The hemispheric contrast in cloud microphysical properties constrains aerosol forcing.

The change in planetary albedo due to aerosol-cloud interactions during the industrial era is the leading source of uncertainty in inferring Earth's climate sensitivity to increased greenhouse gases from the historical record. The variable that controls aerosol-cloud interactions in warm clouds is droplet number concentration. Global climate models demonstrate that the present-day hemispheric contrast in cloud droplet number concentration between the pristine Southern Hemisphere and the polluted Northern Hemisphere oceans can be used as a proxy for anthropogenically driven change in cloud droplet number concentration. Remotely sensed estimates constrain this change in droplet number concentration to be between 8 cm-3 and 24 cm-3 By extension, the radiative forcing since 1850 from aerosol-cloud interactions is constrained to be -1.2 W⋅m-2 to -0.6 W⋅m-2 The robustness of this constraint depends upon the assumption that pristine Southern Ocean droplet number concentration is a suitable proxy for preindustrial concentrations. Droplet number concentrations calculated from satellite data over the Southern Ocean are high in austral summer. Near Antarctica, they reach values typical of Northern Hemisphere polluted outflows. These concentrations are found to agree with several in situ datasets. In contrast, climate models show systematic underpredictions of cloud droplet number concentration across the Southern Ocean. Near Antarctica, where precipitation sinks of aerosol are small, the underestimation by climate models is particularly large. This motivates the need for detailed process studies of aerosol production and aerosol-cloud interactions in pristine environments. The hemispheric difference in satellite estimated cloud droplet number concentration implies preindustrial aerosol concentrations were higher than estimated by most models.

A Mokken analysis of the literacy in musculoskeletal problems questionnaire.

BACKGROUND: Limited health literacy is known to impact on medication adherence, hospital readmission and potentially poorer health outcomes. The literature on the health literacy of those with musculoskeletal conditions suggests greater functional limitations and increased pain levels. There are a number of measures of health literacy. One that specifically relates to musculoskeletal complaints is the Literacy in Musculoskeletal Problems (LiMP) questionnaire. The LiMP contains 9 multiple choice items that cover anatomy, musculoskeletal conditions and the diagnosis of musculoskeletal complaints. The aim of the study was to evaluate the dimensionality and internal structure of the LiMP in patients attending for osteopathy care at a student-led clinic, as a potential measure of musculoskeletal health literacy. METHOD: Three hundred and sixty-one (n = 361) new patients attending the Victoria University Osteopathy Clinic completed the LiMP and a demographic and health information questionnaire prior to their initial consultation. Mokken scale analysis, a nonparametric item response theory approach, was used to evaluate the dimensionality and structure of the LiMP in this population, to ascertain whether the questionnaire was measuring a single latent construct - musculoskeletal health literacy. McDonald's omega and Cronbach's alpha were calculated as the reliability estimations. The relationship between the LiMP and a single item screen of health literacy was also undertaken. RESULTS: The 9 items on the LiMP did not form a Mokken scale and the reliability estimations were below an acceptable level (alpha and omega <0.45). LiMP items 5 and 8 were more likely to be answered correctly by those with higher health literacy (p < 0.05), however the effect sizes were small (<0.20). CONCLUSION: Calculation of a total score for the LiMP, as advocated by the original authors, is not supported based on data in the present study. Further research is required to explore the relationship of the LiMP items to demographic and clinical data, and to other broader measures of health literacy. Further research may also develop a health literacy measure that is specific to patients seeking manual therapy care for musculoskeletal complaints.

The DREEM, part 2: psychometric properties in an osteopathic student population.

