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.     

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.     

Patient satisfaction and suggestions for improvement of remote ICD monitoring

Purpose

The study aim was to evaluate patient acceptance and content with remote follow-up (FU) of their implantable cardioverter defibrillator (ICD) and to estimate patients?? wish for changes in remote follow-up routines.

Methods

Four hundred seventy-four ICD patients at the device follow-up clinic at Rigshospitalet using CareLink? (Medtronic) remote follow-up, who had made ??2 transmissions, received a questionnaire.

Results

Three hundred eighty-five patients (81.2%) answered. Mean time with ICD was 56?±?45?months and mean age was 62?±?13?years; 80% was male. Diagnosis related to ICD implant was: ischemic heart disease in 56% and dilated cardiomyopathy in 21%. Twenty-six percent had primary prophylactic indication. Mean time on remote FU was 16.4?±?6.9?months. Mean time spent on in-clinic FU (two-way transport and FU) was 4?h and 36?min?±?7?h and 50?min, excluding 12 patients from Greenland and Faroe Islands. Ninety-five percent of the patients was very content or content with remote FU compared to in-clinic FU; 3% was less content and 2% was not content. For scheduled transmissions, 21% of the patients wished for a faster reply (sms or e-mail) compared to current practice with a letter. Eighty-four percent preferred more detailed information concerning ICD leads, battery status, and ICD therapies. A total of 96 patients (25%) had performed extra unscheduled remote transmissions: 20 due to shock, 20 due to alarm, 35 due to palpitations, and 18 for other or combined reasons.

Conclusion

Ninety-five percent of the patients were content with the remote FU. Only 25% had unscheduled transmissions and most unscheduled transmissions were for appropriate reasons. Eighty-four percent of the patients wished for a more detailed response and 21% wished for a faster reply after routine transmissions.     

HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients

Background  

HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.     

Exploration of personality factors and their predictive impact on therapy utilization: The externalizing mode of functioning

Abstract

The aim of this study was to identify personality factors predicting psychotherapy utilization on the basis of personality pathology, affect regulation and interpersonal functioning. The authors assessed affectivity (using the Affect Experience and Affect Regulation Q-Sort), interpersonal context (using the Quality of Object Relations Scale), and character pathology (using the Shedler–Westen Assessment Procedure-200). Combination of instruments showed one stable factor predictive for nonengagement in psychotherapy, revealing an externalizing personality dimension, dominated by externalizing defenses, acting out, deficient superego functions, and impairment in reflective functioning and in relating to others. Stability of the predictive power of this personality factor for therapy engagement could be shown, and replication in two other samples confirmed the findings. The results highlight the importance of measuring affect-regulatory mechanisms, and clinical implications for intervention techniques are discussed.     

The use of liquid latex for detecting traces of blood following thermal exposure

International Journal of Legal Medicine - In cases of crimes involving blood, the perpetrators often attempt to remove the traces they have left behind. Setting fire to the crime scene, aside from...     

Hearing protector fit testing with off-shore oil-rig inspectors in Louisiana and Texas

Objective: This field study aimed to assess the noise reduction of hearing protection for individual workers, demonstrate the effectiveness of training on the level of protection achieved, and measure the time required to implement hearing protector fit testing in the workplace. Design: The National Institute for Occupational Safety and Health (NIOSH) conducted field studies in Louisiana and Texas to test the performance of HPD Well-Fit. Study sample: Fit tests were performed on 126 inspectors and engineers working in the offshore oil industry. Results: Workers were fit tested with the goal of achieving a 25-dB PAR. Less than half of the workers were achieving sufficient protection from their hearing protectors prior to NIOSH intervention and training; following re-fitting and re-training, over 85% of the workers achieved sufficient protection. Typical test times were 6–12?minutes. Conclusions: Fit testing of the workers’ earplugs identified those workers who were and were not achieving the desired level of protection. Recommendations for other hearing protection solutions were made for workers who could not achieve the target PAR. The study demonstrates the need for individual hearing protector fit testing and addresses some of the barriers to implementation.     

Domains for activation and inactivation in G protein-coupled receptors – A mutational analysis of constitutive activity of the adenosine A2B receptor

G protein-coupled receptors (GPCRs) are a major drug target and can be activated by a range of stimuli, from photons to proteins. Most, if not all, GPCRs also display a basal level of biological response in the absence of such a stimulus. This level of so-called constitutive activity results from a delicate energy equilibrium that exists between the active and the inactive state of the receptor and is the first determinant in the GPCR activation mechanism. Here we describe new insights in specific regions of the adenosine A_2B receptor that are essential in activation and inactivation. We developed a new screening method using the MMY24 S. Cerevisiae strain by which we were able to screen for constitutively inactive mutants receptors (CIMs). We applied this screening method on a mutagenic library of the adenosine A_2B receptor, where random mutations were introduced in transmembrane domains four and five (TM4 and TM5) linked by extracellular loop 2 (EL2). The screen resulted in the identification of 22 single and double mutant receptors, all showing a decrease in constitutive activity as well as in agonist potency. By comparing these results with a previous screen of the same mutagenic library for constitutively active mutant receptors (CAMs), we discovered specific regions in this G protein-coupled receptor involved in either inactivation or activation or both. The results suggest the activation mechanism of GPCRs to be much less restricted to sites of high conservation or direct interaction with the ligand or G protein and illustrate how dynamic the activation process of GPCRs is.