723 research outputs found

    Using a gamified monitoring app to change adolescents' snack intake : the development of the REWARD app and evaluation design

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    Background: As the snacking pattern of European adolescents is of great concern, effective interventions are necessary. Till now health promotion efforts in children and adolescents have had only limited success in changing adolescents' eating patterns and anthropometrics. Therefore, the present study proposes an innovative approach to influence dietary behaviors in youth based on new insights on effective behavior change strategies and attractive intervention channels to engage adolescents. This article describes the rationale, the development, and evaluation design of the 'Snack Track School' app. The aim of the app is to improve the snacking patterns of Flemish 14- to 16-year olds. Methods: The development of the app was informed by the systematic, stepwise, iterative, and collaborative principles of the Intervention Mapping protocol. A four week mHealth intervention was developed based on the dual-system model with behavioral change strategies targeting both the reflective (i.e., active learning, advance organizers, mere exposure, goal-setting, monitoring, and feedback) and automatic processes (i.e., rewards and positive reinforcement). This intervention will be evaluated via a controlled pre-post design in Flemish schools among 1400 adolescents. Discussion: When this intervention including strategies focused on both the reflective and automatic pathway proves to be effective, it will offer a new scientifically-based vision, guidelines and practical tools for public health and health promotion (i.e., incorporation of learning theories in intervention programs)

    Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements

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    IT-101, a cyclodextrin polymer-based nanoparticle containing camptothecin, is in clinical development for the treatment of cancer. Multiorgan pharmacokinetics and accumulation in tumor tissue of IT-101 is investigated by using PET. IT-101 is modified through the attachment of a 1,4,7,10-tetraazacyclododecane-1,4,7-Tris-acetic acid ligand to bind ^(64)Cu^(2+). This modification does not affect the particle size and minimally affects the surface charge of the resulting nanoparticles. PET data from ^(64)Cu-labeled IT-101 are used to quantify the in vivo biodistribution in mice bearing Neuro2A s.c. tumors. The ^(64)Cu-labeled IT-101 displays a biphasic plasma elimination. Approximately 8% of the injected dose is rapidly cleared as a low-molecular-weight fraction through the kidneys. The remaining material circulates in plasma with a terminal half-life of 13.3 h. Steadily increasing concentrations, up to 11% injected dose per cm^3, are observed in the tumor over 24 h, higher than any other tissue at that time. A 3-compartment model is used to determine vascular permeability and nanoparticle retention in tumors, and is able to accurately represent the experimental data. The calculated tumor vascular permeability indicates that the majority of nanoparticles stay intact in circulation and do not disassemble into individual polymer strands. A key assumption to modeling the tumor dynamics is that there is a “sink” for the nanoparticles within the tumor. Histological measurements using confocal microscopy show that IT-101 localizes within tumor cells and provides the sink in the tumor for the nanoparticles

    A36-dependent actin filament nucleation promotes release of vaccinia virus

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    Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36YdF virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36YdF infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36YdF extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5P189S mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions. © 2013 Horsington et al

    A36-dependent Actin Filament Nucleation Promotes Release of Vaccinia Virus

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    Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36(YdF) virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36(YdF) infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36(YdF) extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5(P189S) mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions.This work was outlined and supported by Project Grant #632785 of the National Health and Medical Research Council of Australia and The Australian Research Council Federation Discovery Project #1096623. CBW was supported by a National Health and Medical Research Council of Australia Senior Research Fellowship #571905. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Lack of trust in maternal support is associated with negative interpretations of ambiguous maternal behavior

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    Attachment theory assumes that children who lack trust in maternal availability for support are more inclined to interpret maternal behavior in congruence with their expectation that mother will remain unavailable for support. To provide the first test of this assumption, early adolescents (9-13 years old) were asked to assess whether ambiguous interactions with mother should be interpreted in a positive or a negative way. In our sample (n = 322), results showed that early adolescents' lack of trust in their mother's availability for support was related to more negative interpretations of maternal behavior. The associations remained significant after controlling for depressive mood. The importance of these findings for our understanding of attachment theory, attachment stability, and clinical practice are discussed

    Isolation and characterization of malaria PfHRP2 specific V-NAR antibody fragments from immunized shark phage display library

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    Background Malaria rapid diagnostic tests (RDTs) represent an important antibody based immunoassay platform. Unfortunately, conventional monoclonal antibodies are subject to degradation shortening shelf lives of RDTs. The variable region of the receptor (VNAR) from shark has a potential as alternative to monoclonal antibodies in RDTs due to high thermal stability. Methods In this study, new binders derived from shark VNAR domains library were investigated. Following immunization of a wobbegong shark (Orectolobus ornatus) with three recombinant malaria biomarker proteins (PfHRP2, PfpLDH and Pvaldolase), a single domain antibody (sdAb) library was constructed from splenocytes. Target-specific VNAR phage were isolated by panning. One specific clone was selected for expression in Escherichia coli expression system, and study of binding reactivity undertaken. Results The primary VNAR domain library possessed a titre of 1.16 × 106&nbsp;pfu/mL. DNA sequence analysis showed 82.5% of isolated fragments appearing to contain an in-frame sequence. After multiple rounds of biopanning, a highly dominant clone specific to PfHRP2 was identified and selected for protein production in an E. coli expression system. Biological characterization showed the recombinant protein expressed in periplasmic has better detection sensitivity than that of cytoplasmic proteins. Assays of binding activity indicated that its reactivity was inferior to the positive control mAb C1–13. Conclusions Target-specific bacteriophage VNARs were successfully isolated after a series of immunization, demonstrating that phage display technology is a useful tool for selection of antigen binders. Generation of new binding reagents such as VNAR antibodies that specifically recognize the malaria biomarkers represents an appealing approach to improve the performance of RDTs.</p

    Getting to the Heart of Emotion Regulation in Youth: The Role of Interoceptive Sensitivity, Heart Rate Variability, and Parental Psychopathology

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    Emotion regulation and associated autonomic activation develop throughout childhood and adolescence under the influence of the family environment. Specifically, physiological indicators of autonomic nervous system activity such as interoceptive sensitivity and vagally mediated heart rate variability (HRV) can inform on emotion regulation. Although the effect of parental emotion socialization on emotion regulation appears to be influenced by autonomic processes, research on physiological regulation and the influence of parental factors remains scarce. This study investigated the relationship between self-reported habitual emotion regulation strategies and HRV at rest as well as interoceptive sensitivity in forty-six youngsters (27 female; age: M = 13.00, SD = 2.13). Secondly, the association between these autonomic correlates and parental psychopathology was also studied. Whereas better interoceptive sensitivity was related to reduced maladaptive emotion regulation, specifically rumination, high HRV was related to more use of external emotion regulation strategies (i.e., support seeking). In addition, increased HRV and decreased interoceptive sensitivity were associated with maternal internalizing and there was evidence for a possible mediation effect of HRV in the relationship between maternal internalizing and child external emotion regulation. This study elucidates the link between cognitive emotion regulation strategies and underlying physiological regulation in adolescents but also indicates a putative influence of maternal internalizing symptoms on emotion regulation in their offspring
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