Inflammatory Cytokine Profiles During Exercise in Obese, Diabetic, and Healthy Children

Objective: Modulation of inflammatory status is considered a key component of the overall health effects of exercise. This may be especially relevant in children with obesity (Ob) or type 1 diabetes (T1DM), in which an imbalance between pro- and anti-inflammatory mediators could accelerate onset and progression of cardiovascular complications. To date, exercise-induced alterations in immuno-modulatory mediators in Ob and T1DM children remain largely unknown

Quantifying the importance of plastic pollution for the dissemination of human pathogens: The challenges of choosing an appropriate 'control' material

Discarded plastic wastes in the environment are serious challenges for sustainable waste management and for the delivery of environmental and public health. Plastics in the environment become rapidly colonised by microbial biofilm, and importantly this so-called ‘plastisphere’ can also support, or even enrich human pathogens. The plastisphere provides a protective environment and could facilitate the increased survival, transport and dissemination of human pathogens and thus increase the likelihood of pathogens coming into contact with humans, e.g., through direct exposure at beaches or bathing waters. However, much of our understanding about the relative risks associated with human pathogens colonising environmental plastic pollution has been inferred from taxonomic identification of pathogens in the plastisphere, or laboratory experiments on the relative behaviour of plastics colonised by human pathogens. There is, therefore, a pressing need to understand whether plastics play a greater role in promoting the survival and dispersal of human pathogens within the environment compared to other substrates (either natural materials or other pollutants). In this paper, we consider all published studies that have detected human pathogenic bacteria on the surfaces of environmental plastic pollution and critically discuss the challenges of selecting an appropriate control material for plastisphere experiments. Whilst it is clear there is no ‘perfect’ control material for all plastisphere studies, understanding the context-specific role plastics play compared to other substrates for transferring human pathogens through the environment is important for quantifying the potential risk that colonised plastic pollution may have for environmental and public health

Clinically important E. coli strains can persist, and retain their pathogenicity, on environmental plastic and fabric waste

Plastic waste is ubiquitous in the environment and there are increasing reports of such waste being colonised by human pathogens. However, the ability of pathogens to persist on plastics for long periods, and the risk that they pose to human health, is unknown. Here, under simulated environmental conditions, we aimed to determine if pathogenic bacteria can retain their virulence following a prolonged period on plastic. Using antibiotic selection and luciferase expression for quantification, we show that clinically important strains of E. coli can survive on plastic for at least 28-days. Importantly, these pathogens also retained their virulence (determined by using a Galleria mellonella model as a surrogate for human infection) and in some cases, had enhanced virulence following their recovery from the plastisphere. This indicates that plastics in the environment can act as reservoirs for human pathogens and could facilitate their persistence for extended periods of time. Most importantly human pathogens in the plastisphere are capable of retaining their pathogenicity. Pathogens colonising environmental plastic waste therefore pose a heightened public health risk, particularly in areas where people are exposed to pollution

From wastewater discharge to the beach: Survival of human pathogens bound to microplastics during transfer through the freshwater-marine continuum

Large quantities of microplastics are regularly discharged from wastewater treatment plants (WWTPs) into the aquatic environment. Once released, these plastics can rapidly become colonised by microbial biofilm, forming distinct plastisphere communities which may include potential pathogens. We hypothesised that the protective environment afforded by the plastisphere would facilitate the survival of potential pathogens during transitions between downstream environmental matrices and thus increase persistence and the potential for environmental dissemination of pathogens. The survival of Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa colonising polyethylene or glass particles has been quantified in mesocosm incubation experiments designed to simulate, (1) the direct release of microplastics from WWTPs into freshwater and seawater environments; and (2) the movement of microplastics downstream following discharge from the WWTP through the river-estuary-marine-beach continuum. Culturable E. coli, E. faecalis and P. aeruginosa were successfully able to survive and persist on particles whether they remained in one environmental matrix or transitioned between different environmental matrices. All three bacteria were still detectable on both microplastic and glass particles after 25 days, with higher concentrations on microplastic compared to glass particles; however, there were no differences in bacterial die-off rates between the two materials. This potential for environmental survival of pathogens in the plastisphere could facilitate their transition into places where human exposure is greater (e.g., bathing waters and beach environments). Therefore, risks associated with pathogen-microplastic co-pollutants in the environment, emphasises the urgency for updated regulations on wastewater discharge and the management of microplastic generation and release

Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance

Trypanosoma brucei rhodesiense (Tbr) and T. b. gambiense (Tbg), causative agents of Human African Trypanosomiasis (sleeping sickness) in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs), components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA) protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR). HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb), a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR functio

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

Sewage-associated plastic waste washed up on beaches can act as a reservoir for faecal bacteria, potential human pathogens, and genes for antimicrobial resistance

Sewage-associated plastic wastes, such as wet wipes and cotton bud sticks, commonly wash up on beaches; however, it is unclear whether this represents a public health risk. In this study, sewage-associated plastic waste, and naturally occurring substrates (seaweed and sand), were collected from ten beaches along the Firth of Forth estuary (Scotland, UK) and analysed using selective media for the faecal indicator organisms (FIOs) E. coli and intestinal enterococci (IE), and potential human pathogens (Vibrio spp.). Minimum inhibitory concentration (MIC) analysis was used to determine antibiotic resistance in selected strains. FIOs and Vibrio were more often associated with wet wipes and cotton bud sticks than with seaweed, and there was evidence of resistance to several antibiotics. This work demonstrates that plastics associated with sewage pollution can facilitate the survival and dissemination of FIOs and Vibrio and thus, could present an as yet unquantified potential risk to human health at the beach

Enduring pathogenicity of African strains of Salmonella on plastics and glass in simulated peri-urban environmental waste piles

In low- and middle-income countries, plastic has become a major constituent of landfills and urban dump sites. Environmental plastic pollution can also provide a novel surface for the formation of microbial biofilm, which often includes pathogenic bacteria and viruses. Here, under conditions simulating a peri-urban waste pile typical of an African informal settlement, we aimed to determine if pathogenic Salmonella spp. can retain their virulence following a prolonged period of desiccation on the surfaces of environmental plastic and glass. We show that clinically (and environmentally) relevant strains of Salmonella including S. Enteritidis, S. Typhimurium and S. Typhi can persist on plastic and glass for at least 28-days and that temperature (which increases with the depth of an urban waste pile) is a key determinant of this survival. All three strains of Salmonella retained their pathogenicity (determined by using a Galleria mellonella model of infection) following their recovery from the plastisphere indicating that plastics in the environment can act as reservoirs for human pathogens and could facilitate their persistence for extended periods of time. Pathogens colonising environmental plastic waste therefore pose a heightened public health risk, particularly in areas where people are frequently exposed to plastic pollution

Integrating Murine Gene Expression Studies to Understand Obstructive Lung Disease due to Chronic Inhaled Endotoxin

Rationale: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. Methods: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. Results: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. Conclusions: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observed. The endotoxin component of tobacco smoke may play an important role in disease development