Itm2a silencing rescues lamin A mediated inhibition of 3T3-L1 adipocyte differentiation.

Dysregulation of adipose tissue metabolism is associated with multiple metabolic disorders. One such disease, known as Dunnigan-type familial partial lipodystrophy (FPLD2) is characterized by defective fat metabolism and storage. FPLD2 is caused by a specific subset of mutations in the LMNA gene. The mechanisms by which LMNA mutations lead to the adipose specific FPLD2 phenotype have yet to be determined in detail. We used RNA-Seq analysis to assess the effects of wild-type (WT) and mutant (R482W) lamin A on the expression profile of differentiating 3T3-L1 mouse preadipocytes and identified Itm2a as a gene that was upregulated at 36 h post differentiation induction in these cells. In this study we identify Itm2a as a novel modulator of adipogenesis and show that endogenous Itm2a expression is transiently downregulated during induction of 3T3-L1 differentiation. Itm2a overexpression was seen to moderately inhibit differentiation of 3T3-L1 preadipocytes while shRNA mediated knockdown of Itm2a significantly enhanced 3T3-L1 differentiation. Investigation of PPARγ levels indicate that this enhanced adipogenesis is mediated through the stabilization of the PPARγ protein at specific time points during differentiation. Finally, we demonstrate that Itm2a knockdown is sufficient to rescue the inhibitory effects of lamin A WT and R482W mutant overexpression on 3T3-L1 differentiation. This suggests that targeting of Itm2a or its related pathways, including autophagy, may have potential as a therapy for FPLD2.

Chronic Widespread Pain Drawn on a Body Diagram is a Screening Tool for Increased Pain Sensitization, Psycho-Social Load, and Utilization of Pain Management Strategies.

The aim of this study was to investigate the hypothesis that chronic widespread pain, (CWP) drawn by patients on a body diagram, could be used as a screening tool for increased pain sensitization, psycho-social load, and utilization of pain management strategies. The triage questionnaires of 144 adults attending a chronic pain outpatients' clinic were audited and the percentage pain surface area (PPSA) drawn on their body diagrams was calculated using the "rule of nines" (RON) method for burns area assessment. Outcomes were measured using the painDETECT Questionnaire (PD-Q) and other indices and compared using a nonrandomized, case-control method. It was found that significantly more subjects with CWP (defined as a PPSA ≥ 20%) reported high (≥ 19) PD-Q scores (suggesting pain "sensitization" or neuropathic pain) (P = 0.0002), "severe" or "extremely severe" anxiety scores on the Depression, Anxiety and Stress Scale-21 Items Questionnaire (P = 0.0270), ≥ 5 psycho-social stressors (P = 0.0022), ≥ 5 significant life events (P = 0.0098), and used ≥ 7 pain management strategies (PMS) (P < 00001), compared to control subjects with a lower PPSA. A Widespread Pain Index score ≥ 7 (OR = 11.36), PD-Q score ≥ 19 (OR = 4.46) and use of ≥ 7 PMS (OR = 5.49) were independently associated with CWP. This study demonstrates that calculating PPSA on a body diagram (using the RON method) is a valid and convenient "snapshot" screening tool to identify patients with an increased likelihood of pain sensitization, psycho-social load, and utilizing pain management resources.

Spinal pain: current understanding, trends, and the future of care.

This commissioned review paper offers a summary of our current understanding of nonmalignant spinal pain, particularly persistent pain. Spinal pain can be a complex problem, requiring management that addresses both the physical and psychosocial components of the pain experience. We propose a model of care that includes the necessary components of care services that would address the multidimensional nature of spinal pain. Emerging care services that tailor care to the individual person with pain seems to achieve better outcomes and greater consumer satisfaction with care, while most likely containing costs. However, we recommend that any model of care and care framework should be developed on the basis of a multidisciplinary approach to care, with the scaffold being the principles of evidence-based practice. Importantly, we propose that any care services recommended in new models or frameworks be matched with available resources and services - this matching we promote as the fourth principle of evidence-based practice. Ongoing research will be necessary to offer insight into clinical outcomes of complex interventions, while practice-based research would uncover consumer needs and workforce capacity. This kind of research data is essential to inform health care policy and practice.

Implementing evidence-informed policy into practice for health care professionals managing people with low back pain in Australian rural settings: a preliminary prospective single-cohort study.

