Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial

Background: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. Methods/Design: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. Discussion: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities.Funded by Patient-Centered Outcomes Research Institute (PCORI) Award (AD-1408-19519)

Decline in Health-Related Quality of Life reported by more than half of those waiting for joint replacement surgery: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>In many healthcare systems, people with severe joint disease wait months to years for joint replacement surgery. There are little empirical data on the health consequences of this delay and it is unclear whether people with substantial morbidity at entry to the waiting list continue to deteriorate further while awaiting surgery. This study investigated changes in Health-Related Quality of Life (HRQoL), health status and psychological distress among people waiting for total hip (THR) and knee replacement (TKR) surgery at a major metropolitan Australian public hospital.</p> <p>Methods</p> <p>134 patients completed questionnaires including the Assessment of Quality of Life (AQoL) instrument, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kessler Psychological Distress Scale after entering an orthopaedic waiting list (baseline) and before surgery (preadmission). To quantify potential decline in wellbeing, we calculated the proportion of people experiencing clinically important deterioration using published guidelines and compared HRQoL and psychological distress outcomes with population norms.</p> <p>Results</p> <p>Most participants (69%) waited ≥6 months for surgery (median 286 days, IQR 169-375 days). Despite poor physical and psychological wellbeing at baseline, there was an overall deterioration in HRQoL during the waiting period (mean AQoL change -0.04, 95%CI -0.08 to -0.01), with 53% of participants experiencing decline in HRQoL (≥0.04 AQoL units). HRQoL prior to surgery remained substantially lower than Australian population norms (mean sample AQoL 0.37, 95%CI 0.33 to 0.42 vs mean population AQoL 0.83, 95%CI 0.82 to 0.84). Twenty-five per cent of participants showed decline in health status (≥9.6 WOMAC units) over the waiting period and prevalence of high psychological distress remained high at preadmission (RR 3.5, 95%CI 2.8 to 4.5). Most participants considered their pain (84%), fatigue (76%), quality of life (73%) and confidence in managing their health (55%) had worsened while waiting for surgery.</p> <p>Conclusions</p> <p>Despite substantial initial morbidity, over half of the participants awaiting joint replacement experienced deterioration in HRQoL during the waiting period. These data provide much-needed evidence to guide health professionals and policymakers in the design of care pathways and resource allocation for people who require joint replacement surgery.</p

Particulate air pollution and chronic ischemic heart disease in the eastern United States: a county level ecological study using satellite aerosol data

<p>Abstract</p> <p>Background</p> <p>There are several known factors that cause ischemic heart disease. However, the part played by air pollution still remains something of a mystery. Recent attention has focused on the chronic effect of particulate matter on heart disease. Satellite-derived aerosol optical depth (AOD) was found to be correlated with <it>PM</it>_2.5in the eastern US. The objective of this study was to examine if there is an association between aerosol air pollution as indicated by AOD and chronic ischemic heart disease (CIHD) in the eastern US.</p> <p>Methods</p> <p>An ecological geographic study method was employed. Race and age standardized mortality rate (SMR) of CIHD was computed for each of the 2306 counties for the time period 2003–2004. A mean AOD raster grid for the same period was derived from Moderate Resolution Imaging Spectrometer (MODIS) aerosol data and the average AOD was calculated for each county. A bivariate Moran's I scatter plot, a map of local indicator of spatial association (LISA) clusters, and three regression models (ordinary least square, spatial lag, and spatial error) were used to analyze the relationship between AOD and CIHD SMR.</p> <p>Results</p> <p>The global Moran's I value is 0.2673 (<it>p </it>= 0.001), indicating an overall positive spatial correlation of CIHD SMR and AOD. The entire study area is dominated by spatial clusters of AOD against SMR (high AOD and high SMR in the east, and low AOD and low SMR in the west) (permutations = 999, <it>p </it>= 0.05). Of the three regression models, the spatial error model achieved the best fit (R²= 0.28). The effect of AOD is positive and significant (beta = 0.7774, p = 0.01).</p> <p>Conclusion</p> <p>Aerosol particle pollution has adverse effect on CIHD mortality risk in the eastern US. High risk of CIHD mortality was found in areas with elevated levels of outdoor aerosol air pollution as indicated by satellite derived AOD. The evidence of the association would support targeting of policy interventions on such areas to reduce air pollution levels. Remote sensing AOD data could be used as an alternative health-related indictor of air quality.</p

Protein-Protein Fusion Catalyzed by Sortase A

Chimeric proteins boast widespread use in areas ranging from cell biology to drug delivery. Post-translational protein fusion using the bacterial transpeptidase sortase A provides an attractive alternative when traditional gene fusion fails. We describe use of this enzyme for in vitro protein ligation and report the successful fusion of 10 pairs of protein domains with preserved functionality — demonstrating the robust and facile nature of this reaction

N-Terminal Arginines Modulate Plasma-Membrane Localization of Kv7.1/KCNE1 Channel Complexes

BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks)) is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks) and atrial fibrillation (a human arrhythmia). Structure-function relationship of the KCNE1 N-terminus for I(Ks) modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines) at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks) resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA') were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'). Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks). Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex

A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for longterm protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal ntigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine

Observational analytic studies in multiple sclerosis: controlling bias through study design and conduct. The Australian Multicentre Study of Environment and Immune Function

Rising multiple sclerosis incidence over the last 50 years and geographic patterns of occurrence suggest an environmental role in the causation of this multifactorial disease. Design options for epidemiological studies of environmental causes of multiple sclerosis are limited by the low incidence of the disease, possible diagnostic delay and budgetary constraints. We describe scientific and methodological issues considered in the development of the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study), which seeks, in particular, to better understand the causes of the well-known MS positive latitudinal gradient. A multicentre, case-control design down the eastern seaboard of Australia allows the recruitment of sufficient cases for adequate study power and provides data on environmental exposures that vary by latitude. Cases are persons with an incident first demyelinating event (rather than prevalent multiple sclerosis), sourced from a population base using a two tier notification system. Controls, matched on sex, age (within two years) and region of residence, are recruited from the general population. Biases common in case-control studies, eg, prevalence-incidence bias, admission-rate bias, non-respondent bias, observer bias and recall bias, as well as confounding have been carefully considered in the study design and conduct of the Ausimmune Study

Is there a subjective well-being premium in voluntary sector employment?

Previous studies have found that employment in the voluntary sector offers a so-called ‘job satisfaction premium’: despite lower salaries, voluntary sector employees are more satisfied with their jobs than workers in other sectors. This paper examines whether voluntary sector employees also experience a subjective well-being premium. Using data from the UK Annual Population Survey 2012/2013, we find that voluntary sector employees do have higher levels of subjective well-being but this subjective well-being premium is not evenly distributed between men and women. Men score higher on happiness and life satisfaction. However, women in the voluntary sector have lower levels of life satisfaction compared with their counterparts in the public sector. We discuss the implications of our findings for policy and practice in the voluntary sector in the UK

State owned enterprises as bribe payers: the role of institutional environment

Our paper draws attention to a neglected channel of corruption—the bribe payments by state-owned enterprises (SOEs). This is an important phenomenon as bribe payments by SOEs fruitlessly waste national resources, compromising public welfare and national prosperity. Using a large dataset of 30,249 firms from 50 countries, we show that, in general, SOEs are less likely to pay bribes for achieving organizational objectives owing to their political connectivity. However, in deteriorated institutional environments, SOEs may be subjected to potential managerial rent-seeking behaviors, which disproportionately increase SOE bribe propensity relative to privately owned enterprises. Specifically, our findings highlight the importance of fostering democracy and rule of law, reducing prevalence of corruption and shortening power distance in reducing the incidence of SOE bribery