Risk of malignant lymphoma associated with human herpesvirus-8: a case–control study in Spain

No overall increased risk of lymphoma associated with antibodies to human herpesvirus-8 was found in 526 lymphomas and 599 controls (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.62-1.75); significant increases were noted for 19 lymphoplasmacytic lymphomas (OR=4.47, 95% CI=1.34-14.85) and nine low-grade lymphoma/lymphoma B-cell NOS (OR=5.82, 95% CI=1.07-31.73)

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Estimating genomic instability mediated by Alu retroelements in breast cancer

Alu-PCR is a relatively simple technique that can be used to investigate genomic instability in cancer. This technique allows identification of the loss, gain or amplification of gene sequences based on the analysis of segments between two Alu elements coupled with quantitative and qualitative analyses of the profiles obtained from tumor samples, surgical margins and blood. In this work, we used Alu-PCR to identify gene alterations in ten patients with invasive ductal breast cancer. Several deletions and insertions were identified, indicating genomic instability in the tumor and adjacent normal tissue. Although not associated with specific genes, the alterations, which involved chromosomal bands 1p36.23, 1q41, 11q14.3, 13q14.2, occurred in areas of well-known genomic instability in breast and other types of cancer. These results indicate the potential usefulness of Alu-PCR in identifying altered gene sequences in breast cancer. However, caution is required in its application since the Alu primer can produce non-specific amplification

The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use

The CLIMATE schools combined study: a cluster randomised controlled trial of a universal Internet-based prevention program for youth substance misuse, depression and anxiety

Background: Anxiety, depressive and substance use disorders account for three quarters of the disability attributed to mental disorders and frequently co-occur. While programs for the prevention and reduction of symptoms associated with (i) substance use and (ii) mental health disorders exist, research is yet to determine if a combined approach is more effective. This paper describes the study protocol of a cluster randomised controlled trial to evaluate the effectiveness of the CLIMATE Schools Combined intervention, a universal approach to preventing substance use and mental health problems among adolescents. Methods/design: Participants will consist of approximately 8400 students aged 13 to 14-years-old from 84 secondary schools in New South Wales, Western Australia and Queensland, Australia. The schools will be cluster randomised to one of four groups; (i) CLIMATE Schools Combined intervention; (ii) CLIMATE Schools - Substance Use; (iii) CLIMATE Schools - Mental Health, or (iv) Control (Health and Physical Education as usual). The primary outcomes of the trial will be the uptake and harmful use of alcohol and other drugs, mental health symptomatology and anxiety, depression and substance use knowledge. Secondary outcomes include substance use related harms, self-efficacy to resist peer pressure, general disability, and truancy. The link between personality and substance use will also be examined.Discussion: Compared to students who receive the universal CLIMATE Schools - Substance Use, or CLIMATE Schools - Mental Health or the Control condition (who received usual Health and Physical Education), we expect students who receive the CLIMATE Schools Combined intervention to show greater delays to the initiation of substance use, reductions in substance use and mental health symptoms, and increased substance use and mental health knowledge

Policy challenges for the pediatric rheumatology workforce: Part II. Health care system delivery and workforce supply

The United States pediatric population with chronic health conditions is expanding. Currently, this demographic comprises 12-18% of the American child and youth population. Affected children often receive fragmented, uncoordinated care. Overall, the American health care delivery system produces modest outcomes for this population. Poor, uninsured and minority children may be at increased risk for inferior coordination of services. Further, the United States health care delivery system is primarily organized for the diagnosis and treatment of acute conditions. For pediatric patients with chronic health conditions, the typical acute problem-oriented visit actually serves as a barrier to care. The biomedical model of patient education prevails, characterized by unilateral transfer of medical information. However, the evidence basis for improvement in disease outcomes supports the use of the chronic care model, initially proposed by Dr. Edward Wagner. Six inter-related elements distinguish the success of the chronic care model, which include self-management support and care coordination by a prepared, proactive team

Swiss residents' speciality choices – impact of gender, personality traits, career motivation and life goals

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the development of health-care services. This study aimed to investigate the influence of gender, personality traits, career motivation and life goal aspirations on the choice of medical speciality. METHODS: As part of a prospective cohort study of Swiss medical school graduates on career development, 522 fourth-year residents were asked in what speciality they wanted to qualify. They also assessed their career motivation and life goal aspirations. Data concerning personality traits such as sense of coherence, self-esteem, and gender role orientation were collected at the first assessment, four years earlier, in their final year of medical school. Data analyses were conducted by univariate and multivariate analyses of variance and covariance. RESULTS: In their fourth year of residency 439 (84.1%) participants had made their speciality choice. Of these, 45 (8.6%) subjects aspired to primary care, 126 (24.1%) to internal medicine, 68 (13.0%) to surgical specialities, 31 (5.9%) to gynaecology & obstetrics (G&O), 40 (7.7%) to anaesthesiology/intensive care, 44 (8.4%) to paediatrics, 25 (4.8%) to psychiatry and 60 (11.5%) to other specialities. Female residents tended to choose G&O, paediatrics, and anaesthesiology, males more often surgical specialities; the other specialities did not show gender-relevant differences of frequency distribution. Gender had the strongest significant influence on speciality choice, followed by career motivation, personality traits, and life goals. Multivariate analyses of covariance indicated that career motivation and life goals mediated the influence of personality on career choice. Personality traits were no longer significant after controlling for career motivation and life goals as covariates. The effect of gender remained significant after controlling for personality traits, career motivation and life goals. CONCLUSION: Gender had the greatest impact on speciality and career choice, but there were also two other relevant influencing factors, namely career motivation and life goals. Senior physicians mentoring junior physicians should pay special attention to these aspects. Motivational guidance throughout medical training should not only focus on the professional career but also consider the personal life goals of those being mentored

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart

The learning styles neuromyth:when the same term means different things to different teachers

Alexia Barrable - ORCID: 0000-0002-5352-8330 https://orcid.org/0000-0002-5352-8330Although learning styles (LS) have been recognised as a neuromyth, they remain a virtual truism within education. A point of concern is that the term LS has been used within theories that describe them using completely different notions and categorisations. This is the first empirical study to investigate education professionals’ conceptualisation, as well as means of identifying and implementing LS in their classroom. A sample of 123 education professionals were administered a questionnaire consisting both closed- and open-ended questions. Responses were analysed using thematic analysis. LS were found to be mainly conceptualised within the Visual-Auditory-(Reading)-Kinaesthetic (VAK/VARK) framework, as well as Gardner’s multiple intelligences. Moreover, a lot of education professionals confused theories of learning (e.g., behavioural or cognitive theories) with LS. In terms of identifying LS, educators reported using a variety of methods, spanning from observation and everyday contact to the use of tests. The ways LS were implemented in the classroom were numerous, comprising various teaching aids, participatory techniques and motor activities. Overall, we argue that the extended use of the term LS gives the illusion of a consensus amongst educators, when a closer examination reveals that the term LS is conceptualised, identified and implemented idiosyncratically by different individuals. This study aims to be of use to pre-service and in-service teacher educators in their effort to debunk the neuromyth of LS and replace it with evidence-based practices.https://doi.org/10.1007/s10212-020-00485-236pubpub