Antimicrobial storage and antibiotic knowledge in the community: a cross-sectional pilot study in north-western Angola

Background - Antimicrobials are drugs that were once lifesavers and mainly curative. Nowadays their value is increasingly under pressure because of the fast and worldwide emergence of antimicrobial resistance, which, in low resources settings, frequently occurs in microorganisms that are likely to be transmitted in the community. Methods - A cross-sectional pilot study including 102 households within the 10th HDSS round in Dande, Bengo Province, Angola. Results - From the total 102 households piloted, 77.45% were urban (n = 79); the respondents were females in 56.44% (n = 57) and mean age was 39.70 (SD 15.35). Overall storage of antimicrobials was found in 55/102 (53.92%) of the households. More than 66% of the antimicrobials stored were prescribed by a health professional and the majority of antimicrobials were bought at pharmacies and at a street market. Penicillin and its derivates, antimalarial drugs and metronidazole are the most frequently antimicrobials stored. Households with female respondents reported to store more frequently any drugs at home (82.50%) (p = 0.002) and also more antimicrobials (64.91%; p = 0.016) as compared to households with male respondents. Reported use of antimicrobials was significantly higher in urban 60.76% (48/79) as compared to rural households 30.43% (7/23), (p = 0.010). Overall, 74/101 (73.26%) of respondents reported to have already heard about antibiotics. Among them, the common reasons for its use were cough and other respiratory symptoms, wounds, flu and body muscle pain, fever, bladder complaints, diarrhea and/or presumed typhoid fever. Nearly 40% (28/74) of the respondents thought that antibiotics should be stopped as soon as people dońt feel sick anymore. Conclusions - Community interventions for appropriate use of antibiotics should be designed with a special focus in women; through public awareness campaigns and improving access to reliable medical services. Drug prescribers are a keystone not only in adequate antimicrobial prescription but also adequate dispensing and strong advocates for the possible misconceptions on antimicrobial usage by laypeople.info:eu-repo/semantics/publishedVersio

Outbreak of Burkholderia cepacia bloodstream infections traced to the use of Ringer lactate solution as multiple-dose vial for catheter flushing, Phnom Penh, Cambodia

AbstractThe Burkholderia cepacia complex is a group of Gram-negative bacteria known as respiratory pathogens in cystic fibrosis patients, but also increasingly reported as a cause of healthcare associated infections. We describe an outbreak of B. cepacia bloodstream infections in a referral hospital in Phnom Penh, Cambodia. Over a 1.5-month period, blood cultures from eight adult patients grew B. cepacia. Bloodstream infection occurred after a median of 2.5 days of hospitalisation. Three patients died: 7, 10 and 17 days after blood cultures were sampled. As part of the outbreak investigation, patient files were reviewed and environmental sampling was performed. All patients had peripheral venous catheters that were flushed with Ringer lactate drawn from a 1 L bag, used as multiple-dose vial at the ward. Cultures of unopened Ringer lactate and disinfectants remained sterile but an in-use bag of Ringer lactate solution and the dispensing pin grew B. cepacia. The isolates from patients and flushing solution were identified as B. cepacia by recA gene sequence analysis, and random amplified polymorphic DNA typing confirmed clonal relatedness. The onset of the outbreak had coincided with the introduction of a dispensing pin with a screw fit that did not allow proper disinfection. Re-enforcement of aseptic procedures with sterile syringe and needle has ended the outbreak. Growth of B. cepacia should alert the possibility of healthcare associated infection also in tropical resource-limited settings. The use of multiple-dose vials should be avoided and newly introduced procedures should be assessed for infection control risks

ORegAnno: an open-access community-driven resource for regulatory annotation

ORegAnno is an open-source, open-access database and literature curation system for community-based annotation of experimentally identified DNA regulatory regions, transcription factor binding sites and regulatory variants. The current release comprises 30 145 records curated from 922 publications and describing regulatory sequences for over 3853 genes and 465 transcription factors from 19 species. A new feature called the ‘publication queue’ allows users to input relevant papers from scientific literature as targets for annotation. The queue contains 4438 gene regulation papers entered by experts and another 54 351 identified by text-mining methods. Users can enter or ‘check out’ papers from the queue for manual curation using a series of user-friendly annotation pages. A typical record entry consists of species, sequence type, sequence, target gene, binding factor, experimental outcome and one or more lines of experimental evidence. An evidence ontology was developed to describe and categorize these experiments. Records are cross-referenced to Ensembl or Entrez gene identifiers, PubMed and dbSNP and can be visualized in the Ensembl or UCSC genome browsers. All data are freely available through search pages, XML data dumps or web services at: http://www.oreganno.org

