Sortase-mediated labelling of lipid nanodiscs for cellular tracing

Lipid nanodiscs have broad applications in membrane protein assays, biotechnology and materials science. Chemical modification of the nanodiscs to expand their functional attributes is generally desirable for all of these uses. We present a method for site-selective labelling of the N-terminus of the nanodisc’s membrane scaffold protein (MSP) using the Sortase A protein. Labelling of the MSP was achieved when assembled within the lipid nanodisc architecture, demonstrating that this method can be used as a retrofit approach to modification of preformed nanodiscs before or during application. We label the MSP with a fluorescent fluorescein moiety and use them to image nanodisc uptake into HeLa cells. The Sortase A labelling method could be employed as a general approach to labelling nanodiscs with application-specific functionalities

Musculoskeletal pain is associated with restless legs syndrome in young adults

Background - In recent years, there is considerable evidence of a relationship between the sensorimotor disorder restless legs syndrome (RLS) and pain disorders, including migraine and fibromyalgia. An association between multi-site pain and RLS has been reported in adult women. In the current study, we explored the association between musculoskeletal (MSK) pain and RLS in a large cohort of young adults. Methods - Twenty two year olds (n = 1072), followed since birth of part of the Western Australian Pregnancy Cohort (Raine) Study, provided data on MSK pain (duration, severity, frequency, number of pain sites). RLS was considered present when 4 diagnostic criteria recommended by the International Restless Legs Syndrome Study Group were met (urge to move, dysaesthesia, relief by movement, worsening symptoms during the evening/night) and participants had these symptoms at least 5 times per month. Associations between MSK pain and RLS were analyzed by multivariable logistic regression with bias-corrected bootstrapped confidence intervals, with final models adjusted for sex, psychological distress and sleep quality. Results - The prevalence of RLS was 3.0 % and MSK pain was reported by 37.4 % of the participants. In multivariable logistic regression models, strong associations were found between RLS-diagnosis and long duration (three months or more) of MSK pain (odds ratio 3.6, 95 % confidence interval 1.4–9.2) and reporting three or more pain sites (4.9, 1.6–14.6). Conclusions - Different dimensions of MSK pain were associated with RLS in young adults, suggestive of shared pathophysiological mechanisms. Overlap between these conditions requires more clinical and research attention

A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: A longitudinal cohort study

Background: In this study, we investigated whether an abnormal hypothalamic-pituitary-adrenal (HPA) axis response to psychosocial stress at 18 years of age is associated with musculoskeletal (MS) pain alone and MS pain combined with increased pain sensitivity at 22 years of age. Methods: The study sample included 805 participants from the Western Australian Pregnancy Cohort (Raine) Study who participated in the Trier Social Stress Test (TSST) at age 18 years. Number of pain sites, pain duration, pain intensity and pain frequency were assessed at age 22 to measure severity of MS pain. Cold and pressure pain thresholds were determined at age 22. Group-based trajectory modeling was applied to establish cortisol response patterns based on the TSST. Logistic regression was used to study the association of TSST patterns with MS pain alone and MS pain combined with increased cold or pressure pain sensitivity, adjusted for relevant confounding factors. All analyses were stratified by sex. Results: The mean (standard deviation) age during the TSST was 18.3 (0.3) years, and during MS pain assessment it was 22.2 (0.6). Forty-five percent of the participants were female. Three cortisol response patterns were identified, with cluster 1 (34 % of females, 21 % of males) reflecting hyporesponse, cluster 2 (47 %, 54 %) reflecting intermediate response and cluster 3 (18 %, 24 %) reflecting hyperresponse of the HPA axis. MS pain was reported by 42 % of females and 33 % of males at age 22 years. Compared with females in cluster 2, females in cluster 1 had an increased likelihood of having any MS pain (odds ratio 2.3, 95 % confidence interval 1.0-5.0) and more severe MS pain (2.8, 1.1-6.8) if their cold pain threshold was above the median. In addition, females in cluster 1 had an increased likelihood (3.5, 1.3-9.7) of having more severe MS pain if their pressure pain threshold was below the median. No statistically significant associations were observed in males. Conclusions: This study suggests that a hyporesponsive HPA axis at age 18 years is associated with MS pain at 22 years in young females with increased pain sensitivity

