The Role of Extramembranous Cytoplasmic Termini in Assembly and Stability of the Tetrameric K+-Channel KcsA

Membrane-active alcohol 2,2,2-trifluoroethanol has been proven to be an attractive tool in the investigation of the intrinsic stability of integral membrane protein complexes by taking K+-channel KcsA as a suitable and representative ion channel. In the present study, the roles of both cytoplasmic N and C termini in channel assembly and stability of KcsA were determined. The N terminus (1–18 residues) slightly increased tetramer stability via electrostatic interactions in the presence of 30 mol.% acidic phosphatidylglycerol (PG) in phosphatidylcholine lipid bilayer. Furthermore, the N terminus was found to be potentially required for efficient channel (re)assembly. In contrast, truncation of the C terminus (125–160 residues) greatly facilitated channel reversibility from either a partially or a completely unfolded state, and this domain was substantially involved in stabilizing the tetramer in either the presence or absence of PG in lipid bilayer. These studies provide new insights into how extramembranous parts play their crucial roles in the assembly and stability of integral membrane protein complexes

The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial

Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union's Horizon 2020 programme

Barriers to home care for terminally ill Turkish and Moroccan migrants, perceived by GPs and nurses: a survey

BACKGROUND: Previous qualitative research proved that relatives of elderly terminally ill Turkish and Moroccan immigrants experience several barriers to the use of Dutch professional home care. The aim of this study was to explore how general practitioners and home care nurses perceive the home care for terminally ill Turkish and Moroccan migrants and their families in the Netherlands. METHODS: Questionnaires were sent to home care organizations and GPs working in areas where most of these migrants are living. 93 nurses and 78 GPs provided information about their experiences and opinions regarding home care for this group of patients. The data were analyzed by descriptive statistics. RESULTS: GPs refer relatively few patients from these migrant groups to home care. They often find it difficult to assess the needs of these patients and their families. In 40% of the GPs' cases in which terminally ill Turkish and Moroccan migrants were not referred to home care, the GP regretted this afterwards: the patients had not received sufficient qualified care, and their informal carers had often become overburdened. In addition, home care nurses often express dissatisfaction with the home care given to terminally ill Turkish or Moroccan patients, because of communication problems, the patients' lack of knowledge of the disease, or difficulties in making suitable appointments with the patient or with the family. CONCLUSIONS: Nurses and GPs cite chiefly similar factors influencing access to and use of home care as family members did in a previous study. However, according to GPs and nurses, the main barrier to the use of home care concerns communication problems, while relatives cited the preference for family care as the main reason for abstaining from the use of home care. (aut. ref.

Treatments for irritable bowel syndrome: patients' attitudes and acceptability

<p>Abstract</p> <p>Background</p> <p>Irritable Bowel Syndrome, a highly prevalent chronic disorder, places significant burden on the health service and the individual. Symptomatic distress and reduced quality of life are compounded by few efficacious treatments available. As researchers continue to demonstrate the clinical efficacy of alternative therapies, it would be useful to gain a patient-perspective of treatment acceptability and identify patient's attitudes towards those modalities considered not acceptable.</p> <p>Methods</p> <p>Six hundred and forty-five participants identified from an earlier IBS-prevalence study received a postal questionnaire to evaluate preferences and acceptability of nine forms of treatment. Proportions accepting each form of treatment were calculated and thematic analysis of qualitative data undertaken.</p> <p>Results</p> <p>A total of 256 (39.7%) of 645 potential respondents completed the questionnaire (mean age 55.9 years, 73% female). Tablets were most acceptable (84%), followed by lifestyle changes (diet (82%), yoga (77%)). Acupuncture (59%) and suppositories (57%) were less acceptable.</p> <p>When explaining lack of acceptability, patient views fell into four broad categories: dislike treatment modality, do not perceive benefit, general barriers and insufficient knowledge. Scepticism, lack of scientific rationale and fear of CAM were mentioned, although others expressed a dislike of conventional medical treatments. Past experiences, age and health concerns, and need for proof of efficacy were reported.</p> <p>Conclusion</p> <p>Most patients were willing to accept various forms of treatment. However, the reservations expressed by this patient-population must be recognised with particular focus directed towards allaying fears and misconceptions, seeking further evidence base for certain therapies and incorporating physician support and advice.</p

The effects of involving a nurse practitioner in primary care for adult patients with urinary incontinence: The PromoCon study (Promoting Continence)

Contains fulltext : 70765.pdf ( ) (Open Access)BACKGROUND: Urinary incontinence affects approximately 5% (800.000) of the Dutch population. Guidelines recommend pelvic floor muscle/bladder training for most patients. Unfortunately, general practitioners use this training only incidentally, but prescribe incontinence pads. Over 50% of patients get such pads, costing 160 million euros each year. Due to ageing of the population a further increase of expenses is expected. Several national reports recommend to involve nurse specialists to support general practitioners and improve patient care. The main objective of our study is to investigate the effectiveness and cost-effectiveness of involving nurse specialists in primary care for urinary incontinence. This paper describes the study protocol. METHODS/DESIGN: In a pragmatic prospective multi centre two-armed randomized controlled trial in the Netherlands the availability and involvement for the general practitioners of a nurse specialist will be compared with usual care. All consecutive patients consulting their general practitioner within 1 year for urinary incontinence and patients already diagnosed with urinary incontinence are eligible. Included patients will be followed for 12 months.Primary outcome is severity of urinary incontinence (measured with the International Consultation on Incontinence Questionnaire Short Form (ICIQ-UI SF)). Based on ICIQ-UI SF outcome data the number of patients needed to include is 350. For the economic evaluation quality of life and costs will be measured alongside the clinical trial. For the longer term extrapolation of the economic evaluation a Markov modelling approach will be used. DISCUSSION/CONCLUSION: This is, to our knowledge, the first trial on care for patients with urinary incontinence in primary care that includes a full economic evaluation and cost-effectiveness modelling exercise from the societal perspective. If this intervention proves to be effective and cost-effective, implementation of this intervention is considered and anticipated. TRIAL REGISTRATION: Current Controlled Trials ISRCTN62722772

Observational studies of depression in primary care: what do we know?

<p>Abstract</p> <p>Background</p> <p>We undertook a systematic review of observational studies of depression in primary care to determine 1) the nature and scope of the published studies 2) the methodological quality of the studies; 3) the identified recovery and risk factors for persistent depression and 3) the treatment and health service use patterns among patients.</p> <p>Methods</p> <p>Searches were conducted in MEDLINE, CINAHL and PsycINFO using combinations of topic and keywords, and Medical Subject Headings in MEDLINE, Headings in CINAHL and descriptors in PsycINFO. Searches were limited to adult populations and articles published in English during 1985–2006.</p> <p>Results</p> <p>40 articles from 17 observational cohort studies were identified, most were undertaken in the US or Europe. Studies varied widely in aims and methods making it difficult to meaningfully compare the results. Methodological limitations were common including: selection bias of patients and physicians; small sample sizes (range 35–108 patients at baseline and 20–59 patients at follow-up); and short follow-up times limiting the extent to which these studies can be used to inform our understanding of recovery and relapse among primary care patients with depression. Risk factors for the persistence of depression identified in this review were: severity and chronicity of the depressive episode, the presence of suicidal thoughts, antidepressant use, poorer self-reported quality of life, lower self-reported social support, experiencing key life events, lower education level and unemployment.</p> <p>Conclusion</p> <p>Despite the growing interest in depression being managed as a chronic illness, this review identified only 17 observational studies of depression in primary care, most of which have included small sample sizes and been relatively short-term. Future research should be large enough to investigate risk factors for chronicity and relapse, and should be conducted over a longer time frame.</p

Cardiovascular magnetic resonance physics for clinicians: part I

There are many excellent specialised texts and articles that describe the physical principles of cardiovascular magnetic resonance (CMR) techniques. There are also many texts written with the clinician in mind that provide an understandable, more general introduction to the basic physical principles of magnetic resonance (MR) techniques and applications. There are however very few texts or articles that attempt to provide a basic MR physics introduction that is tailored for clinicians using CMR in their daily practice. This is the first of two reviews that are intended to cover the essential aspects of CMR physics in a way that is understandable and relevant to this group. It begins by explaining the basic physical principles of MR, including a description of the main components of an MR imaging system and the three types of magnetic field that they generate. The origin and method of production of the MR signal in biological systems are explained, focusing in particular on the two tissue magnetisation relaxation properties (T1 and T2) that give rise to signal differences from tissues, showing how they can be exploited to generate image contrast for tissue characterisation. The method most commonly used to localise and encode MR signal echoes to form a cross sectional image is described, introducing the concept of k-space and showing how the MR signal data stored within it relates to properties within the reconstructed image. Before describing the CMR acquisition methods in detail, the basic spin echo and gradient pulse sequences are introduced, identifying the key parameters that influence image contrast, including appearances in the presence of flowing blood, resolution and image acquisition time. The main derivatives of these two pulse sequences used for cardiac imaging are then described in more detail. Two of the key requirements for CMR are the need for data acquisition first to be to be synchronised with the subject's ECG and to be fast enough for the subject to be able to hold their breath. Methods of ECG synchronisation using both triggering and retrospective gating approaches, and accelerated data acquisition using turbo or fast spin echo and gradient echo pulse sequences are therefore outlined in some detail. It is shown how double inversion black blood preparation combined with turbo or fast spin echo pulse sequences acquisition is used to achieve high quality anatomical imaging. For functional cardiac imaging using cine gradient echo pulse sequences two derivatives of the gradient echo pulse sequence; spoiled gradient echo and balanced steady state free precession (bSSFP) are compared. In each case key relevant imaging parameters and vendor-specific terms are defined and explained

A theoretical framework to describe communication processes during medical disability assessment interviews

BACKGROUND: Research in different fields of medicine suggests that communication is important in physician-patient encounters and influences satisfaction with these encounters. It is argued that this also applies to the non-curative tasks that physicians perform, such as sickness certification and medical disability assessments. However, there is no conceptualised theoretical framework that can be used to describe intentions with regard to communication behaviour, communication behaviour itself, and satisfaction with communication behaviour in a medical disability assessment context. OBJECTIVE: The objective of this paper is to describe the conceptualization of a model for the communication behaviour of physicians performing medical disability assessments in a social insurance context and of their claimants, in face-to-face encounters during medical disability assessment interviews and the preparation thereof. CONCEPTUALIzATION: The behavioural model, based on the Theory of Planned Behaviour (TPB), is conceptualised for the communication behaviour of social insurance physicians and claimants separately, but also combined during the assessment interview. Other important concepts in the model are the evaluation of communication behaviour (satisfaction), intentions, attitudes, skills, and barriers for communication. CONCLUSION: The conceptualization of the TPB-based behavioural model will help to provide insight into the communication behaviour of social insurance physicians and claimants during disability assessment interviews. After empirical testing of the relationships in the model, it can be used in other studies to obtain more insight into communication behaviour in non-curative medicine, and it could help social insurance physicians to adapt their communication behaviour to their task when performing disability assessment