Solitary splenic metastasis of squamous lung cancer: a case report

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Telecare motivational interviewing for diabetes patient education and support : a randomised controlled trial based in primary care comparing nurse and peer supporter delivery

Background: There is increasing interest in developing peer-led and 'expert patient'-type interventions, particularly to meet the support and informational needs of those with long term conditions, leading to improved clinical outcomes, and pressure relief on mainstream health services. There is also increasing interest in telephone support, due to its greater accessibility and potential availability than face to face provided support. The evidence base for peer telephone interventions is relatively weak, although such services are widely available as support lines provided by user groups and other charitable services. Methods/Design: In a 3-arm RCT, participants are allocated to either an intervention group with Telecare service provided by a Diabetes Specialist Nurse (DSN), an intervention group with service provided by a peer supporter (also living with diabetes), or a control group receiving routine care only. All supporters underwent a 2-day training in motivational interviewing, empowerment and active listening skills to provide telephone support over a period of up to 6 months to adults with poorly controlled type 2 diabetes who had been recommended a change in diabetes management (i.e. medication and/or lifestyle changes) by their general practitioner (GP). The primary outcome is self-efficacy; secondary outcomes include HbA1c, total and HDL cholesterol, blood pressure, body mass index, and adherence to treatment. 375 participants (125 in each arm) were sought from GP practices across West Midlands, to detect a difference in self-efficacy scores with an effect size of 0.35, 80% power, and 5% significance level. Adults living with type 2 diabetes, with an HbA1c > 8% and not taking insulin were initially eligible. A protocol change 10 months into the recruitment resulted in a change of eligibility by reducing HbA1c to > 7.4%. Several qualitative studies are being conducted alongside the main RCT to describe patient, telecare supporter and practice nurse experience of the trial. Discussion and implications of the research: With its focus on self-management and telephone peer support, the intervention being trialled has the potential to support improved self-efficacy and patient experience, improved clinical outcomes and a reduction in diabetes-related complications

Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

Collaborative denoising autoencoder for high glycated haemoglobin prediction.

A pioneering study is presented demonstrating that the presence of high glycated haemoglobin (HbA1c) levels in a patient’s blood can be reliably predicted from routinely collected clinical data. This paves the way for performing early detection of Type-2 Diabetes Mellitus (T2DM). This will save healthcare providers a major cost associated with the administration and assessment of clinical tests for HbA1c. A novel collaborative denoising autoencoder framework is used to address this challenge. The framework builds an independent denoising autoencoder model for the high and low HbA1c level, which extracts feature representations in the latent space. A baseline model using just three features: patient age together with triglycerides and glucose level achieves 76% F1-score with an SVM classifier. The collaborative denoising autoencoder uses 78 features and can predict HbA1c level with 81% F1-score

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells

<p>Abstract</p> <p>Background</p> <p>In addition to their well-documented ocular therapeutic effects, glucocorticoids (GCs) can cause sight-threatening side-effects including ocular hypertension presumably via morphological and biochemical changes in trabecular meshwork (TM) cells. In the present study, we directly compared the glucocorticoid receptor (GR) potency for dexamethasone (DEX), fluocinolone acetonide (FA) and triamcinolone acetonide (TA), examined the expression of known GRα and GRβ isoforms, and used gene expression microarrays to compare the effects of DEX, FA, and TA on the complete transcriptome in two primary human TM cell lines.</p> <p>Methods</p> <p>GR binding affinity for DEX, FA, and TA was measured by a cell-free competitive radio-labeled GR binding assay. GR-mediated transcriptional activity was assessed using the GeneBLAzer beta-lactamase reporter gene assay. Levels of GRα and GRβ isoforms were assessed by Western blot. Total RNA was extracted from TM 86 and TM 93 cells treated with 1 μM DEX, FA, or TA for 24 hr and used for microarray gene expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by Rosetta Resolver Gene Expression Analysis System.</p> <p>Results</p> <p>The GR binding affinity (IC₅₀) for DEX, FA, and TA was 5.4, 2.0, and 1.5 nM, respectively. These values are similar to the GR transactivation EC₅₀of 3.0, 0.7, and 1.5 nM for DEX, FA, and TA, respectively. All four GRα translational isoforms (A-D) were expressed in TM 86 and TM 93 total cell lysates, however, the C and D isoforms were more highly expressed relative to A and B. All four GRβ isoforms (A-D) were also detected in TM cells, although GRβ-D isoform expression was lower compared to that of the A, B, or C isoforms. Microarray analysis revealed 1,968 and 1,150 genes commonly regulated by DEX, FA, and TA in TM 86 and TM 93, respectively. These genes included RGC32, OCA2, ANGPTL7, MYOC, FKBP5, SAA1 and ZBTB16. In addition, each GC specifically regulated a unique set of genes in both TM cell lines. Using Ingenuity Pathway Analysis (IPA) software, analysis of the data from TM 86 cells showed that DEX significantly regulated transcripts associated with RNA post-transcriptional modifications, whereas FA and TA modulated genes involved in lipid metabolism and cell morphology, respectively. In TM 93 cells, DEX significantly regulated genes implicated in histone methylation, whereas FA and TA altered genes associated with cell cycle and cell adhesion, respectively.</p> <p>Conclusion</p> <p>Human trabecular meshwork cells in culture express all known GRα and GRβ translational isoforms, and GCs with similar potency but subtly different chemical structure are capable of regulating common and unique gene subsets and presumably biologic responses in these cells. These GC structure-dependent effects appear to be TM cell-lineage dependent.</p

DNA Vaccines against Dengue Virus Type 2 Based on Truncate Envelope Protein or Its Domain III

Two DNA vaccines were constructed encoding the ectodomain (domains I, II and III) of the DENV2 envelope protein (pE1D2) or only its domain III (pE2D2), fused to the human tissue plasminogen activator signal peptide (t-PA). The expression and secretion of recombinant proteins was confirmed in vitro in BHK cells transfected with the two plasmids, detected by immunofluorescence or immunoprecipitation of metabolically labeled gene products, using polyclonal and monoclonal antibodies against DENV2. Besides, results reveal that the ectodomain of the E protein can be efficiently expressed in vivo, in a mammalian system, without the prM protein that is hypothesized to act as a chaperonin during dengue infection. Balb/c mice were immunized with the DNA vaccines and challenged with a lethal dose of DENV2. All pE1D2-vaccinated mice survived challenge, while 45% of animals immunized with the pE2D2 died after infection. Furthermore, only 10% of pE1D2-immunized mice presented some clinical signs of infection after challenge, whereas most of animals inoculated with the pE2D2 showed effects of the disease with high morbidity degrees. Levels of neutralizing antibodies were significantly higher in pE1D2-vaccinated mice than in pE2D2-immunized animals, also suggesting that the pE1D2 vaccine was more protective than the pE2D2

Nurse- and peer-led self-management programme for patients with an implantable cardioverter defibrillator; a feasibility study

<p>Abstract</p> <p>Background</p> <p>The prevalence of cardiovascular disease is increasing. Improved treatment options increase survival after an acute myocardial infarction or sudden cardiac arrest, although patients often have difficulty adjusting and regaining control in daily life. In particular, patients who received an implantable cardioverter defibrillator (ICD) experience physical and psychological problems. Interventions to enhance perceived control and acceptance of the device are therefore necessary. This paper describes a small-scale study to explore the feasibility and the possible benefits of a structured nurse- and peer-led self-management programme ('Chronic Disease Self-Management Program' – CDSMP) among ICD patients.</p> <p>Methods</p> <p>Ten male ICD patients (mean age = 65.5 years) participated in a group programme, consisting of six sessions, led by a team consisting of a nurse specialist and a patient with cardiovascular disease. Programme feasibility was evaluated among patients and leaders by measuring performance of the intervention according to protocol, attendance and adherence of the participating ICD patients, and patients' and leaders' opinions about the programme. In addition, before and directly after attending the intervention, programme benefits (e.g. perceived control, symptoms of anxiety and depression, and quality of life) were assessed.</p> <p>Results</p> <p>The programme was conducted largely according to protocol. Eight patients attended at least four sessions, and adherence ranged from good to very good. On average, the patients reported to have benefited very much from the programme, which they gave an overall report mark of 8.4. The leaders considered the programme feasible as well. Furthermore, improvements were identified for general self-efficacy expectancies, symptoms of anxiety, physical functioning, social functioning, role limitations due to physical problems, and pain.</p> <p>Conclusion</p> <p>This study suggests that a self-management programme led by a team consisting of a nurse specialist and a patient with cardiovascular disease seems feasible according to both patients and leaders. The programme may improve general self-efficacy expectancies, symptoms of anxiety, and quality of life (physical functioning, social functioning, role limitations due to physical problems, and pain) as well. Further investigation of the programme's effectiveness among a larger sample of ICD patients or other patient groups with cardiovascular disease, is recommended.</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

Methodological limitations of psychosocial interventions in patients with an implantable cardioverter-defibrillator (ICD) A systematic review

<p>Abstract</p> <p>Background</p> <p>Despite the potentially life-saving benefits of the implantable cardioverter-defibrillator (ICD), a significant group of patients experiences emotional distress after ICD implantation. Different psychosocial interventions have been employed to improve this condition, but previous reviews have suggested that methodological issues may limit the validity of such interventions. Aim: To review the methodology of previously published studies of psychosocial interventions in ICD patients, according to CONSORT statement guidelines for non-pharmacological interventions, and provide recommendations for future research.</p> <p>Methods</p> <p>We electronically searched the PubMed, PsycInfo and Cochrane databases. To be included, studies needed to be published in a peer-reviewed journal between 1980 and 2008, to involve a human population aged 18+ years and to have an experimental design.</p> <p>Results</p> <p>Twelve studies met the eligibility criteria. Samples were generally small. Interventions were very heterogeneous; most studies used cognitive behavioural therapy (CBT) and exercise programs either as unique interventions or as part of a multi-component program. Overall, studies showed a favourable effect on anxiety (6/9) and depression (4/8). CBT appeared to be the most effective intervention. There was no effect on the number of shocks and arrhythmic events, probably because studies were not powered to detect such an effect. Physical functioning improved in the three studies evaluating this outcome. Lack of information about the indication for ICD implantation (primary vs. secondary prevention), limited or no information regarding use of anti-arrhythmic (9/12) and psychotropic (10/12) treatment, lack of assessments of providers' treatment fidelity (12/12) and patients' adherence to the intervention (11/12) were the most common methodological limitations.</p> <p>Conclusions</p> <p>Overall, this review supports preliminary evidence of a positive effect of psychosocial interventions on anxiety and physical functioning in ICD patients. However, these initial findings must be interpreted cautiously because of important methodological limitations. Future studies should be designed as large RCTs, whose design takes into account the specific challenges associated with the evaluation of behavioural interventions.</p