Utility of Parental Mediation Model on Youth’s Problematic Online Gaming

The Parental Mediation Model PMM) was initially designed to regulate children’s attitudes towards the traditional media. In the present era, because of prevalent online media there is a need for similar regulative measures. Spending long hours on social media and playing online games increase the risks of exposure to the negative outcomes of online gaming. This paper initially applied the PMM developed by European Kids Online to (i) test the reliability and validity of this model and (ii) identify the effectiveness of this model in controlling problematic online gaming (POG). The data were collected from 592 participants comprising 296 parents and 296 students of four foreign universities, aged 16 to 22 years in Kuala Lumpur (Malaysia). The study found that the modified model of the five-factor PMM (Technical mediation, Monitoring mediation, Restrictive mediation, Active Mediation of Internet Safety, and Active mediation of Internet Use) functions as a predictor for mitigating POG. The findings suggest the existence of a positive relation between ‘monitoring’ and ‘restrictive’ mediation strategies and exposure to POG while Active Mediation of Internet Safety and Active mediation of Internet use were insignificant predictors. Results showed a higher utility of ‘technical’ strategies by the parents led to less POG. The findings of this study do not support the literature suggesting active mediation is more effective for reducing youth’s risky behaviour. Instead, parents need to apply more technical mediations with their children and adolescents’ Internet use to minimize the negative effects of online gaming

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Political Self-characterization of U.S. Medical Students

BACKGROUND: There have been no prior studies of the political self-characterization of U.S. physicians-in-training, and little is known about physicians’ political leanings or the critical relationship between medical issues and political orientations of physicians and physicians-in-training. METHODS: All medical students in the class of 2003 at 16 nationally representative U.S. schools were eligible to complete three questionnaire administrations (at freshman orientation, entrance to wards, and senior year). RESULTS: Among these medical students, 5% self-characterized as politically very conservative, 21% conservative, 33% moderate, 31% liberal, and 9% as very liberal.” Being male, white, Protestant, intending to specialize in Surgery or anesthesiology/pathology/radiology, or currently or previously being married significantly (P ≤ .001) increased the likelihood that a student self-identified as very conservative or conservative. Disagreement or strong disagreement with the statements, “I’m glad I chose to become a physician” and “Access to care is a fundamental human right,” were also both associated with being very conservative or conservative. Being more liberal was reported by blacks and Hispanics; those intending to become ob-gyns, psychiatrists, and pediatric subspecialists; and atheists, Jews, and adherents of eastern religions. CONCLUSIONS: U.S. medical students are considerably more likely to be liberal than conservative and are more likely to be liberal than are other young U.S. adults. Future U.S. physicians may be more receptive to liberal messages than conservative ones, and their political orientation may profoundly affect their health system attitudes

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Adherence to 24-Hour Movement Guidelines for the Early Years and associations with social-cognitive development among Australian preschool children

Background: The new Australian 24-Hour Movement Guidelines for the Early Years recommend that, for preschoolers, a healthy 24-h includes: i) ≥180 min of physical activity, including ≥60 min of energetic play, ii) ≤1 h of sedentary screen time, and iii) 10–13 h of good quality sleep. Using an Australian sample, this study reports the proportion of preschool children meeting these guidelines and investigates associations with social-cognitive development. Methods: Data from 248 preschool children (mean age = 4.2 ± 0.6 years, 57% boys) participating in the PATH-ABC study were analyzed. Children completed direct assessments of physical activity (accelerometry) and social cognition (the Test of Emotional Comprehension (TEC) and Theory of Mind (ToM)). Parents reported on children’s screen time and sleep. Children were categorised as meeting/not meeting: i) individual guidelines, ii) combinations of two guidelines, or iii) all three guidelines. Associations were examined using linear regression adjusting for child age, sex, vocabulary, area level socio-economic status and childcare level clustering. Results: High proportions of children met the physical activity (93.1%) and sleep (88.7%) guidelines, whereas fewer met the screen time guideline (17.3%). Overall, 14.9% of children met all three guidelines. Children meeting the sleep guideline performed better on TEC than those who did not (mean difference [MD] = 1.41; 95% confidence interval (CI) = 0.36, 2.47). Children meeting the sleep and physical activity or sleep and screen time guidelines also performed better on TEC (MD = 1.36; 95% CI = 0.31, 2.41) and ToM (MD = 0.25; 95% CI = −0.002, 0.50; p = 0.05), respectively, than those who did not. Meeting all three guidelines was associated with better ToM performance (MD = 0.28; 95% CI = −0.002, 0.48, p = 0.05), while meeting a larger number of guidelines was associated with better TEC (3 or 2 vs. 1/none, p < 0.02) and ToM performance (3 vs. 2, p = 0.03). Conclusions: Strategies to promote adherence to the 24-Hour Movement Behaviour Guidelines for the Early Years among preschool children are warranted. Supporting preschool children to meet all guidelines or more guidelines, particularly the sleep and screen time guidelines, may be beneficial for their social-cognitive development

