Knee Pain Predicts Subsequent Shoulder Pain and the Association Is Mediated by Leg Weakness: Longitudinal Observational Data from the Osteoarthritis Initiative

Objective: To assess whether the ‘spread’ of joint pain is related to pain-associated muscle loss in one joint leading to increased loading and subsequent pain in other joints. Methods: Associations between persistent knee pain (pain in one or two knees over years 0-3 versus no persistent pain) and incident shoulder pain at year 4 were examined in participants from the longitudinal NIH Osteoarthritis Initiative (OAI). Associations were assessed using log multinomial modelling, adjusted for age, sex, BMI, depression score, other lower limb pain and baseline leg weakness (difficulty standing from a sitting position). Results: In older adults with clinically significant knee OA or at risk of knee OA (n=3486), the number of painful joints increased yearly, from 2.1 joints (95% CI 2.0, 2.2) at baseline increasing by 5.2% (95% CI 2.2%, 8.3%) at year 4. Shoulders were the next most commonly affected joint after knees (28.5%). Persistent pain in 1 or 2 knees increased risk of bilateral shoulder pain at year 4 (1 knee RR 1.59 (95% CI 0.97, 2.61); 2 knees RR 2.02 (1.17, 3.49)) after adjustment for confounders. Further adjustment for leg weakness attenuated effect sizes (1 knee RR 1.13 (95% CI 0.60, 2.11); 2 knees RR 1.44 (0.75, 2.77)), indicating mediation by functional leg weakness. Conclusions: Spread of joint pain is not random. Persistently painful knees predict new bilateral shoulder pain, which is likely mediated by leg weakness; suggesting that biomechanical factors influence the spread of pain

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index : a mendelian randomisation study

Objective: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10−7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA

Non-Coding RNA Prediction and Verification in Saccharomyces cerevisiae

Non-coding RNA (ncRNA) play an important and varied role in cellular function. A significant amount of research has been devoted to computational prediction of these genes from genomic sequence, but the ability to do so has remained elusive due to a lack of apparent genomic features. In this work, thermodynamic stability of ncRNA structural elements, as summarized in a Z-score, is used to predict ncRNA in the yeast Saccharomyces cerevisiae. This analysis was coupled with comparative genomics to search for ncRNA genes on chromosome six of S. cerevisiae and S. bayanus. Sets of positive and negative control genes were evaluated to determine the efficacy of thermodynamic stability for discriminating ncRNA from background sequence. The effect of window sizes and step sizes on the sensitivity of ncRNA identification was also explored. Non-coding RNA gene candidates, common to both S. cerevisiae and S. bayanus, were verified using northern blot analysis, rapid amplification of cDNA ends (RACE), and publicly available cDNA library data. Four ncRNA transcripts are well supported by experimental data (RUF10, RUF11, RUF12, RUF13), while one additional putative ncRNA transcript is well supported but the data are not entirely conclusive. Six candidates appear to be structural elements in 5′ or 3′ untranslated regions of annotated protein-coding genes. This work shows that thermodynamic stability, coupled with comparative genomics, can be used to predict ncRNA with significant structural elements

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Efficacy and safety of plant-derived products for the treatment of osteoarthritis

Background: Plant-derived therapies are traditionally used as medicines, but they have generally not been studied with the same rigor as pharmaceutical agents. This review summarizes the use of plant-derived products for osteoarthritis. Methods: Sixty-three identified trials were summarized for pain, function, and safety outcomes using standardized mean differences (SMDs) and relative risks. Results: Plant-derived therapies are effective for treating pain compared to placebo, as assessed using visual analog scores and numerical rating scales (SMD, 1.08; 95% confidence interval [CI]: 0.72–1.44), or Western Ontario and McMaster University Osteoarthritis Index (WOMAC)/Knee injury and Osteoarthritis Outcome Score (KOOS) pain scales (SMD, 0.98; 95% CI: 0.62–1.35). Classes demonstrating overall efficacy in more than one trial for either visual analog scores or WOMAC pain included Boswellia serrata, capsaicin, and ginger; there was single-trial evidence of the efficacy of another nine agents. Plant-derived therapies have similar efficacy to an active comparator (SMD, 0.32; P=0.08; -0.08; P=0.14). Therapies are also effective for functional outcomes compared to placebo (SMD, 0.92; P<0.001). However, significant heterogeneity remains for all pain and function outcomes, indicating that the results need to be interpreted with caution. Risk of adverse events was similar to placebo (relative risk =1.13; P=0.1), but reduced compared to an active comparator (relative risk, 0.75; P<0.001). Conclusion: Plant-derived therapies may be efficacious in treating osteoarthritic pain and functional limitations, and they appear to be safer than other active therapies. However, quality trials and long-term data are lacking, and the number of trials for each therapy is limited. Comparisons would be assisted by trial standardization.20 page(s

A prospective study of the impact of musculoskeletal pain and radiographic osteoarthritis on health related quality of life in community dwelling older people

