazy (26%) and bad weather (29%) were the main barriers for the participants. In < 60 years, high level of income (p = 0.008) and in � 60 years, being a male (p = 0.016), having a high level of education (P = 0.002) and a high BMI (p = 0.002) had a significant negative association with the level of physical activities. Conclusions Contrary to findings from surveys in several developed countries, this study showed that having a high level of education and being a male were strongly related with lack of physical activity participation.

IntroductionDisc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation.ObjectivesThis study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation.MethodsA descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis.ResultsMean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis.ConclusionsSNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.

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