Airway response to respiratory syncytial virus has incidental antibacterial effects.

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children

Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated with the Airway Microbiota

Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria provoked a 3–5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory effects on DCs. Co-culture experiments found that Prevotella spp. were able to reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was observed on IL-23 and IL-10 production. This study demonstrates intrinsic differences in DC stimulating properties of bacteria associated with the airway microbiota

Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates

Contains fulltext : 97744.pdf (publisher's version ) (Open Access)BACKGROUND: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. RESULTS: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. CONCLUSIONS: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens

Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries:results of an internet-based global point prevalence survey

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux

Excessive substance use in bipolar disorder is associated with impaired functioning rather than clinical characteristics, a descriptive study

<p>Abstract</p> <p>Background</p> <p>There is a strong association between bipolar disorder (BD) and substance use disorder (SUD). The clinical and functional correlates of SUD in BD are still unclear and little is known about the role of excessive substance use that does not meet SUD criteria. Thus, the aims of the current study were to investigate lifetime rates of illicit substance use in BD relative to the normal population and if there are differences in clinical and functional features between BD patients with and without excessive substance use.</p> <p>Methods</p> <p>125 consecutively recruited BD in- and outpatients from the Oslo University Hospitals and 327 persons randomly drawn from the population in Oslo, Norway participated. Clinical and functional variables were assessed. Excessive substance use was defined as DSM-IV SUD and/or excessive use according to predefined criteria.</p> <p>Results</p> <p>The rate of lifetime illicit substance use was significantly higher among patients compared to the reference population (OR = 3.03, CI = 1.9-4.8, p < .001). Patients with excessive substance use (45% of total) had poorer educational level, occupational status, GAF-scores and medication compliance, with a trend towards higher suicidality rates, compared to patients without. There were no significant group differences in current symptom levels or disease course between groups.</p> <p>Conclusion</p> <p>The percentage of patients with BD that had tried illicit substances was significantly higher than in the normal population. BD patients with excessive substance use clearly had impaired functioning, but not a worse course of illness compared to patients without excessive substance use. An assessment of substance use beyond SUD criteria in BD is clinically relevant.</p

Multisensory games-based learning - lessons learnt from olfactory enhancement of a digital board game

Serious games are becoming an alternative educational method in a variety of fields because of their potential to improve the quality of learning experiences and to facilitate knowledge acquisition and content understanding. Moreover, entertainment-driven learners are more easily motivated to benefit from the learning process through meaningful activities defined in a game context. Interfacing educational computer games with multisensorial interfaces allows for a seamless integration between virtual and physical environments. Multisensorial cues can improve memory and attention and increase the cognitive and sensory-motor performance. Despite of the increasing knowledge in sensory processes, multisensory experiences and interactions in computer based instruction remain insufficiently explored and understood. In this paper, we present a multisensory educational game - Fragrance Channel - and we investigate how enabling olfaction can contribute to users' learning performance, engagement and quality of experience. We compare results obtained after experiencing Fragrance Channel in the presence and absence of olfactory feedback on both a mobile and a PC. A knowledge test administered before and immediately after showed that our proposed educational game led to an improvement of performance in all the explored conditions. Subjective measurements carried out after the olfactory experience showed that students enjoyed the scenario and appreciated it as being relevant.European Union’s Horizon 2020 Research and Innovation programm