Family support and cardiac rehabilitation: A comparative study of the experiences of South Asian and White-European patients and their carer's living in the United Kingdom

Background: Effective lifestyle modification facilitated by cardiac rehabilitation is known to reduce the occurrence of adverse coronary events and mortality. South Asians have poorer outcomes after a myocardial infarction than the general UK population, but little is known about their experiences of family support, cardiac rehabilitation and lifestyle change. Aims: To explore the nature of family support available to a sample of South Asian and White-European cardiac patients and to highlight similarities and differences between these groups with regard to cardiac rehabilitation and lifestyle modification. Methods: Using a qualitative approach, semi-structured interviews (in 1 of 6 languages) were conducted by researchers with; 45 South Asian patients and 37 carers and 20 White-European patients and 17 carers. Interviews were conducted in a home setting, up to eighteen months after discharge from hospital following myocardial infarction, coronary artery bypass surgery or unstable angina. Results: The main themes that emerged related to the provision of advice and information, family support and burden, dietary change and exercise regimes. Conclusions: Several cultural and ethnic differences were identified between patients and their families alongside similarities, irrespective of ethnicity. These may represent generic characteristics of recovery after a cardiac event. Health professionals should develop a cultural repertoire to engage with diversity and difference. Not every difficulty a person encounters as they try to access appropriate service delivery can be attributed to ethnic background. By improving services generally, support for South Asian populations can be improved. The challenge is to know when ethnicity makes a difference and mediates a person's relationship with service support and when it does not. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Gag Mutations Strongly Contribute to HIV-1 Resistance to Protease Inhibitors in Highly Drug-Experienced Patients besides Compensating for Fitness Loss

Human immunodeficiency virus type 1 (HIV-1) resistance to protease inhibitors (PI) results from mutations in the viral protease (PR) that reduce PI binding but also decrease viral replicative capacity (RC). Additional mutations compensating for the RC loss subsequently accumulate within PR and in Gag substrate cleavage sites. We examined the respective contribution of mutations in PR and Gag to PI resistance and RC and their interdependence using a panel of HIV-1 molecular clones carrying different sequences from six patients who had failed multiple lines of treatment. Mutations in Gag strongly and directly contributed to PI resistance besides compensating for fitness loss. This effect was essentially carried by the C-terminal region of Gag (containing NC-SP2-p6) with little or no contribution from MA, CA, and SP1. The effect of Gag on resistance depended on the presence of cleavage site mutations A431V or I437V in NC-SP2-p6 and correlated with processing of the NC/SP2 cleavage site. By contrast, reverting the A431V or I437V mutation in these highly evolved sequences had little effect on RC. Mutations in the NC-SP2-p6 region of Gag can be dually selected as compensatory and as direct PI resistance mutations, with cleavage at the NC-SP2 site behaving as a rate-limiting step in PI resistance. Further compensatory mutations render viral RC independent of the A431V or I437V mutations while their effect on resistance persists

Use of different RT-QuIC substrates for detecting CWD prions in the brain of Norwegian cervids

Chronic wasting disease (CWD) is a highly contagious prion disease affecting captive and free-ranging cervid populations. CWD has been detected in United States, Canada, South Korea and, most recently, in Europe (Norway, Finland and Sweden). Animals with CWD release infectious prions in the environment through saliva, urine and feces sustaining disease spreading between cervids but also potentially to other non-cervids ruminants (e.g. sheep, goats and cattle). In the light of these considerations and due to CWD unknown zoonotic potential, it is of utmost importance to follow specific surveillance programs useful to minimize disease spreading and transmission. The European community has already in place specific surveillance measures, but the traditional diagnostic tests performed on nervous or lymphoid tissues lack sensitivity. We have optimized a Real-Time Quaking-Induced Conversion (RT-QuIC) assay for detecting CWD prions with high sensitivity and specificity to try to overcome this problem. In this work, we show that bank vole prion protein (PrP) is an excellent substrate for RT-QuIC reactions, enabling the detection of trace-amounts of CWD prions, regardless of prion strain and cervid species. Beside supporting the traditional diagnostic tests, this technology could be exploited for detecting prions in peripheral tissues from live animals, possibly even at preclinical stages of the disease

Transmission of Chronic Wasting Disease Identifies a Prion Strain Causing Cachexia and Heart Infection in Hamsters

Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrPSc, prion infection of the central and peripheral neuroendocrine system, and PrPSc deposition in cardiac muscle. There was also prominent PrPSc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the ‘wasting’ or WST strain of hamster CWD

Delays between the onset of symptoms and first rheumatology consultation in patients with rheumatoid arthritis in the UK: an observational study

Objective To investigate delays from symptom onset to rheumatology assessment for patients with a new onset of rheumatoid arthritis (RA) or unclassified arthritis. Methods Newly presenting adults with either RA or unclassified arthritis were recruited from rheumatology clinics. Data on the length of time between symptom onset and first seeing a GP (patient delay), between first seeing a general practitioner (GP) and being referred to a rheumatologist (general practitioner delay) and being seen by a rheumatologist following referral (hospital delay) were captured. Results 822 patients participated (563 female, mean age 55 years). The median time between symptom onset and seeing a rheumatologist was 27.2 weeks (IQR 14.1–66 weeks); only 20% of patients were seen within the first 3 months following symptom onset. The median patient delay was 5.4 weeks (IQR 1.4–26.3 weeks). Patients who purchased over-the-counter medications or used ice/heat packs took longer to seek help than those who did not. In addition, those with a palindromic or an insidious symptom onset delayed for longer than those with a non-palindromic or acute onset. The median general practitioner delay was 6.9 weeks (IQR 2.3–20.3 weeks). Patients made a mean of 4 GP visits before being referred. The median hospital delay was 4.7 weeks (IQR 2.9–7.5 weeks). Conclusion This study identified delays at all levels in the pathway towards assessment by a rheumatologist. However, delays in primary care were particularly long. Patient delay was driven by the nature of symptom onset. Complex multi-faceted interventions to promote rapid help seeking and to facilitate prompt onward referral from primary care should be developed

The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power

We report the development of a 3D OrbiSIMS instrument for label-free biomedical imaging. It combines the high spatial resolution of secondary ion mass spectrometry (SIMS; under 200 nm for inorganic species and under 2 μm for biomolecules) with the high mass-resolving power of an Orbitrap (>240,000 at m/z 200). This allows exogenous and endogenous metabolites to be visualized in 3D with subcellular resolution. We imaged the distribution of neurotransmitters—gamma-aminobutyric acid, dopamine and serotonin—with high spectroscopic confidence in the mouse hippocampus. We also putatively annotated and mapped the subcellular localization of 29 sulfoglycosphingolipids and 45 glycerophospholipids, and we confirmed lipid identities with tandem mass spectrometry. We demonstrated single-cell metabolomic profiling using rat alveolar macrophage cells incubated with different concentrations of the drug amiodarone, and we observed that the upregulation of phospholipid species and cholesterol is correlated with the accumulation of amiodarone

Role of Ligaments in the Knee Joint Kinematic Behavior: Development and Validation of a Finite Element Model

Science Arts & Métiers (SAM)International audienceThe management of knee instability is a complex problem in orthopedic surgery. To comprehensively assess the biomechanical role of the knee joint and to investigate various aspects of knee mechanics, several Finite Element (FE) knee models have been developed. However, (i) the full validation of these models against tibio-femoral and tibio-patellar kinematic data and (ii) the high numerical costs associated with the computation of the biomechanical response of the knee joint are still main issues. Moreover, the contribution on knee mobility of the different ligaments is still unclear. The aim of this study was therefore to develop an FE model with both extensive validation and low computational for the investigation of the role of ligaments in the joint kinematic behavior. To this end, a 3D FE model, consisting of the distal and proximal part of the femur and tibia, respectively, the patella, the quadriceps tendon, the cartilage, and knee ligaments was developed in ANSYS. For the model evaluation, 23 fresh frozen knee joints were tested in flexion/extension using a validated device. The model-predicted response was within or at the limits of the experimental corridors for all translations and rotations of tibia and patella with regard to the femur. A sensitivity analysis was conducted to evaluate the impact of both the stiffness and initial strain of ligaments on the knee kinematic response. Our results showed the high sensitivity of the model to the mechanical parameters of the ligaments