Mast Cells Granular Contents Are Crucial for Deep Vein Thrombosis in Mice

Rationale: Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. Objective: We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. Methods and Results: In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava. We demonstrated that 2 strains of mice deficient for MCs were completely protected from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis. MCs were present in the venous wall, and the number of granule-containing MCs decreased with thrombosis. Pharmacological depletion of MCs granules or prevention of MC degranulation also reduced DVT. Basal plasma levels of von Willebrand factor and recruitment of platelets to the inferior vena cava wall after DVT induction were reduced in MC-deficient mice. Stenosis application increased plasma levels of soluble P-selectin in wild-type but not in MC-deficient mice. MC releasate elevated ICAM-1 (intercellular adhesion molecule-1) expression on HUVEC (human umbilical vein endothelial cells) in vitro. Topical application of compound 48/80, an MC secretagogue, or histamine, a Weibel–Palade body secretagogue from MCs, potentiated DVT in wild-type mice, and histamine restored thrombosis in MC-deficient animals. Conclusions: MCs exacerbate DVT likely through endothelial activation and Weibel–Palade body release, which is, at least in part, mediated by histamine. Because MCs do not directly contribute to normal hemostasis, they can be considered potential targets for prevention of DVT in humans

Investigating the influence of African American and African Caribbean race on primary care doctors' decision making about depression

This paper explores differences in how primary care doctors process the clinical presentation of depression by African American and African-Caribbean patients compared with white patients in the US and the UK. The aim is to gain a better understanding of possible pathways by which racial disparities arise in depression care. One hundred and eight doctors described their thought processes after viewing video recorded simulated patients presenting with identical symptoms strongly suggestive of depression. These descriptions were analysed using the CliniClass system, which captures information about micro-components of clinical decision making and permits a systematic, structured and detailed analysis of how doctors arrive at diagnostic, intervention and management decisions. Video recordings of actors portraying black (both African American and African-Caribbean) and white (both White American and White British) male and female patients (aged 55 years and 75 years) were presented to doctors randomly selected from the Massachusetts Medical Society list and from Surrey/South West London and West Midlands National Health Service lists, stratified by country (US v.UK), gender, and years of clinical experience (less v. very experienced). Findings demonstrated little evidence of bias affecting doctors' decision making processes, with the exception of less attention being paid to the potential outcomes associated with different treatment options for African American compared with White American patients in the US. Instead, findings suggest greater clinical uncertainty in diagnosing depression amongst black compared with white patients, particularly in the UK. This was evident in more potential diagnoses. There was also a tendency for doctors in both countries to focus more on black patients' physical rather than psychological symptoms and to identify endocrine problems, most often diabetes, as a presenting complaint for them. This suggests that doctors in both countries have a less well developed mental model of depression for black compared with white patients

A case-control study of determinants for high and low dental caries prevalence in Nevada youth

<p>Abstract</p> <p>Background</p> <p>The main purpose of this study was to compare the 30% of Nevada Youth who presented with the highest Decayed Missing and Filled Teeth (DMFT) index to a cohort who were caries free and to national NHANES data. Secondly, to explore the factors associated with higher caries prevalence in those with the highest DMFT scores compared to the caries-free group.</p> <p>Methods</p> <p>Over 4000 adolescents between ages 12 and 19 (Case Group: N = 2124; Control Group: N = 2045) received oral health screenings conducted in public/private middle and high schools in Nevada in 2008/2009 academic year. Caries prevalence was computed (Untreated decay scores [D-Score] and DMFT scores) for the 30% of Nevada Youth who presented with the highest DMFT score (case group) and compared to the control group (caries-free) and to national averages. Bivariate and multivariate logistic regression was used to analyze the relationship between selected variables and caries prevalence.</p> <p>Results</p> <p>A majority of the sample was non-Hispanic (62%), non-smokers (80%), and had dental insurance (70%). With the exception of gender, significant differences in mean D-scores were found in seven of the eight variables. All variables produced significant differences between the case and control groups in mean DMFT Scores. With the exception of smoking status, there were significant differences in seven of the eight variables in the bivariate logistic regression. All of the independent variables remained in the multivariate logistic regression model contributing significantly to over 40% of the variation in the increased DMFT status. The strongest predictors for the high DMFT status were racial background, age, fluoridated community, and applied sealants respectively. Gender, second hand smoke, insurance status, and tobacco use were significant, but to a lesser extent.</p> <p>Conclusions</p> <p>Findings from this study will aid in creating educational programs and other primary and secondary interventions to help promote oral health for Nevada youth, especially focusing on the subgroup that presents with the highest mean DMFT scores.</p

Obesity: An overview on its current perspectives and treatment options

Obesity is a multi-factorial disorder, which is often associated with many other significant diseases such as diabetes, hypertension and other cardiovascular diseases, osteoarthritis and certain cancers. The management of obesity will therefore require a comprehensive range of strategies focussing on those with existing weight problems and also on those at high risk of developing obesity. Hence, prevention of obesity during childhood should be considered a priority, as there is a risk of persistence to adulthood. This article highlights various preventive aspects and treatment procedures of obesity with special emphasis on the latest research manifolds

The Olympic Games and raising sports participation: a systematic review of evidence and an interrogation of policy for a demonstration effect

Research questions: Can a demonstration effect, whereby people are inspired by elite sport, sports people and events to actively participate themselves, be harnessed from an Olympic Games to influence sport participation? Did London 2012 sport participation legacy policy draw on evidence about a demonstration effect, and was a legacy delivered? Research methods: A worldwide systematic review of English language evidence returned 1,778 sources iteratively reduced by the author panel, on advice from an international review panel, to 21 included sources that were quality appraised and synthesised narratively. The evidence was used to examine the influence of a demonstration effect on sport participation engagement and to interrogate sport participation legacy policy for London 2012. Results and findings: There is no evidence for an inherent demonstration effect, but a potential demonstration effect, properly leveraged, may deliver increases in sport participation frequency and re-engage lapsed participants. Despite setting out to use London 2012 to raise sport participation, successive UK governments’ policy failures to harness the potential influence of a demonstration effect on demand resulted in failure to deliver increased participation. Implications: If the primary justification for hosting an Olympic Games is the potential impact on sport participation, the Games are a bad investment. However, the Games can have specific impacts on sport participation frequency and re-engagement, and if these are desirable for host societies, are properly leveraged by hosts, and are one among a number of reasons for hosting the Games, then the Games may be a justifiable investment in sport participation terms