BACKGROUND: The Dundee Ready Educational Environment Measure (DREEM) is widely used to assess the educational environment in health professional education programs. A number of authors have identified issues with the psychometric properties of the DREEM. Part 1 of this series of papers presented the quantitative data obtained from the DREEM in the context of an Australian osteopathy program. The present study used both classical test theory and item response theory to investigate the DREEM psychometric properties in an osteopathy student population. METHODS: Students in the osteopathy program at Victoria University (Melbourne, Australia) were invited to complete the DREEM and a demographic questionnaire at the end of the 2013 teaching year (October 2013). Data were analysed using both classical test theory (confirmatory factor analysis) and item response theory (Rasch analysis). RESULTS: Confirmatory factor analysis did not demonstrate model fit for the original 5-factor DREEM subscale structure. Rasch analysis failed to identify a unidimensional model fit for the 50-item scale, however model fit was achieved for each of the 5 subscales independently. A 12-item version of the DREEM was developed that demonstrated good fit to the Rasch model, however, there may be an issue with the targeting of this scale given the mean item-person location being greater than 1. CONCLUSIONS: Given that the full 50-item scale is not unidimensional; those using the DREEM should avoid calculating a total score for the scale. The 12-item 'short-form' of the DREEM warrants further investigation as does the subscale structure. To confirm the reliability of the DREEM, as a measure to evaluate the appropriateness of the educational environment of health professionals, further work is required to establish the psychometric properties of the DREEM, with a range of student populations.

Checking nasogastric tube safety in children cared for in the community: a re-examination of the evidence base.

Nasogastric tube feeding is generally considered safe provided a nasogastric aspirate with a pH ≤5.5, which indicates that the end of tube is correctly located in the stomach, can be obtained. When this is not possible, hospital attendance or admission is usually required so that an X-ray can be undertaken to check the tube's position. This practice is based on an interpretation of the evidence that places undue importance on nasogastric aspirate pH testing before every use of a tube that is already in place, with potential negative consequences for children cared for in the community and their families. Following a re-examination of the evidence base, a revised approach is proposed in this article: when a child has a tube in place, provided its position has been confirmed as correct on initial placement using aspirate pH testing, nurses can use checks other than aspirate pH testing, alongside their clinical judgement, to determine whether it is safe and appropriate to use the tube. This proposed revised approach would reduce delayed or missed administration of fluids, feeds and medicines and enable more children to remain at home.

Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

BACKGROUND: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. OBJECTIVE: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. METHODS: The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. RESULTS: Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. CONCLUSIONS: Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

Utilisation of pain counselling in osteopathic practice: secondary analysis of a nationally representative sample of Australian osteopaths.

OBJECTIVES: Advice, reassurance and education are recommended as first line treatments for musculoskeletal pain conditions such as low back pain. Osteopaths are registered primary contact allied health professionals in the Australian healthcare system who primarily manage acute and chronic musculoskeletal pain conditions. This study aimed to investigate the proportion of Australian osteopaths who do and do not utilise advice, reassurance and education (pain counselling) in their clinical practice, and determine the characteristics associated with the frequency of using pain counselling in clinical practice. METHODS: A secondary analysis of practice characteristics from a nationally representative sample of Australian osteopaths was undertaken. Participants completed a 27-item practice characteristics questionnaire between July-December 2016. Bivariate analyses were used to identify significant variables for inclusion in a backward multiple logistic regression model. Adjusted odds ratios (OR) were calculated for significant variables. RESULTS: Responses were received from 991 Australian osteopaths, representing 49% of the profession. Of these 264 (26.64%) indicated often utilising pain counselling, and 727 (73.36%) reported not often utilising pain counselling. Those who utilised pain counselling were more than twice as likely to report research evidence had a high impact on their clinical practice (OR 2.11), and nearly twice as likely to discuss physical activity with their patients (OR 1.84). CONCLUSIONS: Pain counselling is under-utilised by nearly three quarters of the Australian osteopathic profession as a management strategy. Future studies are required to explore the reasons why most in the profession comprised in this sample are infrequently utilising this guideline recommendation. Given the frequency of chronic musculoskeletal pain conditions presenting to Australian osteopaths, strategies appear to be needed to advance the profession via professional development in accessing and using evidence-based care for pain conditions.

