Energy Distribution in disordered elastic Networks

Disordered networks are found in many natural and artificial materials, from gels or cytoskeletal structures to metallic foams or bones. Here, the energy distribution in this type of networks is modeled, taking into account the orientation of the struts. A correlation between the orientation and the energy per unit volume is found and described as a function of the connectivity in the network and the relative bending stiffness of the struts. If one or both parameters have relatively large values, the struts aligned in the loading direction present the highest values of energy. On the contrary, if these have relatively small values, the highest values of energy can be reached in the struts oriented transversally. This result allows explaining in a simple way remodeling processes in biological materials, for example, the remodeling of trabecular bone and the reorganization in the cytoskeleton. Additionally, the correlation between the orientation, the affinity, and the bending-stretching ratio in the network is discussed

A large-scale proteogenomics study of apicomplexan pathogens-Toxoplasma gondii and Neospora caninum

Proteomics data can supplement genome annotation efforts, for example being used to confirm gene models or correct gene annotation errors. Here, we present a large‐scale proteogenomics study of two important apicomplexan pathogens: Toxoplasma gondii and Neospora caninum. We queried proteomics data against a panel of official and alternate gene models generated directly from RNASeq data, using several newly generated and some previously published MS datasets for this meta‐analysis. We identified a total of 201 996 and 39 953 peptide‐spectrum matches for T. gondii and N. caninum, respectively, at a 1% peptide FDR threshold. This equated to the identification of 30 494 distinct peptide sequences and 2921 proteins (matches to official gene models) for T. gondii, and 8911 peptides/1273 proteins for N. caninum following stringent protein‐level thresholding. We have also identified 289 and 140 loci for T. gondii and N. caninum, respectively, which mapped to RNA‐Seq‐derived gene models used in our analysis and apparently absent from the official annotation (release 10 from EuPathDB) of these species. We present several examples in our study where the RNA‐Seq evidence can help in correction of the current gene model and can help in discovery of potential new genes

Absence of bias against smokers in access to coronary revascularization after cardiac catheterization

Objective. Many consider smoking to be a personal choice for which individuals should be held accountable. We assessed whether there is any evidence of bias against smokers in cardiac care decision-making by determining whether smokers were as likely as non-smokers to undergo revascularization procedures after cardiac catheterization. Design. Prospective cohort study. Subjects and setting. All patients undergoing cardiac catheterization in Alberta, Canada. Main measures. Patients were categorized as current smokers, former smokers, or never smokers, and then compared for their risk-adjusted likelihood of undergoing revascularization procedures (percutaneous coronary intervention or coronary artery bypass grafting) after cardiac catheterization. Results. Among 20406 patients undergoing catheterization, 25.4% were current smokers at the time of catheterization, 36.6% were former smokers, and 38.0% had never smoked. When compared with never smokers (reference group), the hazard ratio for undergoing any revascularization procedure after catheterization was 0.98 (95% CI 0.93-1.03) for current smokers and 0.98 (0.94-1.03) for former smokers. The hazard ratio for undergoing coronary artery bypass grafting was 1.09 (1.00-1.19) for current smokers and 1.00 (0.93-1.08) for former smokers. For percutaneous coronary intervention, the hazard ratios were 0.93 (0.87-0.99) for current smokers and 1.00 (0.94-1.06) for former smokers. Conclusion. Despite potential for discrimination on the basis of smoking status, current and former smokers undergoing cardiac catheterization in Alberta, Canada were as likely to undergo revascularization procedures as catheterization patients who had never smoke

Tourism and the smartphone app: capabilities, emerging practice and scope in the travel domain.

Based on its advanced computing capabilities and ubiquity, the smartphone has rapidly been adopted as a tourism travel tool.With a growing number of users and a wide varietyof applications emerging, the smartphone is fundamentally altering our current use and understanding of the transport network and tourism travel. Based on a review of smartphone apps, this article evaluates the current functionalities used in the domestic tourism travel domain and highlights where the next major developments lie. Then, at a more conceptual level, the article analyses how the smartphone mediates tourism travel and the role it might play in more collaborative and dynamic travel decisions to facilitate sustainable travel. Some emerging research challenges are discussed

Systemic and immune manifestations in myelodysplasia: a multicenter retrospective study

OBJECTIVE: The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002-2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations. METHODS: Forty-six patients with myelodysplasia presenting with systemic and/or immune manifestations were compared in terms of survival with 189 patients with myelodysplasia lacking these features. RESULTS: The clinical picture in these cases consisted of fever (13%), arthralgia or arthritis (13%), and cutaneous manifestations (67%). Four cases of systemic vasculitis have been reported in our series, and they have a worse prognosis. Immune anomalies were recorded in 29% of the cases, and the presence of cryoglobulins was also associated with a worse prognosis. CONCLUSION: A difference in survival between patients with myelodysplastic syndrome with systemic manifestations and patients lacking these manifestations has been observed in the presence of systemic vasculitis and/or cryoglobulins

Uptake of new treatment strategies for deep vein thrombosis: an international audit