Low back pain in 17 year olds has substantial impact and represents an important public health disorder: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Prevalence of low back pain (LBP) rises rapidly during adolescence, reaching adult levels by the age of 18. It has been suggested that adolescent LBP is benign with minimal impact, despite limited evidence.</p> <p>Methods</p> <p>The aim of this study was to investigate the impact of LBP and the influence of chronicity, gender and presence of other spinal pain comorbidities at age 17. Subjects (n = 1283) were categorised according to experiencing current and chronic LBP, gender and presence of other areas of spinal pain. LBP impact was ascertained via questions regarding seeking professional assistance, using medication, missing school/work, limited normal or recreational physical activity and health related quality of life (HRQOL).</p> <p>Results</p> <p>12.3% of participants reported current but not chronic LBP, while 19.9% reported current chronic LBP. LBP was more commonly reported by females than males. Other spinal pain comorbidities were common in the LBP groups. Impact was greater in subjects with chronic LBP, in females and in those with other spinal pain comorbidities.</p> <p>Conclusion</p> <p>LBP, and particularly chronic LBP, has a significant negative impact at 17 years. It is commonly associated with care seeking, medication use, school absenteeism, and reduced HRQOL. These findings support that adolescent LBP is an important public health issue that requires attention.</p

Characteristics of chronic non-specific musculoskeletal pain in children and adolescents attending a rheumatology outpatients clinic: a cross-sectional study

Background: Chronic non-specific musculoskeletal pain (CNSMSP) may develop in childhood and adolescence, leading to disability and reduced quality of life that continues into adulthood. The purpose of the study was to build a biopsychosocial profile of children and adolescents with CNSMSP. Methods: CNSMSP subjects (n = 30, 18 females, age 7-18) were compared with age matched pain free controls across a number of biopsychosocial domains. Results: In the psychosocial domain CNSMSP subjects had increased levels of anxiety and depression, and had more somatic pain complaints. In the lifestyle domain CNSMSP subjects had lower physical activity levels, but no difference in television or computer use compared to pain free subjects. Physically, CNSMSP subjects tended to sit with a more slumped spinal posture, had reduced back muscle endurance, increased presence of joint hypermobility and poorer gross motor skills. Conclusion: These findings support the notion that CNSMSP is a multidimensional biopsychosocial disorder. Further research is needed to increase understanding of how the psychosocial, lifestyle and physical factors develop and interact in CNSMSP

Work productivity loss in young workers

The Work productivity loss in young workers report examines the prevalence of diagnosed back or neck pain and their contribution towards absenteeism and presenteeism (loss of productive time whilst at work) among young people. Twenty per cent of 23-year-old workers in the study had diagnosed back or neck pain. These workers were estimated to have twice the rate of absenteeism for health reasons and be absent for almost double the number of hours compared to those without back or neck pain. Nationally, the additional annual loss in productivity from absenteeism due to the young people’s back or neck pain is approximately $139 million. The study calculated that the total national loss in annual productivity for all 23-year-olds due to absenteeism and presenteeism (from all causes) is approximately$3.8 billion. The findings are based on an analysis of the Western Australian Pregnancy Cohort (Raine) Study which has tracked over 1000 Western Australian children since pregnancy. Safe Work Australia has worked collaboratively with academics from Curtin University to draft this report

Current practice in management of pelvic girdle pain amongst physiotherapists in Norway and Australia

Pelvic girdle pain (PGP) is frequently managed by physiotherapists. Little is known about current physiotherapy practice and beliefs in the management of PGP disorders. The primary aim of this study was to investigate current practice and beliefs in management of PGP among physiotherapists working in Norway and Australia. A secondary aim was to compare current practice with clinical guidelines. A questionnaire was developed and electronically distributed to physiotherapists in Norway (n = 65) and Australia (n = 77). Treatment and management were determined via responses to 2 case vignettes (during pregnancy, not related to pregnancy), with participants selecting their four primary preferences for treatment and management from a list of 33 possibilities. During pregnancy, ‘education around instability’ and ‘soft tissue treatment’ was selected amongst the most common interventions by physiotherapists in both countries. Norwegian physiotherapists selected ‘pelvic floor exercises’ more frequently, while Australian physiotherapists more commonly selected ‘correcting functional impairments’. In the other case, common responses from both countries were ‘hip strengthening in weight bearing’ and ‘correction of functional impairments’. Norwegian physiotherapists selected ‘general physical exercise’ and ‘general education’ more frequently, while Australian physiotherapists more commonly selected ‘hip strengthening in non-weight bearing’ and ‘muscular relaxation of the abdominal wall/pelvic floor’. Beliefs about PGP were generally positive in both groups while knowledge of and adherences to clinical guidelines were limited. The findings provide direction for future research related to the management and treatment of PGP, and targets for education of physiotherapists working in this area

Correlations between the active straight leg raise, sleep and somatosensory sensitivity during pregnancy with post-partum lumbopelvic pain: An initial exploration

© 2018 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved. For some women, lumbopelvic pain (LPP) developed during pregnancy becomes a continuing post-partum problem. Increased understanding of potential prognostic factors is required. This study investigated whether active straight leg raise (ASLR), sleep dysfunction and pressure pain sensitivity during pregnancy are correlated with LPP intensity and quality, disability, and physical health-related quality of life (HRQoL) post-partum. An exploratory, prospective cohort study design was used. Baseline factors of interest were: (1) ASLR, (2) Pittsburgh Sleep Quality Index, and (3) pressure pain thresholds (PPTs) collected from pregnant women from sites local and distal to the lumbopelvic area. Follow-up data collected 11-18 months post-partum (n=29) were: (1) pain intensity score (numerical rating scale), (2) pain quality (McGill Pain Questionnaire), (3) disability (Pelvic Girdle Questionnaire), and (4) HRQoL (36-item Short Form Health Survey). Correlation analysis was performed. Greater difficulty with an ASLR during pregnancy correlated with lower post-partum physical HRQoL scores (r=-0.563, p=0.002). Likewise, reduced PPTs at the sacrum during pregnancy was correlated with a higher post-partum pain quality score (r=-0.384, p=0.040). In this cohort, findings indicate that poor ASLR performance and localised pressure pain hypersensitivity at the pelvis during pregnancy are correlated with post-partum physical HRQoL and pain quality, respectively. Pain sensitivity may contribute to the prognosis of women with LPP during pregnancy. These explorative findings may be important for designing larger prognostic studies and may assist in directing potential pain management in post-partum LPP

Heightened cold pain and pressure pain sensitivity in young female adults with moderate-to-severe menstrual pain.

This study investigated the association between menstrual pain severity and psychophysical measures of cold and pressure pain sensitivity. A cross-sectional design was used with young women (n = 432) from the Western Australian Pregnancy Cohort (Raine) Study. Menstrual pain severity and oral contraception use was obtained from questionnaires at 20 and 22-year follow-ups. A visual analog scale (VAS; range from 0 [none] to 10 [unbearable]) was used to measure menstrual pain severity at both 20 and 22 years over the 3-year period, with 3 groups created: (1) no pain or mild pain (VAS 0-3), (2) at least moderate pain at a minimum of 1 of the 2 time points (hereafter named "mixed)", and (3) severe pain (VAS 8-10). Cold pain sensitivity (dorsal wrist) and pressure pain sensitivity (lumbar spine, upper trapezius, dorsal wrist, and tibialis anterior) were assessed using standardised quantitative sensory testing protocols. Confounding variables included number of musculoskeletal pain sites, oral contraceptive use, smoking, physical activity, body mass index, psychological distress, and sleep. Severe menstrual pain and mixed menstrual pain were positively associated with heightened cold pain sensitivity (distant from menstrual pain referral site) and pressure pain sensitivity (local to menstrual pain referral site). These associations remained significant after adjusting for potential confounding variables including multisite musculoskeletal pain. Our findings suggest peripheral and central neurophysiological mechanisms contributing to heightened pain sensitivity in young women with moderate and severe menstrual pain. These data highlight the need for innovative management approaches to attenuate the negative impact of severe menstrual pain in young women

Young workers at risk: Absenteeism and presenteeism in raine study 23 year olds

Background As the working population of many countries ages, the reliance on young workers will increase. Government and industry have identified worker productivity as a critical issue to ensure Australia's future. However, currently there is no regularly collected national data set providing ongoing estimates of the productivity of young Australian workers despite the importance of productivity to ergonomics. Aims The aim of this study was to use a representative cohort of young workers to determine levels of productivity loss due to both absenteeism and presenteeism. Methods A cross sectional observational design study was used to gather absenteeism and presenteeism from participants in the Western Australian Pregnancy Cohort (Raine) Study. At around the time of their 23rd birthday, participants were sent a survey which included the World Health Organisation's recommended Health and Productivity Questionnaire (HPQ). Participants report whole and part days absent from work as well as reductions in productivity whilst at work. Results Preliminary data from the first 419 participants who were working full time or part time showed that 60% reported absenteeism in the 28 days preceding the survey due to any reason. The most common duration of absence was one day. The majority of participants (93%) reported some level of presenteeism in the 28 days preceding the survey. The combined mean annualised cost of lost productivity (presenteeism + absenteeism due to any reason) was $15,761.00 per worker. Conclusion Health related productivity loss is a significant issue for young workers and likely to be important to Australia's ongoing productivity. Designing work systems which promote health and reduce the productivity loss associated with ill-health is an important consideration for ergonomics