64 research outputs found

    Lifestyle factors and primary glioma and meningioma tumours in the Million Women Study cohort

    Get PDF
    Previous studies have reported inconsistent results on the effect of anthropometric and lifestyle factors on the risk of developing glioma or meningioma tumours. A prospective cohort of 1.3 million middle-aged women was used to examine these relationships. During 7.7 million women-years of follow-up, a total of 1563 women were diagnosed with a primary incident central nervous system tumour: 646 tumours were classified as glioma and 390 as meningioma. Our results show that height is related to the incidence of all central nervous system tumours with a risk of about 20% per 10 cm increase in height (relative risk=1.19, 95% CI=1.10–1.30 per 10 cm increase in height, P<0.001): the risks did not differ significantly between specified glioma and meningioma. Body mass index (BMI) was also related to central nervous system tumour incidence, with a risk of about 20% per 10 kg m−2 increase in BMI (relative risk=1.17, 95% CI=1.03–1.34 per 10 kg m−2 increase in BMI, P=0.02). Smoking status, alcohol intake, socioeconomic level, parity, age at first birth, and oral contraceptive use were not associated with the risk of glioma or meningioma tumours. In conclusion, for women in the United Kingdom, the incidence of glioma or meningioma tumours increases with increasing height and increasing BMI

    Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.

    Get PDF
    By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC50s) in the sub-micromolar and low micromolar range

    A latent growth curve model to estimate electronic screen use patterns amongst adolescents aged 10 to 17 years

    Get PDF
    Background: High quality, longitudinal data describing young people's screen use across a number of distinct forms of screen activity is missing from the literature. This study tracked multiple screen use activities (passive screen use, gaming, social networking, web searching) amongst 10- to 17-year-old adolescents across 24 months. Methods: This study tracked the screen use of 1948 Australian students in Grade 5 (n = 636), Grade 7 (n = 672), and Grade 9 (n = 640) for 24 months. At approximately six-month intervals, students reported their total screen time as well as time spent on social networking, passive screen use, gaming, and web use. Patterns of screen use were determined using latent growth curve modelling. Results: In the Grades 7 and 9 cohorts, girls generally reported more screen use than boys (by approximately one hour a day), though all cohorts of boys reported more gaming. The different forms of screen use were remarkably stable, though specific cohorts showed change for certain forms of screen activity. Conclusion: These results highlight the diverse nature of adolescent screen use and emphasise the need to consider both grade and sex in future research and policy

    Suicide with psychiatric diagnosis and without utilization of psychiatric service

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Considerable attention has been focused on the study of suicides among those who have received help from healthcare providers. However, little is known about the profiles of suicide deceased who had psychiatric illnesses but made no contact with psychiatric services prior to their death. Behavioural model of health service use is applied to identify factors associated with the utilization of psychiatric service among the suicide deceased.</p> <p>Methods</p> <p>With respect to completed suicide cases, who were diagnosed with a mental disorder, a comparison study was made between those who had (contact group; n = 52; 43.7%) and those who had not made any contact (non-contact group; n = 67; 56.3%) with a psychiatrist during the final six months prior to death. A <it>sample </it>of 119 deceased cases aged between 15 and 59 with at least one psychiatric diagnosis assessed by the Structured Clinical Interview for DSM-IV-TR (SCID I) were selected from a psychological autopsy study in Hong Kong.</p> <p>Results</p> <p>The contact and non-contact group could be well distinguished from each other by "<it>predisposing</it>" variables: age group & gender, and most of the "<it>enabling"</it>, and "<it>need" </it>variables tested in this study. Multiple logistic regression analysis has found four factors are statistically significantly associated with non-contact suicide deceased: (i) having non-psychotic disorders (OR = 13.5, 95% CI:2.9-62.9), (ii) unmanageable debts (OR = 10.5, CI:2.4-45.3), (iii) being full/partially/self employed at the time of death (OR = 10.0, CI:1.6-64.1) and (iv) having higher levels of social problem-solving ability (SPSI) (OR = 2.0, CI:1.1-3.6).</p> <p>Conclusion</p> <p>The non-contact group was clearly different from the contact group and actually comprised a larger proportion of the suicide population that they could hardly be reached by usual individual-based suicide prevention efforts. For this reason, both universal and strategic suicide prevention measures need to be developed specifically in non-medical settings to reach out to this non-contact group in order to achieve better suicide prevention results.</p

    Does economic development contribute to sex differences in ischaemic heart disease mortality? Hong Kong as a natural experiment using a case-control study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The male excess risk of premature ischemic heart disease (IHD) mortality may be partially due to an unknown macro-environmental influence associated with economic development. We examined whether excess male risk of IHD mortality was higher with birth in an economically developed environment.</p> <p>Methods</p> <p>We used multivariable logistic regression in a population-based case-control study of all adult deaths in Hong Kong Chinese in 1998 to compare sex differences in IHD mortality (1,189 deaths in men, 1,035 deaths in women and 20,842 controls) between Hong Kong residents born in economically developed Hong Kong or in contemporaneously undeveloped Guangdong province in China.</p> <p>Results</p> <p>Younger (35–64 years) native-born Hong Kong men had a higher risk of IHD death than such women (odds ratio 2.91, 95% confidence interval 1.66 to 5.13), adjusted for age, socio-economic status and lifestyle. There was no such sex difference in Hong Kong residents who had migrated from Guangdong. There were no sex differences in pneumonia deaths by birth place.</p> <p>Conclusion</p> <p>Most of these people migrated as young adults; we speculate that environmentally mediated differences in pubertal maturation (when the male disadvantage in lipids and fat patterning emerges) may contribute to excess male premature IHD mortality in developed environments.</p

    Reciprocal relationships between trajectories of depressive symptoms and screen media use during adolescence

    Get PDF
    Adolescents are constantly connected with each other and the digital landscape through a myriad of screen media devices. Unprecedented access to the wider world and hence a variety of activities, particularly since the introduction of mobile technology, has given rise to questions regarding the impact of this changing media environment on the mental health of young people. Depressive symptoms are one of the most common disabling health issues in adolescence and although research has examined associations between screen use and symptoms of depression, longitudinal investigations are rare and fewer still consider trajectories of change in symptoms. Given the plethora of devices and normalisation of their use, understanding potential longitudinal associations with mental health is crucial. A sample of 1,749 (47% female) adolescents (10-17 years) participated in six waves of data collection over two years. Symptoms of depression, time spent on screens, and on separate screen activities (social networking, gaming, web browsing, TV/passive) were self-reported. Latent growth curve modelling revealed three trajectories of depressive symptoms (Low-Stable, High-Decreasing, and Low-Increasing) and there were important differences across these groups on screen use. Some small, positive associations were evident between depressive symptoms and later screen use, and between screen use and later depressive symptoms. However, a Random Intercept Cross Lagged Panel Model revealed no consistent support for a longitudinal association. The study highlights the importance of considering differential trajectories of depressive symptoms and specific forms of screen activity to understand these relationships

    Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders

    Get PDF
    Turner syndrome (TS) is one of the most common sex chromosome abnormalities. Affected individuals often show a unique pattern of cognitive strengths and weaknesses and are at increased risk for a number of other neurodevelopmental conditions, many of which are more common in typical males than typical females (e.g., autism and attention-deficit hyperactivity disorder). This phenotype may reflect gonadal steroid deficiency, haploinsufficiency of X chromosome genes, failure to express parentally imprinted genes, and the uncovering of X chromosome mutations. Understanding the contribution of these different mechanisms to outcome has the potential to improve clinical care for individuals with TS and to better our understanding of the differential vulnerability to and expression of neurodevelopmental disorders in males and females. In this paper, we review what is currently known about cognition and brain development in individuals with TS, discuss underlying mechanisms and their relevance to understanding male-biased neurodevelopmental conditions, and suggest directions for future research

    Promotion, prevention and protection: interventions at the population- and community-levels for mental, neurological and substance use disorders in low- and middle-income countries

    Get PDF
    Background In addition to services within the health system, interventions at the population and community levels are also important for the promotion of mental health, primary prevention of mental, neurological and substance use (MNS) disorders, identification and case detection of MNS disorders; and to a lesser degree treatment, care and rehabilitation. This study aims to identify “best practice” and “good practice” interventions that can feasibly be delivered at these population- and community-levels in low- and middle-income countries (LMICs), to aid the identification of resource efficiencies and allocation in LMICs. Methods A narrative review was conducted given the wide range of relevant interventions. Expert consensus was used to identify “best practice” at the population-level on the basis of existing quasi-experimental natural experiments and cost effectiveness, with small scale emerging and promising evidence comprising “good practice”. At the community-level, using expert consensus, the ACE (Assessing Cost-Effectiveness in Prevention Project) grading system was used to differentiate “best practice” interventions with sufficient evidence from “good practice” interventions with limited but promising evidence. ResultsAt the population-level, laws and regulations to control alcohol demand and restrict access to lethal means of suicide were considered “best practice”. Child protection laws, improved control of neurocysticercosis and mass awareness campaigns were identified as “good practice”. At the community level, socio-emotional learning programmes in schools and parenting programmes during infancy were identified as “best practice”. The following were all identified as “good practice”: Integrating mental health promotion strategies into workplace occupational health and safety policies; mental health information and awareness programmes as well as detection of MNS disorders in schools; early child enrichment/preschool educational programs and parenting programs for children aged 2–14 years; gender equity and/or economic empowerment programs for vulnerable groups; training of gatekeepers to identify people with MNS disorders in the community; and training non-specialist community members at a neighbourhood level to assist with community-based support and rehabilitation of people with mental disorders. Conclusion Interventions provided at the population- and community-levels have an important role to play in promoting mental health, preventing the onset, and protecting those with MNS disorders. The importance of inter-sectoral enga
    corecore