A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management

In a case of astroblastoma, methylation analysis was uninformative, with no clustering with known CNS-HGNET-MN1 cases. Whole genome sequencing however identified a novel MN1-GTSE1 gene fusion (image), confirming the diagnosis of astroblastoma, as well as an EWSR1-PATZ1 gene fusion. Whole genome sequencing, alongside methylation profiling and conventional neuropathology, will continue to lead to improved diagnostics and prognostication for children with brain tumours

Cardiac Potassium Channels: Physiological Insights for Targeted Therapy.

The development of novel drugs specifically directed at the ion channels underlying particular features of cardiac action potential (AP) initiation, recovery, and refractoriness would contribute to an optimized approach to antiarrhythmic therapy that minimizes potential cardiac and extracardiac toxicity. Of these, K(+) channels contribute numerous and diverse currents with specific actions on different phases in the time course of AP repolarization. These features and their site-specific distribution make particular K(+) channel types attractive therapeutic targets for the development of pharmacological agents attempting antiarrhythmic therapy in conditions such as atrial fibrillation. However, progress in the development of such temporally and spatially selective antiarrhythmic drugs against particular ion channels has been relatively limited, particularly in view of our incomplete understanding of the complex physiological roles and interactions of the various ionic currents. This review summarizes the physiological properties of the main cardiac potassium channels and the way in which they modulate cardiac electrical activity and then critiques a number of available potential antiarrhythmic drugs directed at them

Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states

Over two-thirds of integral membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study, we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 C

Liberalization, globalization and the dynamics of democracy in India

In the closing decades of the twentieth century there has been an almost complete intellectual triumph of the twin principles of marketization (understood here as referring to the liberalization of domestic markets and freer international mobility of goods, services, financial capital and perhaps, more arguably, labour) and democratization . A paradigm shift of this extent and magnitude would not have occurred in the absence of some broad consensus among policymakers and (sections of) intellectuals around the globe on the desirability of such a change. There seems to be a two-fold causal nexus between marketization and democracy. The first is more direct, stemming from the fact of both systems sharing certain values and attitudes in common. But there is also a second more indirect chain from marketization to democracy, which is predicated via three sub-chains (i) from marketization to growth, (ii) from growth to overall material development welfare and (iii) from material development to social welfare and democracy. We examine each of these sub-links in detail with a view to obtaining a greater understanding of the hypothesized role of free markets in promoting democracies. In the later part of the paper we examine the socio-economic outcomes governing the quality of democracy in a specifically Indian context

WPA position statement on prisoner mental and public health care

As a group, prisoners have a tendency not to engage effectively with healthcare services while they are in the community because they have so many other competing priorities. Other priorities may include access to adequate finance, finding a place to sleep that is dry and safe, having sufficient food for themselves and their families, or the need to meet existing addictions. However, as a group, they present with high levels of health morbidity across domains of physical and mental health and addictions. It is widely established that screening people for healthcare conditions at the point when they are received into prison can assist in identifying a range of medical conditions. Although the process has limitations, the practice of screening is recommended internationally. After screening has taken place, healthcare services are meant to be provided in prisons to the same extent and quality as would be available in the community, yet across the world, there have often been problems in ensuring the adequacy of prison healthcare systems. Prison healthcare departments have often lagged behind regarding funding, and many countries have reported problems with the quality and consistency of delivery. Also, issues with training and continuous professional development are often cited as problematic in this area. This curriculum has been prepared to assist countries in ensuring that systems are in place for the effective training and continuous professional development of staff. It is meant to assist those who design such programs for local use

Analysis of Endocytic Pathways in Drosophila Cells Reveals a Conserved Role for GBF1 in Internalization via GEECs

In mammalian cells, endocytosis of the fluid phase and glycosylphosphatidylinositol-anchored proteins (GPI-APs) forms GEECs (GPI-AP enriched early endosomal compartments) via an Arf1- and Cdc42-mediated, dynamin independent mechanism. Here we use four different fluorescently labeled probes and several markers in combination with quantitative kinetic assays, RNA interference and high resolution imaging to delineate major endocytic routes in Drosophila cultured cells. We find that the hallmarks of the pinocytic GEEC pathway are conserved in Drosophila and identify garz, the fly ortholog of the GTP exchange factor GBF1, as a novel component of this pathway. Live confocal and TIRF imaging reveals that a fraction of GBF1 GFP dynamically associates with ABD RFP (a sensor for activated Arf1 present on nascent pinosomes). Correspondingly, a GTP exchange mutant of GBF1 has altered ABD RFP localization in the evanescent field and is impaired in fluid phase uptake. Furthermore, GBF1 activation is required for the GEEC pathway even in the presence of Brefeldin A, implying that, like Arf1, it has a role in endocytosis that is separable from its role in secretion

