458 research outputs found

    Esophageal perforation secondary to malignant gastric outlet obstruction: a case report

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    Background Esophageal perforation is a rare presenting sign of gastric cancer. To date, only nine case reports of this phenomenon have been previously published. Case presentation Esophageal perforation was diagnosed radiographically during workup for acute chest pain in a 67-year-old man. Emergent endoscopy confirmed esophageal perforation and biopsied a pre-pyloric mass confirmed to be adenocarcinoma. The perforation was managed with endoscopically placed transluminal pleural and mediastinal drains and esophageal stenting. The gastric outlet obstruction was temporized with a transpyloric stent. After the patient recovered from sepsis, distal gastrectomy was performed and he made a full recovery. Conclusions Rarely, pre-pyloric gastric cancer can present with Boerhaave syndrome, spontaneous esophageal perforation associated with forceful vomiting. We present the tenth report in the literature of this phenomenon and the first to be initially treated with endoscopic stenting and transluminal thoracoscopic drainage. When endoscopic management is used to treat patients with Boerhaave syndrome, it may be beneficial to examine the entire stomach to evaluate for malignant etiology

    Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

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    Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

    Mental health literacy as a function of remoteness of residence: an Australian national study

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    <p>Abstract</p> <p>Background</p> <p>Although there have been many population studies of mental health literacy, little is known about the mental health literacy of people who reside in rural areas. This study sought to determine the impact of remoteness on public knowledge of depression and schizophrenia.</p> <p>Methods</p> <p>The mental health literacy of residents of major cities, inner regional, and outer-remote (including outer regional, remote, and very remote) regions were compared using data from a 2003–04 Australian national survey of the mental health literacy of 3998 adults. Measures included the perceived helpfulness of a range of professionals, non-professionals and interventions, and the causes, prognosis, and outcomes after treatment for four case vignettes describing depression, depression with suicidal ideation, early schizophrenia and chronic schizophrenia. Participant awareness of Australia's national depression initiative and depression in the media, their symptoms of depression and exposure to the conditions depicted in the vignettes were also compared.</p> <p>Results</p> <p>Mental health literacy was similar across remoteness categories. However, inner regional residents showed superior identification of the disorders depicted in the suicidal ideation and chronic schizophrenia vignettes. They were also more likely to report having heard of Australia's national depression health promotion campaign. Conversely, they were less likely than major city residents to rate the evidence-based treatment of psychotherapy helpful for depression. Both inner regional and outer-remote residents were less likely to rate psychologists as helpful for depression alone. The rural groups were more likely to rate the non-evidence based interventions of drinking and painkillers as helpful for a depression vignette. In addition, outer-remote residents were more likely to identify the evidence based treatment of antipsychotics as harmful for early schizophrenia and less likely to endorse psychiatrists, psychologists, social workers and general practitioners as helpful for the condition.</p> <p>Conclusion</p> <p>Mental health awareness campaigns in rural and remote regions may be most appropriately focused on communicating which interventions are effective for depression and schizophrenia and which mental health and other professionals are trained in the best-practice delivery and management of these. There is also a need to communicate to rural residents that alcohol and pain relievers are not an effective solution for depression.</p

    Vitamin D in the general population of young adults with autism in the Faroe Islands

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    Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism

    A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

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    Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

    A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

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    The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

    A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients

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    <p>Abstract</p> <p>Background</p> <p>Patients with severe mental illness are at increased risk for metabolic and cardiovascular disease. A number of recent guidelines and consensus statements recommend stringent monitoring of metabolic function in individuals receiving antipsychotic drugs.</p> <p>Methods</p> <p>We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices.</p> <p>Results</p> <p>A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD ± 235.4) days. Body mass index (p < 0.005) and waist circumference (p < 0.05) had significantly increased at follow-up, as had the number of individuals who were either overweight or obese. Fifty-three per cent of individuals had hypertriglyceridemia, and 31% had hypercholesterolemia, but only 7% were receiving lipid-lowering therapy. Monitoring practices were poor. Recording of measures of adiposity occurred in 0% of individuals, and > 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period.</p> <p>Conclusion</p> <p>This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.</p

    A population study comparing screening performance of prototypes for depression and anxiety with standard scales

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    <p>Abstract</p> <p>Background</p> <p>Screening instruments for mental disorders need to be short, engaging, and valid. Current screening instruments are usually questionnaire-based and may be opaque to the user. A prototype approach where individuals identify with a description of an individual with typical symptoms of depression, anxiety, social phobia or panic may be a shorter, faster and more acceptable method for screening. The aim of the study was to evaluate the accuracy of four new prototype screeners for predicting depression and anxiety disorders and to compare their performance with existing scales.</p> <p>Methods</p> <p>Short and ultra-short prototypes were developed for Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), Panic Disorder (PD) and Social Phobia (SP). Prototypes were compared to typical short and ultra-short self-report screening scales, such as the Centre for Epidemiology Scale, CES-D and the GAD-7, and their short forms. The Mini International Neuropsychiatric Interview (MINI) version 6 <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> was used as the gold standard for obtaining clinical criteria through a telephone interview. From a population sample, 225 individuals who endorsed a prototype and 101 who did not were administered the MINI. Receiver operating characteristic (ROC) curves were plotted for the short and ultra short prototypes and for the short and ultra short screening scales.</p> <p>Results</p> <p>The study found that the rates of endorsement of the prototypes were commensurate with prevalence estimates. The short-form and ultra short scales outperformed the short and ultra short prototypes for every disorder except GAD, where the GAD prototype outperformed the GAD 7.</p> <p>Conclusions</p> <p>The findings suggest that people may be able to self-identify generalised anxiety more accurately than depression based on a description of a prototypical case. However, levels of identification were lower than expected. Considerable benefits from this method of screening may ensue if our prototypes can be improved for Major Depressive Disorder, Social Phobia and Panic Disorder.</p
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