Echocardiography in the diagnosis left ventricular noncompaction

Echocardiography is the method of choice to establish a diagnosis and determine a treatment plan for patients with noncompaction of ventricular myocardium (NVM). The 2-dimentional echocardiography, 3-dimentional echocardiography, color Doppler echocardiography and contrast-enhanced echocardiography are of critical importance for diagnosis and family screening of NVM

Assessment of explanatory models of mental illness: effects of patient and interviewer characteristics

Background: Explanatory models (EMs) refer to patients’ causal attributions of illness and have been shown to affect treatment preference and outcome. Reliable and valid assessment of EMs may be hindered by interviewer and respondent disparities on certain demographic characteristics, such as ethnicity. The present study examined (a) whether ethnic minority patients reported different EMs to ethnically similar interviewers in comparison with those with a different ethnicity, and (b) whether this effect was related to respondents’ social desirability, the perceived rapport with the interviewer and level of uncertainty toward their EMs. Methods: A total of 55 patients of Turkish and Moroccan origins with mood and anxiety disorders were randomly assigned to ethnically similar or dissimilar interviewers. EMs were assessed, using a semi-structured interview, across 11 different categories of causes. Results: Participants who were interviewed by an ethnically similar interviewer perceived interpersonal, victimization and religious/mystical causes as more important, whereas interviews by ethnically dissimilar interviewers generated higher scores on medical causes. These effects were not mediated by the perceived rapport with the interviewer, and social desirability had a modest impact on the results. Higher uncertainty among participants toward medical and religious/mystical causes seemed to be associated with greater adjustment in the report of these EMs. Conclusion: The findings have significant implications for interviewer selection in epidemiological research and clinical practice

Computational Analysis of Phosphopeptide Binding to the Polo-Box Domain of the Mitotic Kinase PLK1 Using Molecular Dynamics Simulation

The Polo-Like Kinase 1 (PLK1) acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD). The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors

Isolation and Culture of Larval Cells from C. elegans

Cell culture is an essential tool to study cell function. In C. elegans the ability to isolate and culture cells has been limited to embryonically derived cells. However, cells or blastomeres isolated from mixed stage embryos terminally differentiate within 24 hours of culture, thus precluding post-embryonic stage cell culture. We have developed an efficient and technically simple method for large-scale isolation and primary culture of larval-stage cells. We have optimized the treatment to maximize cell number and minimize cell death for each of the four larval stages. We obtained up to 7.8×104 cells per microliter of packed larvae, and up to 97% of adherent cells isolated by this method were viable for at least 16 hours. Cultured larval cells showed stage-specific increases in both cell size and multinuclearity and expressed lineage- and cell type-specific reporters. The majority (81%) of larval cells isolated by our method were muscle cells that exhibited stage-specific phenotypes. L1 muscle cells developed 1 to 2 wide cytoplasmic processes, while L4 muscle cells developed 4 to 14 processes of various thicknesses. L4 muscle cells developed bands of myosin heavy chain A thick filaments at the cell center and spontaneously contracted ex vivo. Neurons constituted less than 10% of the isolated cells and the majority of neurons developed one or more long, microtubule-rich protrusions that terminated in actin-rich growth cones. In addition to cells such as muscle and neuron that are high abundance in vivo, we were also able to isolate M-lineage cells that constitute less than 0.2% of cells in vivo. Our novel method of cell isolation extends C. elegans cell culture to larval developmental stages, and allows use of the wealth of cell culture tools, such as cell sorting, electrophysiology, co-culture, and high-resolution imaging of subcellular dynamics, in investigation of post-embryonic development and physiology

From recommendation to action: psychosocial factors influencing physician intention to use Health Technology Assessment (HTA) recommendations

BACKGROUND: Evaluating the impact of recommendations based upon health technology assessment (HTA) represents a challenge for both HTA agencies and healthcare policy-makers. Using a psychosocial theoretical framework, this study aimed at exploring the factors affecting physician intention to adopt HTA recommendations. The selected recommendations were prioritisation systems for patients on waiting lists for two surgical procedures: hip and knee replacement and cataract surgery. METHODS: Determinants of physician intention to use HTA recommendations for patient prioritisation were assessed by a questionnaire based upon the Theory of Interpersonal Behaviour. A total of 96 physicians from two medical specialties (ophthalmology and orthopaedic surgery) responded to the questionnaire (response rate 44.2%). A multiple analysis of variance (MANOVA) was performed to assess differences between medical specialties on the set of theoretical variables. Given the main effect difference between specialties, two regression models were tested separately to assess the psychosocial determinants of physician intention to use HTA recommendations for the prioritisation of patients on waiting lists for surgical procedures. RESULTS: Factors influencing physician intention to use HTA recommendations differ between groups of specialists. Intention to use the prioritisation system for patients on waiting lists for cataract surgery among ophthalmologists was related to attitude towards the behaviour, social norms, as well as personal normative beliefs. Intention to use HTA recommendations for patient prioritisation for hip and knee replacement among orthopaedic surgeons was explained by: perception of conditions that facilitated the realisation of the behaviour, personal normative beliefs, and habit of using HTA recommendations in clinical work. CONCLUSION: This study offers a model to assess factors influencing the intention to adopt recommendations from health technology assessment into professional practice. Results identify determinant factors that should be considered in the elaboration of strategies to support the implementation of evidence-based practice, with respect to emerging health technologies and modalities of practice. However, it is important to emphasise that behavioural determinants of evidence-based practice vary according to the specific technology considered. Evidence-based implementation of HTA recommendations, as well as other evidence-based practices, should build on a theoretical understanding of the complex forces that shape the practice of healthcare professionals

Elevated Levels of the Polo Kinase Cdc5 Override the Mec1/ATR Checkpoint in Budding Yeast by Acting at Different Steps of the Signaling Pathway

Checkpoints are surveillance mechanisms that constitute a barrier to oncogenesis by preserving genome integrity. Loss of checkpoint function is an early event in tumorigenesis. Polo kinases (Plks) are fundamental regulators of cell cycle progression in all eukaryotes and are frequently overexpressed in tumors. Through their polo box domain, Plks target multiple substrates previously phosphorylated by CDKs and MAPKs. In response to DNA damage, Plks are temporally inhibited in order to maintain the checkpoint-dependent cell cycle block while their activity is required to silence the checkpoint response and resume cell cycle progression. Here, we report that, in budding yeast, overproduction of the Cdc5 polo kinase overrides the checkpoint signaling induced by double strand DNA breaks (DSBs), preventing the phosphorylation of several Mec1/ATR targets, including Ddc2/ATRIP, the checkpoint mediator Rad9, and the transducer kinase Rad53/CHK2. We also show that high levels of Cdc5 slow down DSB processing in a Rad9-dependent manner, but do not prevent the binding of checkpoint factors to a single DSB. Finally, we provide evidence that Sae2, the functional ortholog of human CtIP, which regulates DSB processing and inhibits checkpoint signaling, is regulated by Cdc5. We propose that Cdc5 interferes with the checkpoint response to DSBs acting at multiple levels in the signal transduction pathway and at an early step required to resect DSB ends

Cdc7p-Dbf4p Regulates Mitotic Exit by Inhibiting Polo Kinase

Cdc7p-Dbf4p is a conserved protein kinase required for the initiation of DNA replication. The Dbf4p regulatory subunit binds Cdc7p and is essential for Cdc7p kinase activation, however, the N-terminal third of Dbf4p is dispensable for its essential replication activities. Here, we define a short N-terminal Dbf4p region that targets Cdc7p-Dbf4p kinase to Cdc5p, the single Polo kinase in budding yeast that regulates mitotic progression and cytokinesis. Dbf4p mediates an interaction with the Polo substrate-binding domain to inhibit its essential role during mitosis. Although Dbf4p does not inhibit Polo kinase activity, it nonetheless inhibits Polo-mediated activation of the mitotic exit network (MEN), presumably by altering Polo substrate targeting. In addition, although dbf4 mutants defective for interaction with Polo transit S-phase normally, they aberrantly segregate chromosomes following nuclear misorientation. Therefore, Cdc7p-Dbf4p prevents inappropriate exit from mitosis by inhibiting Polo kinase and functions in the spindle position checkpoint

Anisotropic nanomaterials: structure, growth, assembly, and functions

Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates for devising new applications. In addition, the assembly of ordered one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) arrays of anisotropic nanoparticles brings novel properties into the resulting system, which would be entirely different from the properties of individual nanoparticles. This review presents an overview of current research in the area of anisotropic nanomaterials in general and noble metal nanoparticles in particular. We begin with an introduction to the advancements in this area followed by general aspects of the growth of anisotropic nanoparticles. Then we describe several important synthetic protocols for making anisotropic nanomaterials, followed by a summary of their assemblies, and conclude with major applications

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients