3,758 research outputs found

    Collapse of a Bose gas: kinetic approach

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    We have analytically explored temperature dependence of critical number of particles for the collapse of a harmonically trapped attractively interacting Bose gas below the condensation point by introducing a kinetic approach within the Hartree-Fock approximation. The temperature dependence obtained by this easy approach is consisted with that obtained from the scaling theory.Comment: Brief Report, 4 pages, 1 figure, Accepted in Pramana-Journal of Physic

    Stabilization of nontoxic Ajβ-oligomers: Insights into the mechanism of action of hydroxyquinolines in alzheimer’s disease

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    ©2015 the authors. The extracellular accumulation of amyloid β (A/β) peptides is characteristic of Alzheimer's disease (AD). However, formation of diffusible, oligomeric forms of Aβ, both on and off pathways to amyloid fibrils, is thought to include neurotoxic species responsible for synaptic loss and neurodegeneration, rather than polymeric amyloid aggregates. The 8-hydroxyquinolines (8-HQ) clioquinol (CQ) and PBT2 were developed for their ability to inhibit metal-mediated generation of reactive oxygen species from A/β:Cu complexes and have both undergone preclinical and Phase II clinical development for the treatment of AD. Their respective modes of action are not fully understood and may include both inhibition of Aβ fibrillar polymerization and direct depolymerization of existing Aβ fibrils. In the present study, we find that CQ and PBT2 can interact directly with Aβ and affect its propensity to aggregate. Using a combination of biophysical techniques, we demonstrate that, in the presence of these 8-HQs and in the absence of metal ions, Aβ associates with two 8-HQ molecules and forms a dimer. Furthermore, 8-HQ bind Aβ with an affinity of 1-10 μam and suppress the formation of large (>30kDa) oligomers. The stabilized low molecular weight species are nontoxic. Treatment with 8-HQs also reduces the levels of in vivo soluble oligomers in a Caenorhabditis elegans model of Aβ toxicity. We propose that 8-HQs possess an additional mechanism of action that neutralizes neurotoxic Aβ oligomer formation through stabilization of small (dimeric) nontoxic Aβ conformers

    Personal health promotion at US medical schools: a quantitative study and qualitative description of deans' and students' perceptions

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    BACKGROUND: Prior literature has shown that physicians with healthy personal habits are more likely to encourage patients to adopt similar habits. However, despite the possibility that promoting medical student health might therefore efficiently improve patient outcomes, no one has studied whether such promotion happens in medical school. We therefore wished to describe both typical and outstanding personal health promotion environments experienced by students in U.S. medical schools. METHODS: We collected information through four different modalities: a literature review, written surveys of medical school deans and students, student and dean focus groups, and site visits at and interviews with medical schools with reportedly outstanding student health promotion programs. RESULTS: We found strong correlations between deans' and students' perceptions of their schools' health promotion environments, including consistent support of the idea of schools' encouraging healthy student behaviors, with less consistent follow-through by schools on this concept. Though students seemed to have thought little about the relationships between their own personal and clinical health promotion practices, deans felt strongly that faculty members should model healthy behaviors. CONCLUSIONS: Deans' support of the relationship between physicians' personal and clinical health practices, and concern about their institutions' acting on this relationship augurs well for the role of student health promotion in the future of medical education. Deans seem to understand their students' health environment, and believe it could and should be improved; if this is acted on, it could create important positive changes in medical education and in disease prevention

    Clinical characteristics of pertussis-associated cough in adults and children: a diagnostic systematic review and meta-analysis

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    Background: Pertussis (whooping cough) is a highly infective cause of cough that causes significant morbidity and mortality. Existing case definitions include paroxysmal cough, whooping and post-tussive vomiting but diagnosis can be difficult. We determined the diagnostic accuracy of clinical characteristics of pertussis-associated cough. Methods: We systematically searched CINAHL, Embase, Medline and SCI-EXPANDED/CPCI-S up to June 2016. Eligible studies compared clinical characteristics in those positive and negative for Bordetella pertussis infection, confirmed by laboratory investigations. Two authors independently completed screening, data extraction and quality and bias assessments. For each characteristic RevMan was used to produce descriptive forest plots. We used the bivariate meta-analysis method to generate pooled estimates of sensitivity and specificity. Results: Of 1969 identified papers, 53 were included. Forty-one clinical characteristics were assessed for diagnostic accuracy. In adult patients, paroxysmal cough and absence of fever had a high sensitivity (93.2%, CI 83.2-97.4 and 81.8%, CI 72.2-88.7 respectively) and low specificity (20.6%, CI 14.7-28.1 and 18.8%, CI 8.1-37.9 respectively), whereas post-tussive vomiting and whooping had low sensitivity (32.5%, CI 24.5-41.6 and 29.8%, CI 8.0-45.2 respectively) and high specificity (77.7%, CI 73.1-81.7 and 79.5%, CI 69.4-86.9 respectively). Post-tussive vomiting in children is moderately sensitive (60.0%, CI 40.3-77.0) and specific 66.0%, CI 52.5-77.3). Conclusions: In adult patients the presence of whooping or post-tussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children, post-tussive vomiting is much less helpful as a clinical diagnostic test

    Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress

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    Endoplasmic reticulum (ER) stress triggers apoptosis by activating Bim in diverse types of cells, which involves dephosphorylation of BimEL by protein phosphatase 2A (PP2A). However, melanoma cells are largely resistant to ER stress-induced apoptosis, suggesting that Bim activation is suppressed in melanoma cells undergoing ER stress. We show here that ER stress reduces PP2A activity leading to increased ERK activation and subsequent phosphorylation and proteasomal degradation of BimEL. Despite sustained upregulation of Bim at the transcriptional level, the BimEL protein expression was downregulated after an initial increase in melanoma cells subjected to pharmacological ER stress. This was mediated by increased activity of ERK, whereas the phosphatase activity of PP2A was reduced by ER stress in melanoma cells. The increase in ERK activation was, at least in part, due to reduced dephosphorylation by PP2A, which was associated with downregulation of the PP2A catalytic C subunit. Notably, instead of direct dephosphorylation of BimEL, PP2A inhibited its phosphorylation indirectly through dephosphorylation of ERK in melanoma cells. Taken together, these results identify downregualtion of PP2A activity as an important protective mechanism of melanoma cells against ER stress-induced apoptosis

    Optimising antimicrobial stewardship interventions in English primary care: a behavioural analysis of qualitative and intervention studies

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    Objective: While various interventions have helped reduce antibiotic prescribing, further gains can be made. This study aimed to identify ways to optimise antimicrobial stewardship (AMS) interventions by assessing the extent to which important influences on antibiotic prescribing are addressed (or not) by behavioural content of AMS interventions. Settings: English primary care. Interventions: AMS interventions targeting healthcare professionals’ antibiotic prescribing for respiratory tract infections. Methods: We conducted two rapid reviews. The first included qualitative studies with healthcare professionals on self-reported influences on antibiotic prescribing. The influences were inductively coded and categorised using the Theoretical Domains Framework (TDF). Prespecified criteria were used to identify key TDF domains. The second review included studies of AMS interventions. Data on effectiveness were extracted. Components of effective interventions were extracted and coded using the TDF, Behaviour Change Wheel and Behaviour Change Techniques (BCTs) taxonomy. Using prespecified matrices, we assessed the extent to which BCTs and intervention functions addressed the key TDF domains of influences on prescribing. Results: We identified 13 qualitative studies, 41 types of influences on antibiotic prescribing and 6 key TDF domains of influences: ‘beliefs about consequences’, ‘social influences’, ‘skills’, ‘environmental context and resources’, ‘intentions’ and ‘emotions’. We identified 17 research-tested AMS interventions; nine of them effective and four nationally implemented. Interventions addressed all six key TDF domains of influences. Four of these six key TDF domains were addressed by 50%–67% BCTs that were theoretically congruent with these domains, whereas TDF domain 'skills' was addressed by 24% of congruent BCTs and 'emotions' by none. Conclusions: Further improvement of antibiotic prescribing could be facilitated by: (1) national implementation of effective research-tested AMS interventions (eg, electronic decision support tools, training in interactive use of leaflets, point-of-care testing); (2) targeting important, less-addressed TDF domains (eg, 'skills', 'emotions'); (3) using relevant, under-used BCTs to target key TDF domains (eg, ‘forming/reversing habits’, ‘reducing negative emotions’, ‘social support’). These could be incorporated into existing, or developed as new, AMS interventions

    Optimising interventions for catheter-associated urinary tract infections (Cauti) in primary, secondary and care home settings

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    Catheter-associated urinary tract infections (CAUTI) are common yet preventable. Healthcare professional behaviours, such as reducing unnecessary catheter use, are key for preventing CAUTI. Previous research has focused on identifying gaps in the national response to CAUTI in multiple settings in England. This study aimed to identify how national interventions could be optimised. We conducted a multi-method study comprising: a rapid review of research on interventions to reduce CAUTI; a behavioural analysis of effective research interventions compared to national interventions; and a stakeholder focus group and survey to identify the most promising options for optimising interventions. We identified 37 effective research interventions, mostly conducted in United States secondary care. A behavioural analysis of these interventions identified 39 intervention components as possible ways to optimise national interventions. Seven intervention components were prioritised by stakeholders. These included: checklists for discharge/admission to wards; information for patients and relatives about the pros/cons of catheters; setting and profession specific guidelines; standardised nationwide computer-based documentation; promotion of alternatives to catheter use; CAUTI champions; and bladder scanners. By combining research evidence, behavioural analysis and stakeholder feedback, we identified how national interventions to reduce CAUTI could be improved. The seven prioritised components should be considered for future implementation
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