PROMIS Neuropathic and Nociceptive Pain Quality in Musculoskeletal Pain Presentations.

OBJECTIVE: Musculoskeletal pain is a significant contributor to the global disease burden. Management of musculoskeletal pain where a neuropathic component is present can be challenging. This study evaluated the internal structure of the Patient-Reported Outcome Measures Information System (PROMIS) pain quality scales, explored the prevalence of neuropathic and nociceptive pain, and identified health demographics and behaviors related to musculoskeletal pain presentations. METHODS: Patients presenting to the Victoria University Osteopathy Clinic (Melbourne, Vic., Australia) were invited to complete a health demographics and behaviors questionnaire, and the PROMIS Neuropathic (NeuroPQ) and Nociceptive (NociPQ) pain quality scales, before their initial consultation. Descriptive, inferential, and correlation statistics were used to evaluate the PROMIS scales, health demographics, and behaviors. Mokken scale analysis was used to evaluate the internal structure and dimensionality of the NeuroPQ and NociPQ scales. RESULTS: Three hundred eighty-three (N=383) patients completed the measures. Mokken scaling suggested the PROMIS scales demonstrated acceptable internal structure and were unidimensional. Over 22% of patients demonstrated cutoff scores above 50, suggesting a substantive neuropathic pain component to their musculoskeletal presentation. Patients who reported cigarette smoking, not being born in Australia or not speaking English at home, demonstrated higher NeuroPQ scores. Females demonstrated significantly higher NociPQ scores than males. Pain intensity demonstrated small to medium correlations with NeuroPQ and NociPQ scores. DISCUSSION: This study provides support for the use of the NeuroPQ and NociPQ scales in musculoskeletal pain patients. Associations with health demographics and behaviors were identified, and patients typically experienced a combination of neuropathic and nociceptive pain.

Regional Features of Long-Term Exposure to PM2.5 Air Quality over Asia under SSP Scenarios Based on CMIP6 Models.

This study investigates changes in fine particulate matter (PM2.5) concentration and air-quality index (AQI) in Asia using nine different Coupled Model Inter-Comparison Project 6 (CMIP6) climate model ensembles from historical and future scenarios under shared socioeconomic pathways (SSPs). The results indicated that the estimated present-day PM2.5 concentrations were comparable to satellite-derived data. Overall, the PM2.5 concentrations of the analyzed regions exceeded the WHO air-quality guidelines, particularly in East Asia and South Asia. In future SSP scenarios that consider the implementation of significant air-quality controls (SSP1-2.6, SSP5-8.5) and medium air-quality controls (SSP2-4.5), the annual PM2.5 levels were predicted to substantially reduce (by 46% to around 66% of the present-day levels) in East Asia, resulting in a significant improvement in the AQI values in the mid-future. Conversely, weak air pollution controls considered in the SSP3-7.0 scenario resulted in poor AQI values in China and India. Moreover, a predicted increase in the percentage of aged populations (>65 years) in these regions, coupled with high AQI values, may increase the risk of premature deaths in the future. This study also examined the regional impact of PM2.5 mitigations on downward shortwave energy and surface air temperature. Our results revealed that, although significant air pollution controls can reduce long-term exposure to PM2.5, it may also contribute to the warming of near- and mid-future climates.

Determinants of health, health behaviours and demographic profile of patients attending an Australian university student-led osteopathy clinic.