Background: Pain and radiographic changes are common in persons with osteoarthritis, but their relative contributions to quality of life are unknown.  Methods. Prospective cohort study of 1098 men and women aged 50-80 years, randomly selected from the electoral roll. Participants were interviewed at baseline and approximately 2.6 and five years later. Participants self-reported prior diagnosis of arthritis and presence of joint pain. Joint space narrowing (JSN) and osteophytes at the hip and knee were assessed by X-ray. Quality of life (QoL) was assessed using the Assessment of QoL (AQoL) instrument. Data was analysed using linear regression and mixed modelling.  Results: The median AQoL score at baseline was 7.0, indicating very good QoL. Prevalence of pain ranged from 38-62%. Over five years of observation, pain in the neck, shoulders, back, hips, hands, knees and feet were all independently and negatively associated with QoL, in a dose-response relationship. Diagnosed osteoarthritis at all sites was associated with poorer QoL but after adjustment for pain, this only remained significant at the back. Radiographic OA was not associated with QoL. While AQoL scores declined over five years, there was no evidence of an interaction between pain and time.  Conclusions: Pain is common in older adults, is stable over time, and the strongest musculoskeletal correlate of QoL. It also mediates the association between diagnosed OA and QoL. Since the same factors were associated with quality of life over time as at baseline, this suggests that quality of life tracks over a five year period

The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis

Objective To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 ( TRPV1 ) is associated with genetic risk of painful knee osteoarthritis (OA). Methods The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile–Ile and risk of symptomatic and asymptomatic knee OA was assessed. Results The TRPV1 585 Ile–Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by infl ammatory cytokines (tumour necrosis factor α and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue. Conclusions A genotype involved in lower peripheral pain sensitivity is signifi cantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be infl uenced by a role for this molecule in cartilage function

Longitudinal associations between adiposity and change in knee pain : Tasmanian older adult cohort study

Objective: The aim of this study was to describe the longitudinal relationship between adiposity and change in knee pain. Methods: A total of 1099 participants aged 50-79 were randomly selected from the local community in Southern Tasmania, of which 767 were followed up on average 5.1 years later. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at each time point. Consistent knee pain was defined as knee pain at all three time-points. The five pain subscales were grouped into weight-bearing pain and non-weight-bearing pain according to the nature of pain. Body fat and lean mass were assessed using dual energy x-ray absorptiometry (DXA). Results: Baseline body mass index (BMI) and body fat mass were deleteriously associated with consistent knee pain over follow-up. BMI was consistently associated with increases in weight-bearing and non-weight-bearing pain. Fat mass was associated with an increase in non-weight-bearing pain. In mixed-model analyses, WOMAC total pain score was associated with BMI (β = 1.27) and body fat mass (β = 1.17). The association of lean mass was not significant after adjustment for fat mass. Conclusion: BMI is the most consistent correlate of knee pain in older adults. Fat mass is associated with non-weight-bearing knee pain suggesting systemic mechanisms are involved.6 page(s

Marketing in the company DŘEVOSTAVBY BISKUP, s. r. o.

Tato bakalářská práce je zaměřena na marketingové činnosti. V první části jsou uvedeny teoretické poznatky pro porozumění dané problematice. V druhé části jsou analyzovány marketingové činnosti v podniku DŘEVOSTAVBY BISKUP, s. r. o. Třetí část se zabývá konkrétními návrhy na zlepšení marketingových činnosti v podniku a vyčíslením navrhovaných změn.This bachelor´s thesis is focused on marketing activities. In first part are mentioned theoretic knowledges that are relevant for the understanding the topic. In second part are analyzed marketing acitivities in the company DŘEVOSTAVBY BISKUP, s. r. o. The third part is focused on concrete proposals to improve the marketing activities in the company and quantification of proposed changes.Dopravní fakulta Jana Perner

Change in knee structure and change in tibiofemoral joint space width:A five year longitudinal population-based study

BACKGROUND: Change in knee cartilage volume is frequently used as a proxy for change in knee joint space width over time, but longitudinal data on these associations is limited. We aimed to determine whether change in knee cartilage volume, new or worsening meniscal extrusion (ME), meniscal tears and cartilage defects over 2.4 years correlated with change in joint space width (JSW) over 5 years in older community dwelling adults. METHODS: Participants (n = 153) had their right knee imaged using MR imaging and x-ray at baseline, and after 2.4 years (MRI) and 5 years (x-ray). Cartilage volume, cartilage defects, meniscal extrusions and meniscal tears were assessed on sagittal T1-weighted fat-suppressed MRI. JSW was assessed using standard fixed semi-flexed view radiographs, and scored on those with adequate alignment. RESULTS: Participants were 51–79 (mean 62) years old; 48 % were female. Cartilage volume reduced over time (medial −134 ± 202 μL/year, lateral −106 ± 165 μL/year, p < 0.001), as did JSW (medial −0.05 ± 0.16 mm/year, lateral −0.12 ± 0.24 mm/year, p < 0.001). In multivariable analysis, the only consistent predictor of change in JSW was new or worsening ME (medial tibia R(2) 3.1 %, p = 0.031; medial femur R(2) 3.2 %, p = 0.024); change in cartilage volume correlated with change in JSW laterally (R(2) 4.8 %, p = 0.007) and was borderline medially (R(2) 2.2 %, p = 0.064); there was no association for meniscal tears or cartilage defects. The magnitude of these associations were similar albeit somewhat greater for ME in participants with radiographic OA (R(2) 6.2 %, p = 0.017). CONCLUSION: Change in ME and cartilage volume weakly predict change in JSW, but the vast majority of the variation remains unexplained. Since MRI examines cartilage directly while radiographs examine it indirectly, these results cast doubt on the validity of using JSW as a proxy measure of cartilage loss