Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Cross-cultural adaptation of research instruments: language, setting, time and statistical considerations

<p>Abstract</p> <p>Background</p> <p>Research questionnaires are not always translated appropriately before they are used in new temporal, cultural or linguistic settings. The results based on such instruments may therefore not accurately reflect what they are supposed to measure. This paper aims to illustrate the process and required steps involved in the cross-cultural adaptation of a research instrument using the adaptation process of an attitudinal instrument as an example.</p> <p>Methods</p> <p>A questionnaire was needed for the implementation of a study in Norway 2007. There was no appropriate instruments available in Norwegian, thus an Australian-English instrument was cross-culturally adapted.</p> <p>Results</p> <p>The adaptation process included investigation of conceptual and item equivalence. Two forward and two back-translations were synthesized and compared by an expert committee. Thereafter the instrument was pretested and adjusted accordingly. The final questionnaire was administered to opioid maintenance treatment staff (n=140) and harm reduction staff (n=180). The overall response rate was 84%. The original instrument failed confirmatory analysis. Instead a new two-factor scale was identified and found valid in the new setting.</p> <p>Conclusions</p> <p>The failure of the original scale highlights the importance of adapting instruments to current research settings. It also emphasizes the importance of ensuring that concepts within an instrument are equal between the original and target language, time and context. If the described stages in the cross-cultural adaptation process had been omitted, the findings would have been misleading, even if presented with apparent precision. Thus, it is important to consider possible barriers when making a direct comparison between different nations, cultures and times.</p

Using structural equation modeling to detect response shift in performance and health-related quality of life scores of multiple sclerosis patients

To illustrate how structural equation modeling (SEM) can be used for response shift detection with random measurement occasions and health state operationalized as fixed group membership (Study 1) or with fixed measurement occasions and health state operationalized as time-varying covariates (Study 2). In Study 1, we explored seven items of the Performance Scales measuring physical and mental aspects of perceived disability of 771 stable, 629 progressive, and 1,552 relapsing MS patients. Time lags between the three measurements varied and were accounted for by introducing time since diagnosis as an exogenous variable. In Study 2, we considered the SF-12 scales measuring physical and mental components of HRQoL of 1,767 patients. Health state was accounted for by exogenous variables relapse (yes/no) and symptoms (worse/same/better). In Study 1, progressive and relapsing patients reported greater disability than stable patients but little longitudinal change. Some response shift was found with stable and relapsing patients. In Study 2, relapse and symptoms were associated with HRQoL, but no change and only little response shift was found. While small response shifts were found, they had little impact on the evaluation of true change in performance and HRQo

Sociodemographic and Disease Correlates of Body Image Distress among Patients with Systemic Sclerosis

Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (-0.017, p<0.001) and upper-body telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036).This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients

An automated, broad-based, near real-time public health surveillance system using presentations to hospital Emergency Departments in New South Wales, Australia

BACKGROUND: In a climate of concern over bioterrorism threats and emergent diseases, public health authorities are trialling more timely surveillance systems. The 2003 Rugby World Cup (RWC) provided an opportunity to test the viability of a near real-time syndromic surveillance system in metropolitan Sydney, Australia. We describe the development and early results of this largely automated system that used data routinely collected in Emergency Departments (EDs). METHODS: Twelve of 49 EDs in the Sydney metropolitan area automatically transmitted surveillance data from their existing information systems to a central database in near real-time. Information captured for each ED visit included patient demographic details, presenting problem and nursing assessment entered as free-text at triage time, physician-assigned provisional diagnosis codes, and status at departure from the ED. Both diagnoses from the EDs and triage text were used to assign syndrome categories. The text information was automatically classified into one or more of 26 syndrome categories using automated "naïve Bayes" text categorisation techniques. Automated processes were used to analyse both diagnosis and free text-based syndrome data and to produce web-based statistical summaries for daily review. An adjusted cumulative sum (cusum) was used to assess the statistical significance of trends. RESULTS: During the RWC the system did not identify any major public health threats associated with the tournament, mass gatherings or the influx of visitors. This was consistent with evidence from other sources, although two known outbreaks were already in progress before the tournament. Limited baseline in early monitoring prevented the system from automatically identifying these ongoing outbreaks. Data capture was invisible to clinical staff in EDs and did not add to their workload. CONCLUSION: We have demonstrated the feasibility and potential utility of syndromic surveillance using routinely collected data from ED information systems. Key features of our system are its nil impact on clinical staff, and its use of statistical methods to assign syndrome categories based on clinical free text information. The system is ongoing, and has expanded to cover 30 EDs. Results of formal evaluations of both the technical efficiency and the public health impacts of the system will be described subsequently

Spatial Analysis of Land Cover Determinants of Malaria Incidence in the Ashanti Region, Ghana

Malaria belongs to the infectious diseases with the highest morbidity and mortality worldwide. As a vector-borne disease malaria distribution is strongly influenced by environmental factors. The aim of this study was to investigate the association between malaria risk and different land cover classes by using high-resolution multispectral Ikonos images and Poisson regression analyses. The association of malaria incidence with land cover around 12 villages in the Ashanti Region, Ghana, was assessed in 1,988 children <15 years of age. The median malaria incidence was 85.7 per 1,000 inhabitants and year (range 28.4–272.7). Swampy areas and banana/plantain production in the proximity of villages were strong predictors of a high malaria incidence. An increase of 10% of swampy area coverage in the 2 km radius around a village led to a 43% higher incidence (relative risk [RR] = 1.43, p<0.001). Each 10% increase of area with banana/plantain production around a village tripled the risk for malaria (RR = 3.25, p<0.001). An increase in forested area of 10% was associated with a 47% decrease of malaria incidence (RR = 0.53, p = 0.029)

Factor structure of the Hospital Anxiety and Depression Scale in Japanese psychiatric outpatient and student populations

<p>Abstract</p> <p>Background</p> <p>The Hospital Anxiety and Depression Scale (HADS) is a common screening instrument excluding somatic symptoms of depression and anxiety, but previous studies have reported inconsistencies of its factor structure. The construct validity of the Japanese version of the HADS has yet to be reported. To examine the factor structure of the HADS in a Japanese population is needed.</p> <p>Methods</p> <p>Exploratory and confirmatory factor analyses were conducted in the combined data of 408 psychiatric outpatients and 1069 undergraduate students. The data pool was randomly split in half for a cross validation. An exploratory factor analysis was performed on one half of the data, and the fitness of the plausible model was examined in the other half of the data using a confirmatory factor analysis. Simultaneous multi-group analyses between the subgroups (outpatients vs. students, and men vs. women) were subsequently conducted.</p> <p>Results</p> <p>A two-factor model where items 6 and 7 had dual loadings was supported. These factors were interpreted as reflecting anxiety and depression. Item 10 showed low contributions to both of the factors. Simultaneous multi-group analyses indicated a factor pattern stability across the subgroups.</p> <p>Conclusion</p> <p>The Japanese version of HADS indicated good factorial validity in our samples. However, ambiguous wording of item 7 should be clarified in future revisions.</p

The hospitalization burden of influenza just the tip of the iceberg?

Introduction: The codes used to report hospital admissions due to influenza viruses are likely to underestimate the real incidence of influenza-related cases. Methods: In order to estimate this burden we ran a negative binomial model, in which the numbers of weekly admissions for respiratory and cardiovascular diseases were regressed based on influenza syndrome surveillance data (InfluNet), average temperature and seasonality terms. Results: On average over the 2008-2015 period, in addition to 4,407 admissions coded as influenza, we estimated 15,206 additional admissions attributable to influenza. Overall, the total estimated hospital burden attributable to influenza/influenza-like cases is about \u20ac37m per year. Discussion: This estimate should be used for policy making (e.g., vaccine strategies) and operation management choices (e.g., planning and staffing beds during influenza peaks) and encourage the involvement of general practitioners and pediatricians for early symptom control to avoid hospitalization for less severe cases