Background: Profiles of health professions practice can inform pre-professional education, provide evidence to assist with interprofessional practice, and inform policy development. An understanding of the profile of patients seeking osteopathy care is emerging. Current research suggests that musculoskeletal presentations predominate with approximately one-third of patients presenting with co-morbid diseases. There is little data on these presentations in Australian osteopathy practice. This study aimed to describe the patient demographics, clinical presentations, health behaviours and determinants of health, including health literacy, of those attending for care at an Australian student-led osteopathy clinic. Methods: A convenience sample design was utilised where consecutive patients presenting for their initial consultation were invited to complete a health information questionnaire during 2016-2017. The questionnaire explored a range of health behaviours and the patient's health status. Data from the clinical records were also extracted to establish the presenting complaint, duration of the complaint and pertinent demographics. Descriptive statistics were generated for each variable. Results: Data were available for 1617 patients presenting for their initial consultation. The mean age of patients was 33.7 (±13.1) years with 55% (n = 887) identifying as female. Acute presentations predominated (n = 840, 52%), with presentations affecting the spine being the most common (57.8%). Most patients rated their health status as good to very good (75%). Approximately 7.5% of patients were identified as having low health literacy and 55.9% were currently suffering from one or more co-morbid presentations. Conclusions: The demographic profile and presenting complaints of patients presenting to a student-led osteopathy clinic are largely consistent with other Australian private practice profiles. The current work also identified co-morbid presentations, and positive and negative health behaviours. Osteopaths may play a role in the management of, or referral for, these presentations where health behaviours require change, or management of co-morbid conditions is beyond the scope of practice. The increasing volume of patient profile literature globally suggests that osteopaths can play a substantial role in the management of musculoskeletal complaints. Further, osteopathy may play a role in screening determinants of health, and engage in multidisciplinary care to ensure those patients with co-morbid conditions or adverse health behaviours are managed appropriately.

PROMIS® General Life Satisfaction scale: construct validity in musculoskeletal pain patients.

BACKGROUND: Life satisfaction is part of subjective well-being. Measurement of life satisfaction is undertaken using self-report measures. This study aimed to evaluate the structural validity, concurrent validity, and internal structure of the PROMIS® General Life Satisfaction Scale (GLSS) in a musculoskeletal pain cohort. METHOD: Consecutive new patients attending the Victoria University Osteopathy Clinic (Melbourne, Australia) were invited to complete the GLSS prior to their initial consultation. Structural validity and internal structure were explored using confirmatory factor analysis and Mokken scale analysis. Concurrent validity was evaluated against a single-item measure of life satisfaction. RESULTS: The PROMIS® GLSS comprised a single factor and formed an acceptable Mokken scale in this population. No differential item functioning was observed. A large positive correlation (r = 0.70) was observed between the General Life Satisfaction scale and a single-item measure of life satisfaction. CONCLUSIONS: The PROMIS® General Life Satisfaction scale demonstrated acceptable internal structure and structural validity in a musculoskeletal pain population. Additional research is required to explore concurrent validity and other measurement properties, however initial data suggests the measure could be a feasible screen of life satisfaction for Australian osteopathic patients.

Life satisfaction and musculoskeletal complaints in a population seeking osteopathy care: consecutive sample of 611 patients.

BACKGROUND: Life satisfaction is a component of the subjective well-being construct. Research consistently suggests that life satisfaction is associated with enhanced social benefits and improved health outcomes. However, its relationship to musculoskeletal health outcomes is underexplored. This study evaluates the life satisfaction of a patient population presenting with musculoskeletal complaints, and the relationship of life satisfaction with other health demographics and behaviours. METHOD: The study used a consecutive sampling design. Patients attending the Victoria University Osteopathy Clinic (Melbourne, Australia) were invited to complete the PROMIS® General Life Satisfaction scale (GLSS) along with questions related to health demographics and behaviours. RESULTS: The GLSS T-score was not significantly different for gender, being born outside of Australia, speaking English at home, or complaint chronicity. CONCLUSIONS: Life satisfaction did not appear to be related to a range of health and demographic variables in the current musculoskeletal pain cohort. The PROMIS® General Life Satisfaction scale could prove useful to explore the relationship between life satisfaction and treatment outcomes for musculoskeletal complaints.

U.K. Community Earth System Modeling for CMIP6.

We describe the approach taken to develop the United Kingdom's first community Earth system model, UKESM1. This is a joint effort involving the Met Office and the Natural Environment Research Council (NERC), representing the U.K. academic community. We document our model development procedure and the subsequent U.K. submission to CMIP6, based on a traceable hierarchy of coupled physical and Earth system models. UKESM1 builds on the well-established, world-leading HadGEM models of the physical climate system and incorporates cutting-edge new representations of aerosols, atmospheric chemistry, terrestrial carbon, and nitrogen cycles and an advanced model of ocean biogeochemistry. A high-level metric of overall performance shows that both models, HadGEM3-GC3.1 and UKESM1, perform better than most other CMIP6 models so far submitted for a broad range of variables. We point to much more extensive evaluation performed in other papers in this special issue. The merits of not using any forced climate change simulations within our model development process are discussed. First results from HadGEM3-GC3.1 and UKESM1 include the emergent climate sensitivity (5.5 and 5.4 K, respectively) which is high relative to the current range of CMIP5 models. The role of cloud microphysics and cloud-aerosol interactions in driving the climate sensitivity, and the systematic approach taken to understand this role, is highlighted in other papers in this special issue. We place our findings within the broader modeling landscape indicating how our understanding of key processes driving higher sensitivity in the two U.K. models seems to align with results from a number of other CMIP6 models.

Evaluating Patient's Understanding of Pain Neurophysiology: Rasch Analysis of the Neurophysiology of Pain Questionnaire.

OBJECTIVE: Educating patients about the neurobiologic basis of their pain experience is an important part of managing patients with pain disorders. The aim of this study was to evaluate the measurement properties of the Neurophysiology of Pain Questionnaire (NPQ) in a population seeking osteopathy treatment for both acute and chronic musculoskeletal pain symptoms. MATERIALS AND METHODS: Patients attending the Victoria University Osteopathy Clinic for their initial osteopathy consultation were recruited consecutively. Before their consultation patients were invited to complete a health information questionnaire and the NPQ. The measurement properties of the NPQ were evaluated using Rasch analysis. RESULTS: Two-hundred and ninety-four patients completed the NPQ (female, 51.7%; mean age, 35.5 y). Over two-thirds of these patients presented with a spinal symptoms and 53% of patient presentations were acute. Initial analysis suggested the NPQ responses did not fit the Rasch model. Modifications to the NPQ including removing items and removing person responses, resulted in the development of a 14-item unidimensional version of the NPQ that was free from differential item functioning. DISCUSSION: The study provides further evidence for the validity of the NPQ total score, derived from a population seeking care for an acute or chronic musculoskeletal pain complaint. The total score is interval-level data and can be used to evaluate changes in pain knowledge before, during, and after pain education interventions. Future studies could utilize this revised version of the NPQ in longitudinal designs and also evaluate pain knowledge changes in conjunction with other objective or subjective pain measures.

The Low-Resolution Version of HadGEM3 GC3.1: Development and Evaluation for Global Climate.

A new climate model, HadGEM3 N96ORCA1, is presented that is part of the GC3.1 configuration of HadGEM3. N96ORCA1 has a horizontal resolution of ~135 km in the atmosphere and 1° in the ocean and requires an order of magnitude less computing power than its medium-resolution counterpart, N216ORCA025, while retaining a high degree of performance traceability. Scientific performance is compared to both observations and the N216ORCA025 model. N96ORCA1 reproduces observed climate mean and variability almost as well as N216ORCA025. Patterns of biases are similar across the two models. In the northwest Atlantic, N96ORCA1 shows a cold surface bias of up to 6 K, typical of ocean models of this resolution. The strength of the Atlantic meridional overturning circulation (16 to 17 Sv) matches observations. In the Southern Ocean, a warm surface bias (up to 2 K) is smaller than in N216ORCA025 and linked to improved ocean circulation. Model El Niño/Southern Oscillation and Atlantic Multidecadal Variability are close to observations. Both the cold bias in the Northern Hemisphere (N96ORCA1) and the warm bias in the Southern Hemisphere (N216ORCA025) develop in the first few decades of the simulations. As in many comparable climate models, simulated interhemispheric gradients of top-of-atmosphere radiation are larger than observations suggest, with contributions from both hemispheres. HadGEM3 GC3.1 N96ORCA1 constitutes the physical core of the UK Earth System Model (UKESM1) and will be used extensively in the Coupled Model Intercomparison Project 6 (CMIP6), both as part of the UK Earth System Model and as a stand-alone coupled climate model.

Publisher Correction: Critical Southern Ocean climate model biases traced to atmospheric model cloud errors.

'In the original HTML version of this Article, ref.12 was incorrectly cited in the first sentence of the first paragraph of the Introduction. The correct citation is ref. 2. This has now been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.'

Critical Southern Ocean climate model biases traced to atmospheric model cloud errors.

The Southern Ocean is a pivotal component of the global climate system yet it is poorly represented in climate models, with significant biases in upper-ocean temperatures, clouds and winds. Combining Atmospheric and Coupled Model Inter-comparison Project (AMIP5/CMIP5) simulations, with observations and equilibrium heat budget theory, we show that across the CMIP5 ensemble variations in sea surface temperature biases in the 40-60°S Southern Ocean are primarily caused by AMIP5 atmospheric model net surface flux bias variations, linked to cloud-related short-wave errors. Equilibration of the biases involves local coupled sea surface temperature bias feedbacks onto the surface heat flux components. In combination with wind feedbacks, these biases adversely modify upper-ocean thermal structure. Most AMIP5 atmospheric models that exhibit small net heat flux biases appear to achieve this through compensating errors. We demonstrate that targeted developments to cloud-related parameterisations provide a route to better represent the Southern Ocean in climate models and projections.

Evaluation of New Zealand osteopathy patients experiences of their treatment.

OBJECTIVES: To investigate the experiences of patients seeking osteopathy treatment in New Zealand; and to describe their perceptions of osteopathic treatment. DESIGN: Survey-based research design. SETTING: Private osteopathy practices. MAIN OUTCOME MEASURES: Demographic survey and the Patient Perception Measure-Osteopathy (PPM-O). RESULTS: Twelve osteopaths were recruited as practitioners. Responses from 107 patients were analysed. Approximately 75% of patients reported receiving a 'mostly cranial' treatment approach. The majority of patients (96.2%) indicated that osteopathic treatment helped their condition. The most frequently experienced sensation was 'relaxed'. A positive relationship was observed between the PPM-O and demographic variables. CONCLUSIONS: This is the first study to report on New Zealand osteopathy patient's experience of their treatment. The sensations and emotions experienced are largely consistent with previous Australian research. Predominantly positive perceptions of osteopathic treatment were reported. The current study provides some evidence of the construct validity of the PPM-O in a New Zealand patient population.

Apolipoprotein E delivery by peritoneal implantation of encapsulated recombinant cells improves the hyperlipidaemic profile in apoE-deficient mice.

Plasma apolipoprotein E (apoE) is a 34-kDa polymorphic protein which has atheroprotective actions by clearing remnant lipoproteins and sequestering excess cellular cholesterol. Low or dysfunctional apoE is a risk factor for hyperlipidaemia and atherosclerosis, and for restenosis after angioplasty. Here, in short-term studies designed to establish proof-of-principle, we investigate whether encapsulated recombinant Chinese hamster ovary (CHO) cells can secrete wild-type apoE3 protein in vitro and then determine whether peritoneal implantation of the microcapsules into apoE-deficient (apoE(-/-)) mice reduces their hypercholesterolaemia. Recombinant CHO-E3 cells were encapsulated into either alginate poly-l-lysine or alginate polyethyleneimine/polybrene microspheres. After verifying stability and apoE3 secretion, the beads were then implanted into the peritoneal cavity of apoE(-/-) mice; levels of plasma apoE3, cholesterol and lipoproteins were monitored for up to 14 days post-implantation. Encapsulated CHO-E3 cells continued to secrete apoE3 protein throughout a 60-day study period in vitro, though levels declined after 14 days. This cell-derived apoE3 was biologically active. When conditioned medium from encapsulated CHO-E3 cells was incubated with cultured cells pre-labelled with [(3)H]-cholesterol, efflux of cholesterol was two to four times greater than with normal medium (at 8 h, for example, 7.4+/-0.3% vs. 2.4+/-0.2% of cellular cholesterol; P<0.001). Moreover, when secreted apoE3 was injected intraperitoneally into apoE(-/-) mice, apoE3 was detected in plasma and the hyperlipidaemia improved. Similarly, when alginate polyethyleneimine/polybrene capsules were implanted into the peritoneum of apoE(-/-) mice, apoE3 was secreted into plasma and at 7 days total cholesterol was reduced, while atheroprotective high-density lipoprotein (HDL) increased. In a second study, apoE was detectable in plasma of five mice treated with alginate poly-l-lysine beads, 4 and 7 days post-implantation, though not at day 14. Furthermore, their hypercholesterolaemia was reduced, while HDL was clearly elevated in all mice at days 4 and 7 (from 18.4+/-6.2% of total lipoproteins to 31.1+/-6.8% at 7 days; P<0.001); however, these had rebounded by day 14, possibly due to the emergence of anti-apoE antibodies. We conclude that microencapsulated apoE-secreting cells have the potential to ameliorate the hyperlipidaemia of apoE deficiency, but that the technology must be improved to become a feasible therapeutic to treat atherosclerosis.

Health literacy screening of patients attending a student-led osteopathy clinic: A pilot investigation.

Adequate levels of health literacy (HL) are required for patients to access appropriate health services and develop an understanding of the options for managing their healthcare needs. There is limited literature on HL of patients seeking care for a musculoskeletal complaint. The present study sought to screen the HL of patients presenting to an Australian osteopathy student-led clinic using a single screening question 'Are you confident completing medical forms?'. Less than 10% of patients attending the clinic were considered to have below adequate levels of HL using this question, consistent with other work in Australian populations. Logistic regression analysis identified that the most significant demographic variables associated with lower HL were patients who did not speak English at home, those with lower education levels, and those who were less satisfied with their life. Evaluation of a patients' HL may assist practitioners to improve patient education and management strategies.

Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux.

Although studies in recombinant cells indicate that scavenger receptor class B, type I (SR-BI) can promote cholesterol efflux, investigations in transgenic mice overexpressing or deficient in SR-BI endorse its physiological function as selectively sequestering cholesteryl esters from high-density lipoproteins (HDLs). Less clear is the role of SR-BII, a splice variant of the SR-B gene that differs only in the C-terminal cytoplasmic domain. Here, we identify several putative signalling motifs in the C-terminus of human SR-BII, which are absent from SR-BI, and hypothesize that these motifs interact with signalling molecules to mobilize stored cholesteryl esters and/or promote the efflux of intracellular free cholesterol. 'Pull-down' assays using a panel of tagged SH3 (Src homology 3) domains showed that cytoplasmic SR-BII, but not cytoplasmic SR-BI, bound the SH3 domain of phospholipase C-gamma1; this interaction was not, however, detected under more physiological conditions. Specific anti-peptide antisera identified SR-BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed receptor localization to caveolae, a plasma membrane microdomain that concentrates signal-transducer molecules and acts as a conduit for cholesterol flux between cells and lipoproteins. Consistent with its caveolar localization, expression of human SR-BII in recombinant Chinese hamster ovary cells (CHO-SR-BII) was associated with increased HDL-mediated cholesterol efflux. Nevertheless, when CHO-SR-BII cells were pre-loaded with cholesteryl [(3)H]oleate and incubated with HDL, cholesteryl ester stores were not reduced compared with control cells. We conclude that although human SR-BII is expressed by macrophages, contains cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl esters.