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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Corporeality, equality and education. A biopedagogical perspective

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“Ten Commandments” for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting

A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients’ compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically – but intelligently; know local susceptibility trends, and also surveillance limitations

A theoretical foundation for multi-scale regular vegetation patterns

Self-organized regular vegetation patterns are widespread and thought to mediate ecosystem functions such as productivity and robustness, but the mechanisms underlying their origin and maintenance remain disputed. Particularly controversial are landscapes of overdispersed (evenly spaced) elements, such as North American Mima mounds, Brazilian murundus, South African heuweltjies, and, famously, Namibian fairy circles. Two competing hypotheses are currently debated. On the one hand, models of scale-dependent feedbacks, whereby plants facilitate neighbours while competing with distant individuals, can reproduce various regular patterns identified in satellite imagery. Owing to deep theoretical roots and apparent generality, scale-dependent feedbacks are widely viewed as a unifying and near-universal principle of regular-pattern formation despite scant empirical evidence. On the other hand, many overdispersed vegetation patterns worldwide have been attributed to subterranean ecosystem engineers such as termites, ants, and rodents. Although potentially consistent with territorial competition, this interpretation has been challenged theoretically and empirically and (unlike scale-dependent feedbacks) lacks a unifying dynamical theory, fuelling scepticism about its plausibility and generality. Here we provide a general theoretical foundation for self-organization of social-insect colonies, validated using data from four continents, which demonstrates that intraspecific competition between territorial animals can generate the large-scale hexagonal regularity of these patterns. However, this mechanism is not mutually exclusive with scale-dependent feedbacks. Using Namib Desert fairy circles as a case study, we present field data showing that these landscapes exhibit multi-scale patterning-previously undocumented in this system-that cannot be explained by either mechanism in isolation. These multi-scale patterns and other emergent properties, such as enhanced resistance to and recovery from drought, instead arise from dynamic interactions in our theoretical framework, which couples both mechanisms. The potentially global extent of animal-induced regularity in vegetation-which can modulate other patterning processes in functionally important ways-emphasizes the need to integrate multiple mechanisms of ecological self-organization

Three-dimensional structure of a viral genome-delivery portal vertex.

DNA viruses such as bacteriophages and herpesviruses deliver their genome into and out of the capsid through large proteinaceous assemblies, known as portal proteins. Here, we report two snapshots of the dodecameric portal protein of bacteriophage P22. The 3.25-Å-resolution structure of the portal-protein core bound to 12 copies of gene product 4 (gp4) reveals a ~1.1-MDa assembly formed by 24 proteins. Unexpectedly, a lower-resolution structure of the full-length portal protein unveils the unique topology of the C-terminal domain, which forms a ~200-Å-long α-helical barrel. This domain inserts deeply into the virion and is highly conserved in the Podoviridae family. We propose that the barrel domain facilitates genome spooling onto the interior surface of the capsid during genome packaging and, in analogy to a rifle barrel, increases the accuracy of genome ejection into the host cell

Reverse Engineering the Yeast RNR1 Transcriptional Control System

Transcription is controlled by multi-protein complexes binding to short non-coding regions of genomic DNA. These complexes interact combinatorially. A major goal of modern biology is to provide simple models that predict this complex behavior. The yeast gene RNR1 is transcribed periodically during the cell cycle. Here, we present a pilot study to demonstrate a new method of deciphering the logic behind transcriptional regulation. We took regular samples from cell cycle synchronized cultures of Saccharomyces cerevisiae and extracted nuclear protein. We tested these samples to measure the amount of protein that bound to seven different 16 base pair sequences of DNA that have been previously identified as protein binding locations in the promoter of the RNR1 gene. These tests were performed using surface plasmon resonance. We found that the surface plasmon resonance signals showed significant variation throughout the cell cycle. We correlated the protein binding data with previously published mRNA expression data and interpreted this to show that transcription requires protein bound to a particular site and either five different sites or one additional sites. We conclude that this demonstrates the feasibility of this approach to decipher the combinatorial logic of transcription

Rosetta FlexPepDock ab-initio: Simultaneous Folding, Docking and Refinement of Peptides onto Their Receptors

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions