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The actual suicide of Private Danny Chen: A great social concept perspective.
aureus, purR mutants have enhanced invasion of these non-professional phagocytes, consistent with the requirement of FnBPs for invasion of these cells. This correlates with purR mutants having both increased transcription of fnb genes, resulting in higher levels of surface-exposed FnBPs to promote invasion. These data provide important contributions to our understanding of how the pathogenesis of S. aureus is affected by sensing of purine levels during infection of the mammalian host. Copyright © 2020 Goncheva et al.Chronic bacterial infections are caused by pathogens that persist within their hosts and avoid clearance by the immune system. Treatment and/or detection of such pathogens is difficult, and the resulting pathologies are often deleterious or fatal. There is an urgent need to develop protective vaccines and host-directed therapies that synergize with antibiotics to prevent pathogen persistence and infection-associated pathologies. However, many persistent pathogens, such as Mycobacterium tuberculosis, actively target the very host pathways activated by vaccination. These immune evasion tactics blunt the effectiveness of immunization strategies and are impeding progress to control these infections throughout the world. Therefore, it is essential that M. tuberculosis immune-evasion related pathogen virulence strategies are considered to maximize the effectiveness of potential new treatments. In this review, we focus on how Mycobacterium tuberculosis infects antigen presenting cells and evades effective immune clearance by the adaptive response through i) manipulating antigen presentation ii) repressing T-cell activating co-stimulatory molecules, and iii) inducing ligands that drive T-cell exhaustion. In this context, we will examine the challenges that bacterial virulence strategies pose to developing new vaccines. We will then discuss new approaches that will help dissect M. tuberculosis immune evasion mechanisms and devise strategies to bypass them to promote long-term protection and prevent disease progression. Copyright © 2020 American Society for Microbiology.OBJECTIVE To evaluate if qualitative visual detection of pulsus paradoxus (PP) on the pulse oximeter plethysmograph can predict outcomes for children with moderate to severe respiratory distress in a paediatric emergency department (ED). DESIGN Prospective cohort study. SETTING Paediatric ED of a tertiary paediatrics hospital in Singapore. PATIENTS Children managed for moderate to severe wheezing in the resuscitation bay of the ED. INTERVENTIONS Patients were assessed for the presence of PP based on visual detection of oximeter plethysmograph before and after initial inhaled bronchodilator therapy. MAIN OUTCOME MEASURES These include the need for adjunct medications such as aminophylline or magnesium sulfate, the need for supplementary ventilation and the need for admission to the high dependency unit (HDU) or intensive care unit (ICU). RESULTS There were 285 patients included in the study, of whom 78 (27.4%) had PP at ED presentation. There were 40 (14.0%) who had PP after initial management. Children who had PP after initial management had significantly relative risks (RR) of requiring adjunct medications (RR 12.5, 95% CI 4.0 to 38.6), need for supplementary ventilation (RR 5.6, 95% CI 1.2 to 26.5) and admission to the HDU/ICU (RR 5.6, 95% CI 3.0 to 10.4). CONCLUSION Qualitative detection of PP on pulse oximetry can be used as a potential point-of-care tool to help in the assessment of response to initial treatment in paediatric patients with acute moderate to severe asthma exacerbations. Future studies are needed to assess and validate its role in guiding ED management of acute paediatric asthma. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.We aimed to evaluate a screening programme for infection in unaccompanied asylum seeking children and young people against national guidance and to described the rates of identified infection in the cohort. The audit was conducted by retrospective case note review of routinely collected, anonymised patient data from all UASC referred between January 2016 and December 2018 in two paediatric infectious diseases clinics.There were 252 individuals from 19 countries included in the study, of these 88% were male, and the median age was 17 years (range 11-18). Individuals from Afghanistan, Eritrea and Albania constituted the majority of those seen. Median time between arriving in the UK and infection screening was 6 months (IQR 4-10 months, data available on 197 UASC). There were 94% (238/252) of cases tested for tuberculosis (TB), of whom 23% (55/238) were positive, including three young people with TB disease. Of those tested for hepatitis B, 4.8% (10/210) were positive, 0.5% (1/121) were positive for hepatitis C and of 252 tested, none were positive for HIV. Of the 163 individuals who were tested for schistosomiasis, 27 were positive (16%).The majority of patients were appropriately tested for infections with a high rate of identification of treatable asymptomatic infection. WST-8 price Infections were of both individual and public health significance. Our findings of clinically significant rates of treatable infections in UASC highlight the importance of infection screening for all in this vulnerable patient group. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia. METHODS We performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system. RESULTS Patients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations.
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