Predictive modelling : parents’ decision making to use online child health information to increase their understanding and/or diagnose or treat their child’s health

Abstract Background The quantum increases in home Internet access and available online health information with limited control over information quality highlight the necessity of exploring decision making processes in accessing and using online information, specifically in relation to children who do not make their health decisions. Objectives To understand the processes explaining parents’ decisions to use online health information for child health care. Methods Parents (N = 391) completed an initial questionnaire assessing the theory of planned behaviour constructs of attitude, subjective norm, and perceived behavioural control, as well as perceived risk, group norm, and additional demographic factors. Two months later, 187 parents completed a follow-up questionnaire assessing their decisions to use online information for their child’s health care, specifically to 1) diagnose and/or treat their child’s suspected medical condition/illness and 2) increase understanding about a diagnosis or treatment recommended by a health professional. Results Hierarchical multiple regression showed that, for both behaviours, attitude, subjective norm, perceived behavioural control, (less) perceived risk, group norm, and (non) medical background were the significant predictors of intention. For parents’ use of online child health information, for both behaviours, intention was the sole significant predictor of behaviour. The findings explain 77% of the variance in parents’ intention to treat/diagnose a child health problem and 74% of the variance in their intentions to increase their understanding about child health concerns. Conclusions Understanding parents’ socio-cognitive processes that guide their use of online information for child health care is important given the increase in Internet usage and the sometimes-questionable quality of health information provided online. Findings highlight parents’ thirst for information; there is an urgent need for health professionals to provide parents with evidence-based child health websites in addition to general population education on how to evaluate the quality of online health information.

IGF2 increases de novo steroidogenesis in prostate cancer cells

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.

Cryo-electron tomography of Marburg Virus particles and their morphogenesis within infected cells

Several major human pathogens, including the filoviruses, paramyxoviruses, and rhabdoviruses, package their single-stranded RNA genomes within helical nucleocapsids, which bud through the plasma membrane of the infected cell to release enveloped virions. The virions are often heterogeneous in shape, which makes it difficult to study their structure and assembly mechanisms. We have applied cryo-electron tomography and sub-tomogram averaging methods to derive structures of Marburg virus, a highly pathogenic filovirus, both after release and during assembly within infected cells. The data demonstrate the potential of cryo-electron tomography methods to derive detailed structural information for intermediate steps in biological pathways within intact cells. We describe the location and arrangement of the viral proteins within the virion. We show that the N-terminal domain of the nucleoprotein contains the minimal assembly determinants for a helical nucleocapsid with variable number of proteins per turn. Lobes protruding from alternate interfaces between each nucleoprotein are formed by the C-terminal domain of the nucleoprotein, together with viral proteins VP24 and VP35. Each nucleoprotein packages six RNA bases. The nucleocapsid interacts in an unusual, flexible "Velcro-like" manner with the viral matrix protein VP40. Determination of the structures of assembly intermediates showed that the nucleocapsid has a defined orientation during transport and budding. Together the data show striking architectural homology between the nucleocapsid helix of rhabdoviruses and filoviruses, but unexpected, fundamental differences in the mechanisms by which the nucleocapsids are then assembled together with matrix proteins and initiate membrane envelopment to release infectious virions, suggesting that the viruses have evolved different solutions to these conserved assembly steps.

Novel keratins identified by quantitative proteomic analysis as the major cytoskeletal proteins of equine (Equus caballus) hoof lamellar tissue

The dermo-epidermal interface that connects the equine distal phalanx to the cornified hoof wall withstands great biomechanical demands, but is also a region where structural failure often ensues as a result of laminitis. The cytoskeleton in this region maintains cell structure and facilitates intercellular adhesion, making it likely to be involved in laminitis pathogenesis, although it is poorly characterized in the equine hoof lamellae. The objective of the present study was to identify and quantify the cytoskeletal proteins present in the epidermal and dermal lamellae of the equine hoof by proteomic techniques. Protein was extracted from the mid-dorsal epidermal and dermal lamellae from the front feet of 5 Standardbred geldings and 1 Thoroughbred stallion. Mass spectrometry-based spectral counting techniques, PAGE, and immunoblotting were used to identify and quantify cytoskeletal proteins, and indirect immunofluorescence was used for cellular localization of K14 and K124 (where K refers to keratin). Proteins identified by spectral counting analysis included 3 actin microfilament proteins; 30 keratin proteins along with vimentin, desmin, peripherin, internexin, and 2 lamin intermediate filament proteins; and 6 tubulin microtubule proteins. Two novel keratins, K42 and K124, were identified as the most abundant cytoskeletal proteins (22.0 ± 3.2% and 23.3 ± 4.2% of cytoskeletal proteins, respectively) in equine hoof lamellae. Immunoreactivity to K14 was localized to the basal cell layer, and that to K124 was localized to basal and suprabasal cells in the secondary epidermal lamellae. Abundant proteins K124, K42, K14, K5, and α1-actin were identified on 1- and 2-dimensional polyacrylamide gels and aligned with the results of previous studies. Results of the present study provide the first comprehensive analysis of cytoskeletal proteins present in the equine lamellae by using mass spectrometry-based techniques for protein quantification and identification.

A description of the Mei2-like protein family; structure, phylogenetic distribution and biological context

The Schizosaccharomyces pombe Mei2 gene encodes an RNA recognition motif (RRM) protein that stimulates meiosis upon binding a specific non-coding RNA and subsequent accumulation in a “mei2-dot” in the nucleus. We present here the first systematic characterization of the family of proteins with characteristic Mei2-like amino acid sequences. Mei2-like proteins are an ancient eukaryotic protein family with three identifiable RRMs. The C-terminal RRM (RRM3) is unique to Mei2-like proteins and is the most highly conserved of the three RRMs. RRM3 also contains conserved sequence elements at its C-terminus not found in other RRM domains. Single copy Mei2-like genes are present in some fungi, in alveolates such as Paramecium and in the early branching eukaryote Entamoeba histolytica, while plants contain small families of Mei2-like genes. While the C-terminal RRM is highly conserved between plants and fungi, indicating conservation of molecular mechanisms, plant Mei2-like genes have changed biological context to regulate various aspects of developmental pattern formation.

Natural articular joints : model of lamellar-rollerbearing lubrication and the nature of the cartilage surface

The influence of pH on interfacial energy and wettability distributed over the phospholipid bilayer surface were studied, and the importance of cartilage hydrophobicity (wettability) on the coefficient of friction (f) was established. It is argued that the wettability of cartilage signifi antly depends on the number of phospholipid bilayers acting as solid lubricant; the hypothesis was proven by conducting friction tests with normal and lipid- depleted cartilage samples. A lamellar-roller-bearing lubrication model was devised involving two mechanisms: (i) lamellar frictionless movement of bilayers, and (ii) roller-bearing lubrication mode through structured synovial fluid, which operates when lamellar spheres, liposomes and macromolecules act like a roller-bearing situated between two cartilage surfaces in effective biological lubrication.

Importance of bearing porosity in engineering and natural lubrication

The multilamellar structure of phospholipids, i.e. the surface amorphous layer (SAL) that covers the natural surface of articular cartilage, and hexagonal boron nitride (h-BN) on the surface of metal porous bearings are two prominent examples of the family of layered materials that possess the ability to deliver lamellar lubrication. This chapter presents the friction study that was conducted on the surfaces of cartilage and the metal porous bearing impregnated with oil (first generation) and with oil + h-BN (second generation). The porosity of cartilage is around 75% and those of metal porous bearings were 15–28 wt%. It is concluded that porosity is a critical factor in facilitating the excellent tribological properties of both articular cartilage and the porous metal bearings studied.

Confronting the conspiracy of silence and denial of difference for late discovery adoptive persons and donor conceived people

This article outlines the impact that a conspiracy of silence and denial of difference has had on some adopted and donor conceived persons who have been lied to or misled about their origins. Factors discussed include deceit - expressed as a central secret which undermines the fabric of a family and through distortion mystifies communication processes; the shock of discovery - often revealed accidentally and the associated sense of betrayal when this occurs; and a series of losses, for example, kinship, medical history, culture and agency which result in having to rebuild personal identity. By providing those affected with a voice, validation and vindication healing can begin. Any feelings of disregard, of betrayal of trust, of anger, frustration, sorrow or loss, need to be regarded as real, expected, and above all, a valid reaction to what has occurred. The author is a 'late discoverer' of her adoption and draws on the information from her doctoral research on the same topic which was completed in 2012.

Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.