Objective. Study of the uptake of new medical technologies provides useful information on the transfer of published evidence into usual practice. We conducted an audit of selected hospitals in three countries (Canada, France, and Switzerland) to identify clinical predictors of low-molecular-weight (LMW) heparin use and outpatient treatment, and to compare the pace of uptake of these new therapeutic approaches across hospitals. Design. Historical review of medical records. Setting and participants. We reviewed the medical records of 3043 patients diagnosed with deep vein thrombosis (DVT) in five Canadian, two French, and two Swiss teaching hospitals from 1994 to 1998. Measures. We explored independent clinical variables associated with LMW heparin use and outpatient treatment, and determined crude and adjusted rates of LMW heparin use and outpatient treatment across hospitals. Results. For the years studied, the overall rates of LMW heparin use and outpatient treatment in the study sample were 34.1 and 15.8%, respectively, with higher rates of use in later years. Many comorbidities were negatively associated with outpatient treatment, and risk-adjusted rates of use of these new approaches varied significantly across hospitals. Conclusion. There has been a relatively rapid uptake of LMW heparins and outpatient treatment for DVT in their early years of availability, but the pace of uptake has varied considerably across hospitals and countrie

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

The role of ectopic human chorionic gonadotropin beta subunit in inducing epithelial mesenchymal transition in human keratinocytes and its possible pathways

Background: The process of epithelial-mesenchymal transition (EMT) involves the trans-differentiation of epithelial cells to mesenchymal cells associated with high plasticity. It usually occurs when the cells acquire migratory and invasive characteristics due to the weakening or the loss of cell-cell adhesion. Human chorionic gonadotropin (hCG), a pregnancy hormone, consists of a common α subunit which is shared by three other hormones, thyroid stimulating hormone, luteinizing hormone and follicular stimulating hormone; and an unique β subunit (hCGβ). Previous studies have demonstrated that hCGβ was expressed by some epithelial origin cancers (1, 2, 3) and therefore it has been postulated as a possible epithelial cancer biomarker. Other studies have linked the presence hCGβ to the aggressive and invasive behavior of certain cancers and their poor prognosis (3, 4). Methods: This study was set out to investigate whether hCGβ plays a role in inducing the EMT and to elucidate the possible pathways. Human keratinocytes (HK) were exposed to spent media collected from hCGβ producing cancer cells (ScaBER cells) for 48 hours before the cells were either fixed for immnuostaining or cells were lysed and protein extracts were collected for western blotting analysis. The expression of epithelial and mesenchymal markers was evaluated by both florescent immunocytochemistry and western blotting techniques. Results: A trend of up-regulation of mesenchymal markers (Vimentin and β-catenin) and down regulation of epithelial marker (E-cadherin) in these treated HK cells was observed. There was 50% increase in cell number which was positively stained by anti-Vimentin antibody whilst 16% of the cells have lost E-cadherin expression (100% to 84%) following 48 hours’ exposure to the hCGβ containing media. These findings were in consistence with the results from HK cells that were exposed to recombinant hCGβ (r-hCGβ). It was also observed that the changes in the expressions of these markers were reduced when a combination of three anti-hCGβ antibodies targeting different hCGβ epitopes was added to the spent media. These results were confirmed by western blotting analysis. Conclusion: The findings suggest that ectopic hCGβ produced by cancer cells might be involved in EMT associated with the migratory and aggressive behavior of such cancers. Furthermore, the up-regulation of β-catenin also suggests its possible role in the Wnt pathway which offers an insight into EMT process at a molecular level. This could be valuable point in developing future novel anti hCGβ therapies for such types of cancers

Modelling and validating three dimensional human normal cervix and cervical cancer tissues in vitro

Objective: The use of three dimensional in vitro systems in cancer research is a promising path for developing effective anticancer therapies. The aim of this study was to engineer a functional 3-D in vitro model of normal and cancerous cervical tissue. Methods: Normal epithelial and immortalized cervical epithelial carcinoma cell lines were used to construct 3-D artificial normal cervical and cervical cancerous tissues. De-epidermised dermis (DED) was used as a scaffold for both models. Morphological analyses were conducted by using haematoxylin and eosin staining and characteristics of the models were studied by analysing the expression of different structural cytokeratins and differential protein marker Mad1 using immunohistochemical technique. Results: Haematoxylin and eosin staining results showed that normal cervical tissue had multi epithelial layers while cancerous cervical tissue showed dysplastic changes. Immunohistochemistry staining results revealed that for normal cervix model cytokeratin 10 was expressed in the upper stratified layer of epithelium while cytokeratin 5 was expressed mainly in the middle and basal layer. Cytokeratin 19 was weakly expressed in a few basal cells. Cervical cancer model showed cytokeratin 19 expression in different epithelial layers and weak or no expression for cytokeratin 5 and cytokeratin 10. Mad1 expression was detected in some suprabasal cells. Conclusions: The 3-D in vitro models showed stratified epithelial layers and expressed the same types and patterns of differentiation marker proteins as seen in corresponding in vivo tissue in either normal cervical or cervical cancerous tissue. Findings imply that they can serve as functional normal and cervical cancer models

Tolvaptan, hyponatremia, and heart failure

Tolvaptan is the first FDA-approved oral V2 receptor antagonist for the treatment of euvolemic and hypervolemic hyponatremia, in patients with conditions associated with free water excess such as heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion. Tolvaptan inhibits the binding of arginine vasopressin to the V2 receptors on the collecting ducts of the kidneys resulting in aquaresis, the electrolytes sparing excretion of water. This article reviews the accumulated experience with tolvaptan and all the major clinical trials that were conducted to study its safety and efficacy and concludes by summarizing clinicians’ views of its current application in clinical practice