New Policies, New Technologies: Modelling the Potential for Improved Smear Microscopy Services in Malawi

Background To quantify the likely impact of recent WHO policy recommendations regarding smear microscopy and the introduction of appropriate low-cost fluorescence microscopy on a) case detection and b) laboratory workload.Methodology/Principal Findings An audit of the laboratory register in an urban hospital, Lilongwe, Malawi, and the application of a simple modelling framework. The adoption of the new definition of a smear-positive case could directly increase case detection by up to 28%. Examining Ziehl-Neelsen (ZN) sputum smears for up to 10 minutes before declaring them negative has previously been shown to increase case detection (over and above that gained by the adoption of the new case definition) by 70% compared with examination times in routine practice. Three times the number of staff would be required to adequately examine the current workload of smears using ZN microscopy. Through implementing new policy recommendations and LED-based fluorescence microscopy the current laboratory staff complement could investigate the same number of patients, examining auramine-stained smears to an extent that is equivalent to a 10 minutes ZN smear examination.Conclusions/Significance Combined implementation of the new WHO recommendations on smear microscopy and LED-based fluorescence microscopy could result in substantial increases in smear positive case-detection using existing human resources and minimal additional equipment

Translational Database Selection and Multiplexed Sequence Capture for Up Front Filtering of Reliable Breast Cancer Biomarker Candidates

Biomarker identification is of utmost importance for the development of novel diagnostics and therapeutics. Here we make use of a translational database selection strategy, utilizing data from the Human Protein Atlas (HPA) on differentially expressed protein patterns in healthy and breast cancer tissues as a means to filter out potential biomarkers for underlying genetic causatives of the disease. DNA was isolated from ten breast cancer biopsies, and the protein coding and flanking non-coding genomic regions corresponding to the selected proteins were extracted in a multiplexed format from the samples using a single DNA sequence capture array. Deep sequencing revealed an even enrichment of the multiplexed samples and a great variation of genetic alterations in the tumors of the sampled individuals. Benefiting from the upstream filtering method, the final set of biomarker candidates could be completely verified through bidirectional Sanger sequencing, revealing a 40 percent false positive rate despite high read coverage. Of the variants encountered in translated regions, nine novel non-synonymous variations were identified and verified, two of which were present in more than one of the ten tumor samples

Calculation of ATP production rates using the Seahorse XF Analyzer

Oxidative phosphorylation and glycolysis are the dominant ATP-generating pathways in mammalian metabolism. The balance between these two pathways is often shifted to execute cell-specific functions in response to stimuli that promote activation, proliferation, or differentiation. However, measurement of these metabolic switches has remained mostly qualitative, making it difficult to discriminate between healthy, physiological changes in energy transduction or compensatory responses due to metabolic dysfunction. We therefore present a broadly applicable method to calculate ATP production rates from oxidative phosphorylation and glycolysis using Seahorse XF Analyzer data and empirical conversion factors. We quantify the bioenergetic changes observed during macrophage polarization as well as cancer cell adaptation to in vitro culture conditions. Additionally, we detect substantive changes in ATP utilization upon neuronal depolarization and T cell receptor activation that are not evident from steady-state ATP measurements. This method generates a single readout that allows the direct comparison of ATP produced from oxidative phosphorylation and glycolysis in live cells. Additionally, the manuscript provides a framework for tailoring the calculations to specific cell systems or experimental conditions