OBJECTIVE: To provide access to professional development opportunities for health care professionals, especially in rural Australian regions, consistent with recommendations in the Australian National Pain Strategy and state government policy. DESIGN AND SETTING: A preliminary prospective, single-cohort study design, which aligned health policy with evidence-informed clinical practice, evaluated the implementation and effectiveness of an interprofessional, health care provider pain education program (hPEP) for management of nonspecific low back pain (nsLBP) in rural Western Australia. INTERVENTION: The 6.5-hour hPEP intervention was delivered to 60 care providers (caseload nsLBP 19.8% ± 22.5) at four rural WA regions. OUTCOME MEASURES: Outcomes were recorded at baseline and 2 months post-intervention regarding attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale [HC-PAIRS]), Back Pain Beliefs Questionnaire [BBQ]), and self-reported evidence-based clinical practice (knowledge and skills regarding nsLBP, rated on a 5-point Likert scale with 1 = nil and 5 = excellent). RESULTS: hPEP was feasible to implement. At 2 months post-hPEP, responders' (response rate 53%) improved evidence-based beliefs were indicated by HC-PAIRS scores: baseline mean (SD) [43.2 (9.3)]; mean difference (95% CI) [-5.9 (-8.6 to -3.1)]; and BBQ baseline [34.3 (6.8)]; mean difference [2.1 (0.5 to 3.6)]. Positive shifts were observed for all measures of clinical knowledge and skills (P < 0.001) and increased assistance with planning lifestyle changes (P < 0.001), advice on self-management (P = 0.010), and for decreased referrals for spinal imaging (P = 0.03). CONCLUSIONS: This policy-into-practice educational program is feasible to implement in rural Western Australia (WA). While preliminary data are encouraging, a further randomized controlled trial is recommended.

Consumers' experiences of back pain in rural Western Australia: access to information and services, and self-management behaviours.

BACKGROUND: Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP. METHODS: Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals' access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes. RESULTS: Five key themes were identified that affected individuals' experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP. CONCLUSIONS: Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care.

Engaging consumers living in remote areas of Western Australia in the self-management of back pain: a prospective cohort study.

BACKGROUND: In Western Australia (WA), health policy recommends encouraging the use of active self-management strategies as part of the co-care of consumers with persistent low back pain (LBP). As many areas in WA are geographically isolated and health services are limited, implementing this policy into practice is critical if health outcomes for consumers living in geographically-isolated areas are to be improved. METHODS: In this prospective cohort study, 51 consumers (mean (SD) age 62.3 (± 15.1) years) participated in an evidence-based interdisciplinary pain education program (modified Self Training Educative Pain Sessions: mSTEPS) delivered at three geographically isolated WA sites. Self report measures included LBP beliefs and attitudes (Back Pain Beliefs Questionnaire (BBQ); Fear Avoidance Beliefs Questionnaire (FABQ)), use of active and passive self-management strategies, and health literacy, and global perceived impression of usefulness (GPIU) recorded immediately pre-intervention (n = 51), same day post-intervention (BBQ; GPIU, n = 49) and 3 months post-intervention (n = 25). RESULTS: At baseline, consumers demonstrated adequate health literacy and elements of positive health behaviours, reflected by the use of more active than passive strategies in self-managing their persistent LBP. Immediately post-intervention, there was strong evidence for improvement in consumers' general beliefs about LBP as demonstrated by an increase in BBQ scores (baseline [mean (SD): 25.8 (7.6)] to same day post-intervention [28.8 (7.2); P < 0.005], however this improvement was not sustained at 3 months post-intervention. The majority of consumers (86.4%) reported the intervention as very useful [rated on NRS as 7-10]. CONCLUSIONS: To sustain improved consumer beliefs regarding LBP and encourage the adoption of more positive health behaviours, additional reinforcement strategies for consumers living in remote areas where service access and skilled workforce are limited are recommended. This study highlights the need for aligning health services and skilled workforce to improve the delivery of co-care for consumers living in geographically isolated areas.

System plasticity and integrated care: informed consumers guide clinical reorientation and system reorganization.

SETTING: Two Australian public hospital multidisciplinary pain centers (MPCs) situated on opposite sides of the country. OBJECTIVE: Restructuring our services to become patient-centred and patient-driven by enabling entry to our MPCs through an education portal, inclusive of both knowledge and self-management skills, and to then be free to select particular treatment options on the basis of evidence of known efficacy (risk/benefit). DESIGN: Group-based education to inform our patients of the current state of uncertainty that exists in Pain Medicine, both in regard to diagnostic and therapeutic practices. Using an interprofessional team approach, we aimed to present practical and evidence-based advice on techniques of pain self-management and existing traditional medical options. RESULTS: Early, resource efficient, group intervention provides many patients with sufficient information to make informed decisions and enables them to partner us in engaging a whole person approach to their care. We have implemented routine comprehensive audits of clinical services to better inform the planning and provision of health care across health services. CONCLUSIONS: System plasticity is as important to the process of integrated health care as it is to our understanding of the complexity of the lived experience of pain. Better-informed consumers partnered with responsive health professionals drive the proposed paradigm shift in service delivery. The changes better align the needs of consumers with the ability of health care providers to meet them, thus achieving the twin goals of patient empowerment and system efficiency.