Disabling knee pain – another consequence of obesity: Results from a prospective cohort study

BACKGROUND: Obesity is linked to knee osteoarthritis (OA) and knee pain. These are disabling problems that are more prevalent in older adults. No prospective study has estimated the impact of excess weight avoidance on the occurrence of knee pain in the general older population. The aim of this study was to investigate the influence of overweight and obesity on the onset and progression of knee pain and disability in older adults living in the community. METHODS: A prospective cohort study of people aged 50 and over registered with three general practices in North Staffordshire, UK. 5784 people who had responded to a survey in March 2000 were mailed a follow-up questionnaire in March 2003. The main outcome measures were self-reported knee pain and severe knee pain and disability at 3 years measured by the Western Ontario and McMaster Universities Osteoarthritis index. RESULTS: Adjusted response to follow-up was 75%. Among responders with no knee pain at baseline, obesity predicted onset of severe knee pain (relative risk 2.8; 95% CI 1.8, 4.5 compared to normal body mass index (BMI) category). Considering overweight and obese categories together, 19% of new cases of severe knee pain over a 3-year period could potentially be avoided by a one-category shift downwards in BMI; this includes almost half of the new cases that arose in the obese group. CONCLUSION: Obesity accounts for a substantial proportion of severe disabling knee pain. As knee pain is a common disabling condition in older adults living in the community, effective public health interventions about avoidance of excess weight could have a major impact on future lower limb disability in older adults

Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

Mx Scripts Library: Structural Equation Modeling Scripts for Twin and Family Data

Structural equation modeling (SEM) provides a flexible tool to carry out genetic analyses of family and twin data. The basic model which decomposes the variance between and within families for a particular trait into genetic and non-genetic components can be generalized to multivariate and/ or longitudinal data, incorporate sex differences in parameter estimates, and model the effects of measured environment, candidate genes or DNA marker data. We introduce a web-based library ( http://www.psy.vu.nl/mxbib ) of scripts for uni- and multivariate genetic epidemiological analyses, as well as for linkage and genetic association tests. The scripts are written to be used with the freely available software package Mx and provide a flexible and uniform approach to the analysis of data from relatives. © 2005 Springer Science+Business Media, Inc

The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population: baseline recruitment and retention at 18 months

BACKGROUND: Selective non-participation at baseline (due to non-response and non-consent) and loss to follow-up are important concerns for longitudinal observational research. We investigated these matters in the context of baseline recruitment and retention at 18 months of participants for a prospective observational cohort study of knee pain and knee osteoarthritis in the general population. METHODS: Participants were recruited to the Knee Clinical Assessment Study – CAS(K) – by a multi-stage process involving response to two postal questionnaires, consent to further contact and medical record review (optional), and attendance at a research clinic. Follow-up at 18-months was by postal questionnaire. The characteristics of responders/consenters were described for each stage in the recruitment process to identify patterns of selective non-participation and loss to follow-up. The external validity of findings from the clinic attenders was tested by comparing the distribution of WOMAC scores and the association between physical function and obesity with the same parameters measured directly in the target population as whole. RESULTS: 3106 adults aged 50 years and over reporting knee pain in the previous 12 months were identified from the first baseline questionnaire. Of these, 819 consented to further contact, responded to the second questionnaire, and attended the research clinics. 776 were successfully followed up at 18 months. There was evidence of selective non-participation during recruitment (aged 80 years and over, lower socioeconomic group, currently in employment, experiencing anxiety or depression, brief episode of knee pain within the previous year). This did not cause significant bias in either the distribution of WOMAC scores or the association between physical function and obesity. CONCLUSION: Despite recruiting a minority of the target population to the research clinics and some evidence of selective non-participation, this appears not to have resulted in significant bias of cross-sectional estimates. The main effect of non-participation in the current cohort is likely to be a loss of precision in stratum-specific estimates e.g. in those aged 80 years and over. The subgroup of individuals who attended the research clinics and who make up the CAS(K) cohort can be used to accurately estimate parameters in the reference population as a whole. The potential for selection bias, however, remains an important consideration in each subsequent analysis

Acceptability of, and preferences for, remote consulting during COVID-19 among older patients with two common long-term musculoskeletal conditions: findings from three qualitative studies and recommendations for practice

BackgroundGuidance for choosing face-to-face vs remote consultations (RCs) encourages clinicians to consider patient preferences, however, little is known about acceptability of, and preferences for RCs, particularly amongst patients with musculoskeletal conditions. This study aimed to explore the acceptability of, and preferences for, RC among patients with osteoporosis and rheumatoid arthritis.MethodsThree UK qualitative studies, exploring patient experiences of accessing and receiving healthcare, undertaken during the pandemic, with people with osteoporosis and rheumatoid arthritis. Study team members agreed a consistent approach to conduct rapid deductive analysis using the Theoretical Framework of Acceptability (TFA) on transcripts from each data set relating to RC, facilitated by group meetings to discuss interpretations. Findings from the three studies were pooled.ResultsFindings from 1 focus group and 64 interviews with 35 people were included in the analysis. Participants’ attitudes to RC, views on fairness (ethicality) and sense-making (intervention coherence) varied according to their needs within the consultation and views of the pandemic. Some participants valued the reduced burden associated with RC, while others highly valued non-verbal communication and physical examination associated with face-to-face consults (opportunity costs). Some participants described low confidence (self-efficacy) in being able to communicate in RCs and others perceived RCs as ineffective, in part due to suboptimal communication.Conclusions Acceptability of, and preferences for RC appear to be influenced by societal, healthcare provider and personal factors and in this study, were not condition-dependant. Remote care by default has the potential to exacerbate health inequalities and needs nuanced implementation

Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS)

BACKGROUND: Self-reported knee complaints may vary with age and gender. Reference data from the adult population would help to better interpret the outcome of interventions due to knee complaints. The objectives of the present study were to describe the variation of self-reported knee pain, function and quality of life with age and gender in the adult population and to establish population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). METHODS: Population-based cohort retrieved from the national population register. The knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) was mailed to 840 subjects aged 18–84 yrs. RESULTS: 68% response rate. Women in the age group 55–74 reported more knee-related complaints in all the KOOS subscales than age-matched men. The differences were significant for the subscales Pain (p = 0.027), Symptoms (p = 0.003) and ADL function (p = 0.046). In men, worse ADL and Sport and Recreation function was seen in the oldest age group 75–84 years compared to the younger age groups (p < 0.030). In women, worse Pain (p < 0.007), ADL (p < 0.030), Sport and Recreation (p < 0.001) and QOL (p < 0.002) were seen already in the age group 55–74 compared to the younger age groups. CONCLUSION: We found pain and other symptoms, physical function, and knee-related quality of life to vary with age and gender implying the use of age- and gender matched reference values for improved understanding of the outcome after interventions due to knee injury and knee OA

The Genetic Basis of Heterosis: Multiparental Quantitative Trait Loci Mapping Reveals Contrasted Levels of Apparent Overdominance Among Traits of Agronomical Interest in Maize (Zea mays L.)

Understanding the genetic bases underlying heterosis is a major issue in maize (Zea mays L.). We extended the North Carolina design III (NCIII) by using three populations of recombinant inbred lines derived from three parental lines belonging to different heterotic pools, crossed with each parental line to obtain nine families of hybrids. A total of 1253 hybrids were evaluated for grain moisture, silking date, plant height, and grain yield. Quantitative trait loci (QTL) mapping was carried out on the six families obtained from crosses to parental lines following the “classical” NCIII method and with a multiparental connected model on the global design, adding the three families obtained from crosses to the nonparental line. Results of the QTL detection highlighted that most of the QTL detected for grain yield displayed apparent overdominance effects and limited differences between heterozygous genotypes, whereas for grain moisture predominance of additive effects was observed. For plant height and silking date results were intermediate. Except for grain yield, most of the QTL identified showed significant additive-by-additive epistatic interactions. High correlation observed between heterosis and the heterozygosity of hybrids at markers confirms the complex genetic basis and the role of dominance in heterosis. An important proportion of QTL detected were located close to the centromeres. We hypothesized that the lower recombination in these regions favors the detection of (i) linked QTL in repulsion phase, leading to apparent overdominance for heterotic traits and (ii) linked QTL in coupling phase, reinforcing apparent additive effects of linked QTL for the other traits

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (&#8805; 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified