The PDZ domain-containing sorting nexin 27 (SNX27) promotes recycling of internalized transmembrane proteins from endosomes to the plasma membrane by linking PDZ-dependent cargo recognition to retromer-mediated transport. Here, we employed quantitative proteomics of the SNX27 interactome alongside quantification of the surface proteome of SNX27 and retromersuppressed cells to dissect the assembly of the SNX27 complex and provide an unbiased global view of SNX27-mediated sorting. Over 100 cell surface proteins, many of which interact with SNX27, including the glucose transporter GLUT1, the Menkes disease copper transporter ATP7A, various zinc and amino acid transporters, and numerous signalling receptors require SNX27-retromer to prevent lysosomal degradation and maintain surface levels. Furthermore, we establish that direct interaction of the SNX27 PDZ domain with the retromer subunit VPS26 is necessary and sufficient to prevent lysosomal entry of SNX27 cargo. Our data identify the SNX27-retromer as a major endosomal recycling hub required to maintain cellular nutrient homeostasis.

These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.

Objectives: To investigate the claim that 90% of episodes of low back pain that present to general practice have resolved within one month. Design: Prospective study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week, 3 months, and 12 months after consultation. Setting: Two general practices in south Manchester. Subjects: 490 subjects (203 men, 287 women) aged 18-75 years. Main outcome measures: Proportion of patients who have ceased to consult with low back pain after 3 months; proportion of patients who are free of pain and back related disability at 3 and 12 months. Results: Annual cumulative consultation rate among adults in the practices was 6.4%. Of the 463 patients who consulted with a new episode of low back pain, 275 (59%) had only a single consultation, and 150 (32%) had repeat consultations confined to the 3 months after initial consultation. However, of those interviewed at 3 and 12 months follow up, only 39/188 (21%) and 42/170 (25%) respectively had completely recovered in terms of pain and disability. Conclusions:The results are consistent with the interpretation that 90% of patients with low back pain in primary care will have stopped consulting with symptoms within three months. However most will still be experiencing low back pain and related disability one year after consultation.

Objectives To quantify the relative contribution of premorbid and episode specific factors in determining the long term persistence of disabling symptoms of low back pain.

The objective of the study was to examine the 1-year cumulative incidence of episodic neck pain and to explore its associations with individual risk factors, including a history of previous neck injury. A baseline cross-sectional survey of an adult general population sample made up of all 7669 adults aged 18-75 years, registered with two family practices in South Manchester, United Kingdom, identified the study population of adults with no current neck pain. This study population was surveyed again 12 months later to identify all those who had experienced neck pain during the follow-up period. At follow-up, cumulative 1-year episode incidence of neck pain was estimated at 17.9% (95% confidence interval 16.0-19.7%). Incidence was independent of age, but was more common in women. A history of previous neck injury at baseline was a significant risk factor for subsequent neck pain in the follow-up year (risk ratio 1.7, 95% confidence interval 1.2-2.5), independent of gender and psychological status. Other independent baseline risk factors for subsequent neck pain included number of children, poor self-assessed health, poor psychological status and a past history of low back pain. We have carried out a prospective study in a general population sample and demonstrated that established risk factors for chronic pain predict future episodes of neck pain, and shown that in addition a history of neck injury is an independent and distinct risk factor. This finding may have major public health and medicolegal implications.

This study outlines the design and validation of a new self-administered instrument for assessing foot pain and disability. The 19-item questionnaire was tested on 45 rheumatology patients, 33 patients who had attended their general practitioner with a foot-related problem and 1000 responders to a population survey of foot disorders. Levels of reported disability were found to be greatest for rheumatology patients and least for community subjects. In addition, the instrument was able to detect differences in disability levels reported by community subjects who did and did not consult with a health care professional and those who did and did not have a history of past and current foot pain. A good level of agreement was found when items on the questionnaire were compared with similar items on the ambulation sub-scale of the Functional Limitation Profile questionnaire. A Cronbach's alpha value of 0.99 and item-total correlation values between 0.25 and 0.62 confirmed the internal consistency of the instrument. Finally the results of a principal components analysis identified three constructs that reflected disabilities that are associated with foot pain: functional limitation, pain intensity and personal appearance. The design of the foot disability questionnaire makes it a suitable instrument for assessing the impact of painful foot conditions in both community and clinical populations.

Although pain is experienced at all ages, there is uncertainty about the pattern of its occurrence in older people. We have investigated the prevalence of three aspects of self-reported pain-occurrence of any recent pain, number and location of pain sites, and interference with daily life-to determine their association with age in older people. A cross-sectional postal survey of all adults aged 50 years and over registered with three general practices (n = 11230) in North Staffordshire using self-complete questionnaires was conducted. Respondents' gender, age, employment status, socio-economic classification, and general health status were gathered to characterise the population under study. The location of any recent pain (past 4 weeks) was recorded on a full-body manikin and pain interference was based on a single question. Completed questionnaires were received from 7878 respondents (adjusted response of 71.3%). The 4-week prevalence of any pain was 72.4%; similar across 10-year age-groups, and higher in females than males. In those with pain the median number of painful areas (from 44) was 6, and 12.5% of the responding population were classified as having widespread pain, both figures similar across age-groups. Most regional pains showed a decline in prevalence in the older age-groups, the exceptions being the lower limb regions (hip, knee, foot). Pain that interfered with daily activities was reported by 3002 (38.1%) respondents overall. There was a clear age-related rise in this prevalence with age up to and including the oldest group. Within each regional pain subgroup, the proportion of people who also reported pain interference rose with age. Our study has provided evidence that increasing age in the elderly population is not associated with any change in the overall prevalence of pain, although, as previous studies have suggested, the pattern of pain prevalence in different body regions does change with age. More importantly the extent to which pain interferes with everyday life increases incrementally with age up to the oldest age-group in the community-dwelling general population.

Many psychological factors have been suggested to be important obstacles to recovery from low back pain, yet most studies focus on a limited number of factors. We compared a more comprehensive range of 20 factors in predicting outcome in primary care. Consecutive patients consulting 8 general practices were eligible to take part in a prospective cohort study; 1591 provided data at baseline and 810 at 6 months. Clinical outcome was defined using the Roland and Morris Disability Questionnaire (RMDQ). The relative strength of the baseline psychological measures to predict outcome was investigated using adjusted multiple linear regression techniques. The sample was similar to other primary care cohorts (mean age 44 years, 59% women, mean baseline RMDQ 8.6). The 20 factors each accounted for between 0.04% and 33.3% of the variance in baseline RMDQ score. A multivariate model including all 11 scales that were associated with outcome in the univariate analysis accounted for 47.7% of the variance in 6 months RMDQ score; rising to 55.8% following adjustment. Four scales remained significantly associated with outcome in the multivariate model explaining 56.6% of the variance: perceptions of personal control, acute/chronic timeline, illness identify and pain self-efficacy. When all independent factors were included, depression, catastrophising and fear avoidance were no longer significant. Thus, a small number of psychological factors are strongly predictive of outcome in primary care low back pain patients. There is clear redundancy in the measurement of psychological factors. These findings should help to focus targeted interventions for back pain in the future.