Development and psychometric properties the Barriers to Access to Care Evaluation scale (BACE) related to people with mental ill health

Many people with mental illness do not seek or delay seeking care. This study aimed to develop, and provide an initial validation of, a comprehensive measure for assessing barriers to access to mental health care including a 'treatment stigma' subscale, and to present preliminary evidence about the prevalence of barriers experienced by adults currently or recently using secondary mental health services in the UK

Prevalence and correlates of smoking among urban adult men in Bangladesh: slum versus non-slum comparison

Khan MH, Khan A, Krämer A, Mori M. Prevalence and correlates of smoking among urban adult men in Bangladesh: slum versus non-slum comparison. BMC Public Health. 2009;9(1):149.Background: Smoking is one of the leading causes of premature death particularly in developing countries. The prevalence of smoking is high among the general male population in Bangladesh. Unfortunately smoking information including correlates of smoking in the cities especially in the urban slums is very scarce, although urbanization is rapid in Bangladesh and slums are growing quickly in its major cities. Therefore this study reported prevalences of cigarette and bidi smoking and their correlates separately by urban slums and non-slums in Bangladesh. Methods: We used secondary data which was collected by the 2006 Urban Health Survey. The data were representative for the urban areas in Bangladesh. Both slums and non-slums located in the six City Corporations were considered. Slums in the cities were identified by two steps, first by using the satellite images and secondly by ground truthing. At the next stage, several clusters of households were selected by using proportional sampling. Then from each of the selected clusters, about 25 households were randomly selected. Information of a total of 12,155 adult men, aged 15 59 years, was analyzed by stratifying them into slum (= 6,488) and non-slum (= 5,667) groups. Simple frequency, bivariable and multivariable logistic regression analyses were performed using SPSS. Results: Overall smoking prevalence for the total sample was 53.6% with significantly higher prevalences among men in slums (59.8%) than non-slums (46.4%). Respondents living in slums reported a significantly (P < 0.001) higher prevalence of smoking cigarettes (53.3%) as compared to those living in non-slums (44.6%). A similar pattern was found for bidis (slums = 11.4% and non-slums = 3.2%, P < 0.001). Multivariable logistic regression revealed significantly higher odds ratio (OR) of smoking cigarettes (OR = 1.12, 95% CI = 1.03-1.22), bidis (OR = 1.90, 95% CI = 1.58-2.29) and any of the two (OR = 1.23, 95% CI = 1.13-1.34) among men living in slums as compared to those living in non-slums when controlled for age, division, education, marital status, religion, birth place and types of work. Division, education and types of work were the common significant correlates for both cigarette and bidi smoking in slums and non-slums by multivariable logistic regressions. Other significant correlates of smoking cigarettes were marital status (both areas), birth place (slums), and religion (non-slums). Similarly significant factors for smoking bidis were age (both areas), marital status (slums), religion (non-slums), and birth place (both areas). Conclusion: The men living in the urban slums reported higher rates of smoking cigarettes and bidis as compared to men living in the urban non-slums. Some of the significant correlates of smoking e. g. education and division should be considered for prevention activities. Our findings clearly underscore the necessity of interventions and preventions by policy makers, public health experts and other stakeholders in slums because smoking was more prevalent in the slum communities with detrimental health sequelae

Attitudes and burden in relatives of patients with schizophrenia in a middle income country

BACKGROUND: Most studies of family attitudes and burden have been conducted in developed countries. Thus it is important to test the generalizability of this research in other contexts where social conditions and extended family involvement may be different. The aim of this study was to assess the relationship between the attitudes of caregivers and the burden they experience in such a context, namely Arica, a town located in the northernmost region of Chile, close to the border with Peru and Bolivia. METHODS: We assessed attitudes towards schizophrenia (including affective, cognitive and behavioural components) and burden (including subjective distress, rejection and competence) in 41 main caregivers of patients with schizophrenia, all of whom were users of Public Mental Health Services in Arica. RESULTS: Attitude measures differed significantly according to socio-demographic variables, with parents (mainly mothers) exhibiting a more negative attitude towards the environment than the rest of the family (t = 4.04; p = 0.000).This was also the case for caregivers with a low educational level (t = 3.27; p < 0.003), for the oldest caregivers (r = 0.546; p = 0.000) and for those who had spent more time with the patient (r = 0.377; p = 0.015). Although attitudes had significant association with burden, their explanatory power was modest (R2 = .104, F = 4,55; p = .039). CONCLUSIONS: Similar to finding developed countries, the current study revealed a positive and significant relationship between the attitudes of caregivers and their burden. These findings emphasize the need to support the families of patients with schizophrenia in this social context