50 research outputs found

    USE OF NOVEL PSYCHOACTIVE SUBSTANCES (NPS) OF NATURAL ORIGIN: AN INTERNATIONAL SURVEY

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    Aim NPS recreational use are mostly derived and modified from constituents of natural origin. Here we investigated the motivation of natural NPS use, perception of potential associated health risks and demographic factors associated with natural NPS use. Methodology The Bristol Online Survey was in English and advertised on the drug forum Bluelight and social media Facebook pages and via University email between 1 July and 17 November 2018 (812 responses; 458 NPS users). This pharmacoepidemiologic study was evaluated using SPSS software (IBM SPSS Statistics version 24;MacOS Sierra 10.12.3). Results The main motivation (67%) for natural NPS use was curiosity to ‘’experience something new and different’’ with a low perception of health risk (85%). The preferred natural NPS was magic mushrooms (psilocybin, 95%) often in combination with cannabis (63%). Gender, living area, educational background, smoking frequency and employment significantly affected (P<0.001) natural NPS use. Male respondents, residents of suburban and rural areas, smokers and respondents with low educational level represented the majority of natural NPS users as well as the employed, the unable to work and retired groups. Similarly, sexual orientation significantly affected (p<0.05) natural NPS use. Conclusion Users’ low perception of natural NPS safety profile and the fact that natural NPS use correlates with a lower level of education, indicates a need for enhanced statutory targeted prevention interventions in schools. Many users (67%) reported natural NPS make them happier and more optimistic about life emphasizing the need to study the potential application of these substances in appropriate clinical settings for therapeutic purposes in mental health.Peer reviewe

    IDOMAL: an ontology for malaria

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    <p>Abstract</p> <p>Background</p> <p>Ontologies are rapidly becoming a necessity for the design of efficient information technology tools, especially databases, because they permit the organization of stored data using logical rules and defined terms that are understood by both humans and machines. This has as consequence both an enhanced usage and interoperability of databases and related resources. It is hoped that IDOMAL, the ontology of malaria will prove a valuable instrument when implemented in both malaria research and control measures.</p> <p>Methods</p> <p>The OBOEdit2 software was used for the construction of the ontology. IDOMAL is based on the Basic Formal Ontology (BFO) and follows the rules set by the OBO Foundry consortium.</p> <p>Results</p> <p>The first version of the malaria ontology covers both clinical and epidemiological aspects of the disease, as well as disease and vector biology. IDOMAL is meant to later become the nucleation site for a much larger ontology of vector borne diseases, which will itself be an extension of a large ontology of infectious diseases (IDO). The latter is currently being developed in the frame of a large international collaborative effort.</p> <p>Conclusions</p> <p>IDOMAL, already freely available in its first version, will form part of a suite of ontologies that will be used to drive IT tools and databases specifically constructed to help control malaria and, later, other vector-borne diseases. This suite already consists of the ontology described here as well as the one on insecticide resistance that has been available for some time. Additional components are being developed and introduced into IDOMAL.</p

    Pseudomonas aeruginosa Cystic Fibrosis isolates of similar RAPD genotype exhibit diversity in biofilm forming ability in vitro

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    <p>Abstract</p> <p>Background</p> <p><it>Pseudomonas aeruginosa </it>is considered to grow in a biofilm in cystic fibrosis (CF) chronic lung infections. Bacterial cell motility is one of the main factors that have been connected with <it>P. aeruginosa </it>adherence to both biotic and abiotic surfaces. In this investigation, we employed molecular and microscopic methods to determine the presence or absence of motility in <it>P. aeruginosa </it>CF isolates, and statistically correlated this with their biofilm forming ability <it>in vitro</it>.</p> <p>Results</p> <p>Our investigations revealed a wide diversity in the production, architecture and control of biofilm formation. Of 96 isolates, 49% possessed swimming motility, 27% twitching and 52% swarming motility, while 47% were non-motile. Microtitre plate assays for biofilm formation showed a range of biofilm formation ability from biofilm deficient phenotypes to those that formed very thick biofilms. A comparison of the motility and adherence properties of individual strains demonstrated that the presence of swimming and twitching motility positively affected biofilm biomass. Crucially, however, motility was not an absolute requirement for biofilm formation, as 30 non-motile isolates actually formed thick biofilms, and three motile isolates that had both flagella and type IV pili attached only weakly. In addition, CLSM analysis showed that biofilm-forming strains of <it>P. aeruginosa </it>were in fact capable of entrapping non-biofilm forming strains, such that these 'non-biofilm forming' cells could be observed as part of the mature biofilm architecture.</p> <p>Conclusions</p> <p>Clinical isolates that do not produce biofilms in the laboratory must have the ability to survive in the patient lung. We propose that a synergy exists between isolates <it>in vivo</it>, which allows "non biofilm-forming" isolates to be incorporated into the biofilm. Therefore, there is the potential for strains that are apparently non-biofilm forming <it>in vitro </it>to participate in biofilm-mediated pathogenesis in the CF lung.</p

    Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage.

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    Pore forming proteins such as those belonging to the membrane attack/perforin (MACPF) family have important functions in many organisms. Of the five MACPF proteins found in Plasmodium parasites, three have functions in cell passage and one in host cell egress. Here we report an analysis of the perforin-like protein 4, PPLP4, in the rodent parasite Plasmodium berghei. We found that the protein is expressed only in the ookinete, the invasive stage of the parasite formed in the mosquito midgut. Transcriptional analysis revealed that expression of the pplp4 gene commences during ookinete development. The protein was detected in retorts and mature ookinetes. Using two antibodies, the protein was found localized in a dotted pattern, and 3-D SIM super-resolution microcopy revealed the protein in the periphery of the cell. Analysis of a C-terminal mCherry fusion of the protein however showed mainly cytoplasmic label. A pplp4 null mutant formed motile ookinetes, but these were unable to invade and traverse the midgut epithelium resulting in severely impaired oocyst formation and no transmission to naïve mice. However, when in vitro cultured ookinetes were injected into the thorax of the mosquito, thus by-passing midgut passage, sporozoites were formed and the mutant parasites were able to infect naïve mice. Taken together, our data show that PPLP4 is required only for ookinete invasion of the mosquito midgut. Thus PPLP4 has a similar role to the previously studied PPLP3 and PPLP5, raising the question why three proteins with MACPF domains are needed for invasion by the ookinete of the mosquito midgut epithelium

    Egress-related osmiophilic bodies

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    © 2014 John Wiley & Sons Ltd. Summary: Gametogenesis is the earliest event after uptake of malaria parasites by the mosquito vector, with a decisive impact on colonization of the mosquito midgut. This process is triggered by a drop in temperature and contact with mosquito molecules. In a few minutes, male and female gametocytes escape from the host erythrocyte by rupturing the parasitophorous vacuole and the erythrocyte membranes. Electron-dense, oval-shaped organelles, the osmiophilic bodies (OB), have been implicated in the egress of female gametocytes. By comparative electron microscopy and electron tomography analyses combined with immunolocalization experiments, we here define the morphological features distinctive of male secretory organelles, hereafter named MOB (male osmiophilic bodies). These organelles appear as club-shaped, electron-dense vesicles, smaller than female OB. We found that a drop in temperature triggers MOB clustering, independently of exposure to other stimuli. MDV1/PEG3, a protein associated with OB in Plasmodium berghei females, localizes to both non-clustered and clustered MOB, suggesting that clustering precedes vesicle discharge. A P.berghei mutant lacking the OB-resident female-specific protein Pbg377 displays a dramatic reduction in size of the OB, accompanied by a delay in female gamete egress efficiency, while female gamete fertility is not affected. Immunolocalization experiments indicated that MDV1/PEG3 is still recruited to OB-remnant structures

    Disinfection of Ocular Cells and Tissues by Atmospheric-Pressure Cold Plasma

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    Background: Low temperature plasmas have been proposed in medicine as agents for tissue disinfection and have received increasing attention due to the frequency of bacterial resistance to antibiotics. This study explored whether atmospheric-pressure cold plasma (APCP) generated by a new portable device that ionizes a flow of helium gas can inactivate ocular pathogens without causing significant tissue damage. Methodology and Principal Findings: We tested the APCP effects on cultured Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes simplex virus-1, ocular cells (conjunctival fibroblasts and keratocytes) and ex-vivo corneas. Exposure to APCP for 0.5 to 5 minutes significantly reduced microbial viability (colony-forming units) but not human cell viability (MTT assay, FACS and Tunel analysis) or the number of HSV-1 plaque-forming units. Increased levels of intracellular reactive oxygen species (ROS) in exposed microorganisms and cells were found using a FACS-activated 2',7'-dichlorofluorescein diacetate probe. Immunoassays demonstrated no induction of thymine dimers in cell cultures and corneal tissues. A transient increased expression of 8-OHdG, genes and proteins related to oxidative stress (OGG1, GPX, NFE2L2) was determined in ocular cells and corneas by HPLC, qRT-PCR and Western blot analysis. Conclusions: A short application of APCP appears to be an efficient and rapid ocular disinfectant for bacteria and fungi without significant damage on ocular cells and tissues, although the treatment of conjunctival fibroblasts and keratocytes caused a time-restricted generation of intracellular ROS and oxidative stress-related responses

    Analysis of the phenotypic properties relevant to biofilm production by Pseudomonas aeruginosa cystic fibrosis isolates

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    EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Use of Novel Psychoactive Substances (NPSs) of Natural Origin in the United Kingdom Population 2022

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    Introduction: In the last decade, there has been an emerging threat to public health due to the increase of recreational use of novel psychoactive substances (NPSs) that are mostly derived or modified from natural products. There is an urgent need for regulatory authorities, governments and scientific experts to tackle this issue. Objectives: The aim of this pharmacoepidemiological study was to investigate in the UK population the use of natural NPSs and the perception of potential associated health risks. Methods: The Bristol Online Survey was distributed on the Bluelight drug forum, social media pages and via University emails during 1 July and 17 November 2018. For the data analysis, the SPSS software was used (IBM SPSS version 26). Results: 207 UK responses were received from which 76 (36.7%) were users. The main motivations for natural NPSs use were “to experience something new and different” (70.1%) and “to fight depression/anxiety symptoms” (53.2%); 90% of users reported satisfaction after the use of natural NPSs. The most preferred natural NPS was magic mushrooms (psilocybin, 92%) often combined with cannabis (69%); with the most favourable place for taking them being outdoors in nature (67%). More than half of the users (56.6%) have stopped using natural NPSs in the past; one out of two users stated that they could not function normally throughout the day whilst taking natural NPSs. The majority (67.5%) believed that there is no risk or just a low risk by consuming their favourite natural NPSs when only 19 % stated that there is medium or high risk. Gender, age, employment, smoking frequency and religion significantly affected (P<0.001) natural NPSs use. Male respondents, middle-aged, habitual smokers, atheists and agnostics but also frequent alcohol consumers represented the majority of natural NPSs users as well as the employed, the unable to work (due to disability/accident) and retired groups. Conclusion: UK users’ low perception of natural NPSs safety profile and intoxication risks indicates a need for enhanced prevention interventions through education and drug policy updates.Peer reviewe
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