Association of prion protein with cognitive functioning in humans

Objectives

Recent animal studies have suggested a key role for cellular prion protein (PrPc) in the pathological consequences of amyloid plaque formation, the hallmark of Alzheimer's disease. This epidemiological study investigated whether serum concentrations of PrPc are associated with cognitive functioning in humans.

Design, Setting, Participants

Cross-sectional study of 1,322 participants from the elderly general population in Germany, aged 65 + years at baseline (2000–2002).

Measurements

Cognitive functioning was assessed by the COGTEL phone interview 5 years after baseline. Serum PrPc was determined by a commercial immunoassay.

Results

In multiple linear regression adjusted for important confounders, subjects in higher PrPc quintiles appeared to have lower cognitive functioning scores than those in the lowest PrPc quintile. Spline regression suggested pronounced non-linearity with an inverse association between PrPc and cognitive functioning levelling off beyond median PrPc. Cognitive subdomain-specific models produced somewhat heterogeneous results.

Conclusion

The findings are suggestive of an independent association of PrPc with cognitive functioning in humans. Confirmatory and longitudinal studies are needed to elucidate the potential of PrPc for applications in early risk stratification for cognitive impairment.     

Observational Study Mortality in Treated Primary Aldosteronism: The German Conn's Registry

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.     

Mobile gait analysis via eSHOEs instrumented shoe insoles: a pilot study for validation against the gold standard GAITRite®

Clinical gait analysis contributes massively to rehabilitation support and improvement of in-patient care. The research project eSHOE aspires to be a useful addition to the rich variety of gait analysis systems. It was designed to fill the gap of affordable, reasonably accurate and highly mobile measurement devices. With the overall goal of enabling individual home-based monitoring and training for people suffering from chronic diseases, affecting the locomotor system. Motion and pressure sensors gather movement data directly on the (users) feet, store them locally and/or transmit them wirelessly to a PC. A combination of pattern recognition and feature extraction algorithms translates the motion data into standard gait parameters. Accuracy of eSHOE were evaluated against the reference system GAITRite in a clinical pilot study. Eleven hip fracture patients (78.4?±?7.7 years) and twelve healthy subjects (40.8?±?9.1 years) were included in these trials. All subjects performed three measurements at a comfortable walking speed over 8 m, including the 6-m long GAITRite mat. Six standard gait parameters were extracted from a total of 347 gait cycles. Agreement was analysed via scatterplots, histograms and Bland–Altman plots. In the patient group, the average differences between eSHOE and GAITRite range from ?0.046 to 0.045?s and in the healthy group from ?0.029 to 0.029?s. Therefore, it can be concluded that eSHOE delivers adequately accurate results. Especially with the prospect as an at home supplement or follow-up to clinical gait analysis and compared to other state of the art wearable motion analysis systems.     

Estimation of the relationship between body mass index and EQ-5D health utilities in individuals with type 2 diabetes: Evidence from the population-based KORA studies

ObjectivesObesity is known to be an important risk factor for type 2 diabetes and its related comorbid conditions; however, its specific impact on generic health-related quality of life (HRQL) is less clear. The objective of this study was to estimate the association between body mass index (BMI) and HRQL in individuals with type 2 diabetes.MethodsThe EQ-5D quality of life questionnaire was administered in a follow-up of 10,385 participants aged 33–94 of the population-based German MONICA/KORA surveys. 1033 participants with type 2 diabetes were identified by self-report combined with validated physician diagnoses. Semiparametric additive regression models were used to estimate the effect of BMI on EQ-5D health utilities adjusted for age, sex, education and comorbidities.ResultsBMI was significantly associated with EQ-5D health utilities even after adjustment for macro- and microvascular complications. The functional relationship between BMI and utilities was nonlinear, reflecting optimal health around 26 kg/m² and significantly decreasing health utilities with increasing levels of overweight and obesity (? 0.09 points between BMI values 26 and 40). Among the diabetic complications, the history of a stroke (? 0.13) and neuropathy (? 0.10) were the strongest predictors of reduced health utility scores.ConclusionsBMI is strongly associated with health utilities in persons with type 2 diabetes. This suggests that lifestyle measures to reduce obesity can markedly improve patients' health-related quality of life and that the negative effect of potential weight gain should be taken into account when determining patient preferences for different type 2 diabetes treatment options.     

Creating clinically relevant knowledge from systematic reviews: the challenges of knowledge translation

RATIONALE AND OBJECTIVE: A research translation strategy for chronic pain was developed that has significant potential to advance the usefulness of systematic reviews (SRs) in clinical practice. METHOD: The strategy used interactive case-based workshops that summarize current evidence on treatments for chronic non-cancer pain. Health technology assessment researchers and clinicians collaborated to translate SR evidence into education aids, but this proved far from straightforward. RESULTS: Sourcing and selecting the SR evidence required maintaining a credible balance between the diametrical concepts of comprehensiveness and efficiency, and relevance and validity. On examination of the collated evidence base, further challenges were encountered in dealing with the lack of consistency among the SRs in the quality of execution, the scales used to rate the quality of the evidence, and the conclusions on common topic areas. Strategies for overcoming these difficulties are discussed. CONCLUSIONS: The key elements for creating clinically relevant knowledge from SRs are: a flexible, consistent and transparent methodology; credible research; involvement of renowned content experts to translate the evidence into clinically meaningful guidance; and an open, trusting relationship among all contributors.     

Herzerkrankungen in der Schwangerschaft

Ohne Zusammenfassung Herausgegeben vom Vorstand der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e.V. Bearbeitet im Auftrag der Kommission für Klinische Kardiologie M. Borggrefe, M. B?hm, J. Brachmann, H.-R. Figulla, G. Hasenfu?, H.M. Hoffmeister, A. Osterspey, K. Rybak, U. Sechtem, S. Silber     

A weak blood group A phenotype caused by a translation-initiator mutation in the ABO gene

BACKGROUND: Weak blood group A and B phenotypes are correlated with ABO glycosyltransferases exhibiting single-amino-acid changes and/or C-terminal modifications. STUDY DESIGN AND METHODS: A healthy donor diagnosed as having weak A antigen expression and his two children were subjected to extensive ABO typing. HeLa cells were used to transfect ABO expression plasmids. RESULTS: The donor's red blood cells were type A(weak)B and his serum sample contained weakly reactive anti-A(1) antibodies. A single T>C transition identified at the +2 position of the start codon of an ABO*A101 allele predicted the disruption of this methionine codon. In the transfection studies, a significant reduction of A activity was observed on HeLa cells transfected with a plasmid containing the variant ABO*A allele. Coexpression of the respective antithetical ABO*B101 wild-type construct further reduced cell surface A antigen expression. Similar expression results were obtained with ABO constructs in which the Met(1) start codon and five alternative start sites at codons 20, 26, 43, 53, and 69 had successively been interrupted. CONCLUSION: The donor's weak blood group A phenotype most likely resulted from expression of an N-truncated A transferase triggered by alternative translation start sites in the transmembrane domain or stem region.     

White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV?; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV? groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV? group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.