Macrophages Are Required for Dendritic Cell Uptake of Respiratory Syncytial Virus from an Infected Epithelium

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

<p>Abstract</p> <p>Background</p> <p>Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields.</p> <p>Methods</p> <p>We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 μT-years), and less or little exposed shunting yard engineers (42.1 μT-years), train attendants (13.3 μT-years) and station masters (5.7 μT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models.</p> <p>Results</p> <p>For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants.Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 1.30 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 μT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction.</p> <p>Conclusion</p> <p>This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.</p

The month of July: an early experience with pandemic influenza A (H1N1) in adults with cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Pandemic Influenza A (H1N1) 2009 is a novel viral infection that emerged in March 2009. This is the first report addressing the clinical course of patients with cystic fibrosis (CF) and H1N1 infection.</p> <p>Methods</p> <p>All patients with an influenza-like illness (ILI) attending our adult centre during July 2009 were identified. Baseline respiratory function, nutritional status, approach to management and short-term clinical course were recorded.</p> <p>Results</p> <p>Most patients experienced a mild course and were able to be managed with antiviral agents as an outpatient. Robust infection control policies were implemented to limit transmission of H1N1 infection within our CF centre. Patients with severe lung disease, poor baseline nutritional reserve and presenting with more than 48 hours of ILI experienced a more severe course. Prompt antiviral therapy within the first 48 hours of illness may have been important in improving outcomes.</p> <p>Conclusions</p> <p>This observational study demonstrates that most adults with CF with H1N1 infection had mild clinical courses and recovered rapidly.</p

Evidence of Increased Muscle Atrophy and Impaired Quality of Life Parameters in Patients with Uremic Restless Legs Syndrome

BACKGROUND: Restless Legs Syndrome is a very common disorder in hemodialysis patients. Restless Legs Syndrome negatively affects quality of life; however it is not clear whether this is due to mental or physical parameters and whether an association exists between the syndrome and parameters affecting survival. METHOD#ENTITYSTARTX003BF;LOGY/PRINCIPAL FINDINGS: Using the Restless Legs Syndrome criteria and the presence of Periodic Limb Movements in Sleep (PLMS/h >15), 70 clinically stable hemodialysis patients were assessed and divided into the RLS (n = 30) and non-RLS (n = 40) groups. Physical performance was evaluated by a battery of tests: body composition by dual energy X ray absorptiometry, muscle size and composition by computer tomography, while depression symptoms, perception of sleep quality and quality of life were assessed through validated questionnaires. In this cross sectional analysis, the RLS group showed evidence of thigh muscle atrophy compared to the non-RLS group. Sleep quality and depression score were found to be significantly impaired in the RLS group. The mental component of the quality of life questionnaire appeared significantly diminished in the RLS group, reducing thus the overall quality of life score. In contrast, there were no significant differences between groups in any of the physical performance tests, body and muscle composition. CONCLUSIONS: The low level of quality of life reported by the HD patients with Restless Legs Syndrome seems to be due mainly to mental health and sleep related aspects. Increased evidence of muscle atrophy is also observed in the RLS group and possibly can be attributed to the lack of restorative sleep

Hepatitis a among men who have sex with men in Barcelona, 1989-2010: insufficient control and need for new approaches

<p>Abstract</p> <p>Background</p> <p>Men who have sex with men (MSM) are a known group at risk for hepatitis A and outbreaks among this group are frequent. In Barcelona, vaccination for MSM has been recommended since 1994. In 1998 a vaccination campaign among preadolescents was implemented and an immunization program in gay bathhouses began in 2004. Objective: to asses the incidence of hepatitis A in adults in Barcelona from 1989 to 2010 and to evaluate the outbreaks among MSM including all genotypes involved.</p> <p>Methods</p> <p>All cases of acute hepatitis A among young adults notified to the Public Health Agency of Barcelona from 1989 to 2010 were included for analyses. We calculated the annual incidence rate and the incidence ratio male-to-female (M:F) as a marker for MSM. Spearman's coefficient was used to evaluate trends. We also evaluated the outbreaks among MSM and compared their characteristics using Chi-squared and ANOVA test. Fragment amplification of the VP1/P2A region was used for genetic analysis.</p> <p>Results</p> <p>The median annual incidence for the period of study was 4.7/100000 among females and 11.7/100000 among males. The rate of hepatitis A for adult woman decreased over time (Spearman' coefficient = -0.63, <it>p </it>= 0.002), whereas there was no decrease for adult men (Spearman' coefficient = 0.097, <it>p </it>= 0.67). During the study period the M:F ratio increased (Spearman' coefficient = 0.73, <it>p </it>< 0.001).</p> <p>Three large outbreaks among MSM were detected. When comparing outbreaks, there was a decrease in the percentage of bathhouse users (from 47% to 19%, <it>p </it>= 0.0001) and sex workers (from 6.5% to 0%) while the percentage of HIV infected individuals did not change significantly (range: 21%-28%, <it>p </it>= 0.36). The isolated strains were closely related to those circulating in Europe.</p> <p>Conclusions</p> <p>Annual incidences remain high among MSM without tendency to decrease. More strategies which effectively reach the whole MSM community are needed.</p

Developing a minimum common dataset for hip fracture audit to help countries set up national audits that can support international comparisons

Aims The aim of this study was to explore current use of the Global Fragility Fracture Network (FFN) Minimum Common Dataset (MCD) within established national hip fracture registries, and to propose a revised MCD to enable international benchmarking for hip fracture care. Methods We compared all ten established national hip fracture registries: England, Wales, and Northern Ireland; Scotland; Australia and New Zealand; Republic of Ireland; Germany; the Netherlands; Sweden; Norway; Denmark; and Spain. We tabulated all questions included in each registry, and cross-referenced them against the 32 questions of the MCD dataset. Having identified those questions consistently used in the majority of national audits, and which additional fields were used less commonly, we then used consensus methods to establish a revised MCD. Results A total of 215 unique questions were used across the ten registries. Only 72 (34%) were used in more than one national audit, and only 32 (15%) by more than half of audits. Only one registry used all 32 questions from the 2014 MCD, and five questions were only collected by a single registry. Only 21 of the 32 questions in the MCD were used in the majority of national audits. Only three fields (anaesthetic grade, operation, and date/time of surgery) were used by all ten established audits. We presented these findings at the Asia-Pacific FFN meeting, and used an online questionnaire to capture feedback from expert clinicians from different countries. A draft revision of the MCD was then presented to all 95 nations represented at the Global FFN conference in September 2021, with online feedback again used to finalize the revised MCD. Conclusion The revised MCD will help aspirant nations establish new registry programmes, facilitate the integration of novel analytic techniques and greater multinational collaboration, and serve as an internationally-accepted standard for monitoring and improving hip fracture services

CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

<div><h3>Background</h3><p>TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).</p> <h3>Methodology and Principal Findings</h3><p>In the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n = 160), adalimumab (n = 56) or etanercept (n = 21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) <em>in silico</em> database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher’s exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR = 4.43, 95% CI: 1.99–10.09, p = 7.211×10⁻⁵) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29–8.99, p = 3.336×10⁻⁶). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR = 4.01, 95% CI: 1.92–8.49, p = 5.067×10⁻⁵).</p> <h3>Conclusion</h3><p>Genetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.</p> </div

Human 13N-ammonia PET studies: the importance of measuring 13N-ammonia metabolites in blood

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements