Social and structural determinants of injection drug use-associated bacterial and fungal infections: a qualitative systematic review and thematic synthesis

BACKGROUND AND AIMS: Injection drug use-associated bacterial and fungal infections are increasingly common, and social contexts shape individuals' injecting practices and treatment experiences. We sought to synthesize qualitative studies of social-structural factors influencing incidence and treatment of injecting-related infections. METHODS: We searched PubMed, EMBASE, Scopus, CINAHL, and PsycINFO from January 1, 2000, to February 18, 2021. Informed by Rhodes' "risk environment" framework, we performed thematic synthesis in three stages: (1) line-by-line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; (3) consolidating descriptive themes into conceptual categories to identify higher-order analytic themes. RESULTS: We screened 4,841 abstracts and included 26 qualitative studies on experiences of injecting-related bacterial and fungal infections. We identified six descriptive themes organized into two analytic themes. The first analytic theme, social production of risk, considered macro-environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health care policies and practices, leading to negative experiences that discourage access to care; and (4) restrictions on harm reduction programs, including structural barriers to effective service provision. The second analytic theme, practices of care among people who use drugs, addressed protective strategies people employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted-injecting and sharing sterile equipment; and (6) self-care, including vein health and self-treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g., HIV transmission). CONCLUSIONS: Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services, and harmful health care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community

Kill and cure: genomic phylogeny and bioactivity of Burkholderia gladioli bacteria capable of pathogenic and beneficial lifestyles.

Burkholderia gladioli is a bacterium with a broad ecology spanning disease in humans, animals and plants, but also encompassing multiple beneficial interactions. It is a plant pathogen, a toxin-producing food-poisoning agent, and causes lung infections in people with cystic fibrosis (CF). Contrasting beneficial traits include antifungal production exploited by insects to protect their eggs, plant protective abilities and antibiotic biosynthesis. We explored the genomic diversity and specialized metabolic potential of 206 B. gladioli strains, phylogenomically defining 5 clades. Historical disease pathovars (pv.) B. gladioli pv. allicola and B. gladioli pv. cocovenenans were distinct, while B. gladioli pv. gladioli and B. gladioli pv. agaricicola were indistinguishable; soft-rot disease and CF infection were conserved across all pathovars. Biosynthetic gene clusters (BGCs) for toxoflavin, caryoynencin and enacyloxin were dispersed across B. gladioli, but bongkrekic acid and gladiolin production were clade-specific. Strikingly, 13 % of CF infection strains characterized were bongkrekic acid-positive, uniquely linking this food-poisoning toxin to this aspect of B. gladioli disease. Mapping the population biology and metabolite production of B. gladioli has shed light on its diverse ecology, and by demonstrating that the antibiotic trimethoprim suppresses bongkrekic acid production, a potential therapeutic strategy to minimize poisoning risk in CF has been identified

Genomic Assemblies of Members of Burkholderia and Related Genera as a Resource for Natural Product Discovery.

The genomes of 450 members of Burkholderiaceae, isolated from clinical and environmental sources, were sequenced and assembled as a resource for genome mining. Genomic analysis of the collection has enabled the identification of multiple metabolites and their biosynthetic gene clusters, including the antibiotics gladiolin, icosalide A, enacyloxin, and cepacin A

Genome mining identifies cepacin as a plant-protective metabolite of the biopesticidal bacterium Burkholderia ambifaria.

Beneficial microorganisms are widely used in agriculture for control of plant pathogens, but a lack of efficacy and safety information has limited the exploitation of multiple promising biopesticides. We applied phylogeny-led genome mining, metabolite analyses and biological control assays to define the efficacy of Burkholderia ambifaria, a naturally beneficial bacterium with proven biocontrol properties but potential pathogenic risk. A panel of 64 B. ambifaria strains demonstrated significant antimicrobial activity against priority plant pathogens. Genome sequencing, specialized metabolite biosynthetic gene cluster mining and metabolite analysis revealed an armoury of known and unknown pathways within B. ambifaria. The biosynthetic gene cluster responsible for the production of the metabolite cepacin was identified and directly shown to mediate protection of germinating crops against Pythium damping-off disease. B. ambifaria maintained biopesticidal protection and overall fitness in the soil after deletion of its third replicon, a non-essential plasmid associated with virulence in Burkholderia cepacia complex bacteria. Removal of the third replicon reduced B. ambifaria persistence in a murine respiratory infection model. Here, we show that by using interdisciplinary phylogenomic, metabolomic and functional approaches, the mode of action of natural biological control agents related to pathogens can be systematically established to facilitate their future exploitation.A.J.M. is funded by a Biotechnology and Biological Sciences Research Council (BBSRC) South West doctoral training partnership award (BY1910 7007). E.M., G.L.C., T.R.C. and J.P. acknowledge additional support for genome mining from BBSRC award BB/L021692/1; C.J. and M.J. were funded by this award. M.J. is currently the recipient of a BBSRC Future Leader Fellowship (BB/R01212/1). The Bruker maXis II UHPLC-ESI-Q-TOF-MS system used in this research was funded by the BBSRC (BB/M017982/1). G.W. was supported by awards to E.M. from the Life Sciences Bridging Fund and Wellcome Trust Institutional Strategic Support Fund held at Cardiff University. T.R.C. and M.J.B. acknowledge funding support from the Medical Research Council’s Cloud Infrastructure for Microbial Bioinformatics (MR/L015080/1), which provided the computational resources to undertake the analyses for this work. D.R.N. and A.E.G. acknowledge funding from a Wellcome Trust and Royal Society Sir Henry Dale Fellowship awarded to D.R.N. (grant number 204457/Z/16/Z). G.L.C. is the recipient of a Wolfson Research Merit Award from the Royal Society (WM130033)

Two close large quasar groups of size ∼ 350 Mpc at

The Clowes & Campusano large quasar group (LQG) at inline image has been re-examined using the quasar data from the DR7QSO catalogue of the Sloan Digital Sky Survey. In the 1991 discovery, the LQG impinged on the northern, southern and eastern limits of the survey. In the DR7QSO data, the western, northern and southern boundaries of the LQG remain essentially the same, but an extension eastwards of ∼2° is indicated. In the DR7QSO data, the LQG has 34 members, with inline image. A new group of 38 members is indicated at inline image and within ∼2bsl000640 of the Clowes & Campusano LQG. The characteristic sizes of these two LQGs, ∼350–400 Mpc, appear to be only marginally consistent with the scale of homogeneity in the concordance cosmology. In addition to their intrinsic interest, these two LQGs provide locations in which to investigate early large-scale structure in galaxies and to identify high-z clusters. A method is presented for assessing the statistical significance and overdensity of groups found by linkage of points

Social and structural determinants of injection drug use-associated bacterial and fungal infections: A qualitative systematic review and thematic synthesis

BACKGROUND AND AIMS: Injection drug use-associated bacterial and fungal infections are increasingly common, and social contexts shape individuals' injecting practices and treatment experiences. We sought to synthesize qualitative studies of social-structural factors influencing incidence and treatment of injecting-related infections. METHODS: We searched PubMed, EMBASE, Scopus, CINAHL and PsycINFO from 1 January 2000 to 18 February 2021. Informed by Rhodes' 'risk environment' framework, we performed thematic synthesis in three stages: (1) line-by-line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; and (3) consolidating descriptive themes into conceptual categories to identify higher-order analytical themes. RESULTS: We screened 4841 abstracts and included 26 qualitative studies on experiences of injecting-related bacterial and fungal infections. We identified six descriptive themes organized into two analytical themes. The first analytical theme, social production of risk, considered macro-environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health-care policies and practices, leading to negative experiences that discourage access to care; and (4) restrictions on harm reduction programmes, including structural barriers to effective service provision. The second analytical theme, practices of care among people who use drugs, addressed protective strategies that people employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted-injecting and sharing sterile equipment; and (6) self-care, including vein health and self-treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g. HIV transmission). CONCLUSIONS: Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services and harmful health-care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community

A structure in the early Universe at z 1.3 that exceeds the homogeneity scale of the R-W concordance cosmology

A Large Quasar Group (LQG) of particularly large size and high membership has been identified in the DR7QSO catalogue of the Sloan Digital Sky Survey. It has characteristic size (volume^1/3) ~ 500 Mpc (proper size, present epoch), longest dimension ~ 1240 Mpc, membership of 73 quasars, and mean redshift = 1.27. In terms of both size and membership it is the most extreme LQG found in the DR7QSO catalogue for the redshift range 1.0 = 1.28, which is itself one of the more extreme examples. Their boundaries approach to within ~ 2 deg (~ 140 Mpc projected). This new, huge LQG appears to be the largest structure currently known in the early universe. Its size suggests incompatibility with the Yadav et al. scale of homogeneity for the concordance cosmology, and thus challenges the assumption of the cosmological principle

Using arterial spin labelling to investigate spontaneous and evoked ongoing musculoskeletal pain

Clinical pain is difficult to study using standard Blood Oxy-genation Level Dependent (BOLD) magnetic resonance imaging because it is often ongoing and, if evoked, it is associated with stimulus-correlated motion. Arterial spin labelling (ASL) offers an attractive alternative. This study used arm repositioning to evoke clinically-relevant musculoskeletal pain in patients with shoulder impingement syndrome. Fifty-five patients were scanned using a multi post-labelling delay pseudo-continuous ASL (pCASL) sequence, first with both arms along the body and then with the affected arm raised into a painful position. Twenty healthy volunteers were scanned as a control group. Arm repositioning resulted in increased perfusion in brain regions involved in sensory processing and movement integration, such as the contralateral primary motor and primary somatosensory cortex, mid- and posterior cingulate cortex, and, bilaterally, in the insular cortex/operculum, putamen, thalamus, midbrain and cerebellum. Perfusion in the thalamus, midbrain and cerebellum was larger in the patient group. Results of a post hoc analysis suggested that the observed perfusion changes were related to pain rather than arm repositioning. This study showed that ASL can be useful in research on clinical ongoing musculoskeletal pain but the technique is not sensitive enough to detect small differences in perfusion

Identification of the Antibacterial Compound Produced by the Marine Epiphytic Bacterium Pseudovibrio sp. D323 and Related Sponge-Associated Bacteria

Surface-associated marine bacteria often produce secondary metabolites with antagonistic activities. In this study, tropodithietic acid (TDA) was identified to be responsible for the antibacterial activity of the marine epiphytic bacterium Pseudovibrio sp. D323 and related strains. Phenol was also produced by these bacteria but was not directly related to the antibacterial activity. TDA was shown to effectively inhibit a range of marine bacteria from various phylogenetic groups. However TDA-producers themselves were resistant and are likely to possess resistance mechanism preventing autoinhibition. We propose that TDA in isolate D323 and related eukaryote-associated bacteria plays a role in defending the host organism against unwanted microbial colonisation and, possibly, bacterial pathogens