Knowlesi malaria in Vietnam

The simian malaria parasite Plasmodium knowlesi is transmitted in the forests of Southeast Asia. Symptomatic zoonotic knowlesi malaria in humans is widespread in the region and is associated with a history of spending time in the jungle. However, there are many settings where knowlesi transmission to humans would be expected but is not found. A recent report on the Ra-glai population of southern central Vietnam is taken as an example to help explain why this may be so

Implicating Receptor Activator of NF-κB (RANK)/RANK Ligand Signalling in Microglial Responses to Toll-Like Receptor Stimuli

Inflammation in the perinatal brain caused by maternal or intrauterine fetal infection is now well established as an important contributor to the development of perinatal brain injury. Exposure to inflammatory products can impair perinatal brain development and act as a risk factor for neurological dysfunction, cognitive disorders, cerebral palsy, or preterm birth. Pre-exposure to inflammation significantly exacerbates brain injury caused by hypoxic/ischaemic insult. Tumour necrosis factor (TNF) is a family of cytokines largely involved in inflammation signalling. In our previous study, we identified the importance of TNF-related apoptosis-inducing ligand (TRAIL) signalling in the development of perinatal brain injury. We observed a significant increase in the expression levels of a soluble decoy receptor for TRAIL, osteoprotegerin (OPG). Besides TRAIL, OPG is able to bind the receptor activator of the NF-&amp;#x03BA;B (RANK) ligand (RANKL) and inhibit its signalling. The function of the RANK/RANKL/OPG system in the brain has not come under much scrutiny. The aim of this research study was to elucidate the role of RANK, RANKL, and OPG in microglial responses to the proinflammatory stimuli lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (Poly I:C). Here, we show that RANK signalling is important for regulating the activation of the BV2 microglial cell line. We found that LPS treatment causes a significant decrease in the expression of RANK in the BV2 cell line while significantly increasing the expression of OPG, Toll-like receptor (TLR)3, and the adaptor proteins MyD88 and TRIF. We found that pretreatment of BV2 cells with RANKL for 24 h before the LPS or Poly I:C exposure decreases the expression of inflammatory markers such as inducible nitric oxide synthase and cyclooxygenase. This is accompanied by a decreased expression of the TLR adaptor proteins MyD88 and TRIF, which we observed after RANKL treatment. Similar results were obtained in our experiments with primary mouse microglia. Using recently developed CRISPR/Cas9 technology, we generated a BV2 cell line lacking RANK (RANK&lt;sup&gt;-/-&lt;/sup&gt; BV2). We showed that most effects of RANKL pretreatment were abolished, thereby proving the specificity of this effect. Taken together, these findings suggest that RANK signalling is important for modulating the inflammatory activation of microglial cells to a moderate level, and that RANK attenuates TLR3/TLR4 signalling.</jats:p

Antimicrobial resistance and the environment : assessment of advances, gaps and recommendations for agriculture, aquaculture and pharmaceutical manufacturing

A roundtable discussion held at the fourth International Symposium on the Environmental Dimension of Antibiotic Resistance (EDAR4) considered key issues concerning the impact on the environment of antibiotic use in agriculture and aquaculture, and emissions from antibiotic manufacturing. The critical control points for reducing emissions of antibiotics from agriculture are antibiotic stewardship and the pre-treatment of manure and sludge to abate antibiotic-resistant bacteria. Antibiotics are sometimes added to fish and shellfish production sites via the feed, representing a direct route of contamination of the aquatic environment. Vaccination reduces the need for antibiotic use in high value (e.g. salmon) production systems. Consumer and regulatory pressure will over time contribute to reducing the emission of very high concentrations of antibiotics from manufacturing. Research priorities include the development of technologies, practices and incentives that will allow effective reduction in antibiotic use, together with evidence-based standards for antibiotic residues in effluents. All relevant stakeholders need to be aware of the threat of antimicrobial resistance and apply best practice in agriculture, aquaculture and pharmaceutical manufacturing in order to mitigate antibiotic resistance development. Research and policy development on antimicrobial resistance mitigation must be cognizant of the varied challenges facing high and low income countries.Peer reviewe

Comparative Testing Report on the Detection and Quantification of Maize Event MON 810 - Comparative testing round: ILC-CRL-GMFF-CT-02/10

In the frame of Regulation (EC) No 882/2004, the European Union Reference Laboratory for Genetically Modified Food and Feed has the duty to organise comparative testing rounds and to ensure an appropriate follow-up of these activities. This report describes the outcome of the second comparative testing round ILC-CRL-GMFF-CT-02/10. Participants had to determine the GM content in two test items denoted maize powder levels 1 and 2, containing different GM percentages of maize event MON 810. This comparative testing round was organised in collaboration with the Reference Materials Unit and the Food Safety and Quality Unit of the Institute for Reference Materials and Measurements (Geel, BE). The maize event MON 810 test items were produced by the Reference Materials Unit. The Food Safety and Quality Unit managed the on-line registration and submission of results. A total of 136 laboratories were invited to participate in ILC-CRL-GMFF-CT-02/10. Six National Reference Laboratories declined participation, of which two were no longer a National Reference Laboratory. Ninety laboratories from 41 countries returned results, of which 65 were National Reference Laboratories, six were members of the European Network of GMO Laboratories only and 19 were laboratories from third countries. Two National Reference Laboratories, two Official control laboratories and nine laboratories from a third country did not submit any results. Participants could report the results of the exercise either in mass/mass % or in copy/copy %. The outcome of this second comparative testing round was in general positive, with 82-100 % of participants gaining a z-score in the range of -2 to +2 for both maize powder levels 1 and 2 regardless of the calibration method, the measurement unit and the approach used for calculating the z-score.JRC.I.3-Molecular Biology and Genomic

De consultatie-liaisonpsychiatrie in de Belgische ziekenhuizen van de eenentwintigste eeuw : quo vadis?

In een tijd waarin de geneeskunde zich uitsplitst in een groeiend aantal specialismen, subspecialismen en superspecialismen is er in de algemene en de universitaire ziekenhuizen een toenemende nood aan multidisciplinaire samenwerking. Deze vorm van samenwerking is nodig om hoogstaande holistische zorg te blijven verlenen aan de patiënt als centrale figuur in het zorgproces. De technologische mogelijkheden in de geneeskundige zorg nemen toe, maar er is een belangrijke comorbiditeit tussen de medische aandoeningen. De consultatie-liaisonpsychiatrie (CLP) is een van de disciplines die hierop inspeelt. Deze discipline focust vanuit een multidisciplinaire en integrale zorgvisie op de psychiatrische diagnostiek en behandeling van patiënten met psychiatrische en somatische comorbiditeit die hiervoor behandeld en opgevolgd worden in een algemeen ziekenhuis. Dit artikel wil een overzicht geven van de functies van de CLP zowel binnen als buiten het ziekenhuis en licht het historische en huidige Belgische beleid en de wetgeving ter zake toe. Er worden ook aanbevelingen geformuleerd voor de toekomst en men pleit voor de implementatie van de CLP als een volwaardige en structurele klinische activiteit en opdracht in de algemene ziekenhuizen

Plasmodium knowlesi malaria in Vietnam: some clarifications

A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed

Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD

Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD

Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistanc

This is the final version of the article. Available from NIEHS via the DOI in this record.Open access journalBACKGROUND: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. OBJECTIVE: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. METHODS: The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. DISCUSSION: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways. CONCLUSIONS: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.This manuscript was conceived at a workshop (Antimicrobial Resistance in the Environment: Assessing and Managing Effects of Anthropogenic Activities) held 4–8 March 2012 in Montebello, Québec, Canada. The workshop was sponsored by the Canadian Society of Microbiologists, with financial support from AstraZeneca Ltd.; Pfizer Animal Health; F. Hoffman-La Roche Ltd.; GlaxoSmithKline; Unilever; Huvepharma; the American Cleaning Institute; the Canadian Animal Health Institute; the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety; Health Canada; and the Public Health Agency of Canada