The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.

Chicken avidin and bacterial streptavidin, (strept)avidin, are proteins widely utilized in a number of applications in life science, ranging from purification and labeling techniques to diagnostics, and from targeted drug delivery to nanotechnology. (Strept)avidin-biotin technology relies on the extremely tight and specific affinity between (strept)avidin and biotin (dissociation constant, K(d) approximately 10(-14)-10(-16) M). (Strept)avidins are also exceptionally stable proteins. To study their ligand binding and stability characteristics, the two proteins have been extensively modified both chemically and genetically. There are excellent accounts of this technology and chemically modified (strept)avidins, but no comprehensive reviews exist concerning genetically engineered (strept)avidins. To fill this gap, we here go through the genetically engineered (strept)avidins, summarizing how these constructs were designed and how they have improved our understanding of the structural and functional characteristics of these proteins, and the benefits they have provided for (strept)avidin-biotin technology.

As the incidence of immune-mediated diseases has increased rapidly in developed societies, there is an unmet need for novel prophylactic practices to fight against these maladies. This study is the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children. We analyzed changes in the skin and gut microbiota and blood immune markers of children during a 28-day biodiversity intervention. Children in standard urban and nature-oriented daycare centers were analyzed for comparison. The intervention diversified both the environmental and skin Gammaproteobacterial communities, which, in turn, were associated with increases in plasma TGF-β1 levels and the proportion of regulatory T cells. The plasma IL-10:IL-17A ratio increased among intervention children during the trial. Our findings suggest that biodiversity intervention enhances immunoregulatory pathways and provide an incentive for future prophylactic approaches to reduce the risk of immune-mediated diseases in urban societies.

Fast, robust, and affordable antimicrobial susceptibility testing (AST) is required, as roughly 50% of antibiotic treatments are started with wrong antibiotics and without a proper diagnosis of the pathogen. Validated growth-based AST according to EUCAST or CLSI (European Committee on Antimicrobial Susceptibility Testing, Clinical Laboratory Standards Institute) recommendations is currently suggested to guide the antimicrobial therapy. Any new AST should be validated against these standard methods. Many rapid diagnostic techniques can already provide pathogen identification. Some of them can additionally detect the presence of resistance genes or resistance proteins, but usually isolated pure cultures are needed for AST. We discuss the value of the technologies applying nucleic acid amplification, whole genome sequencing, and hybridization as well as immunodiagnostic and mass spectrometry-based methods and biosensor-based AST. Additionally, we evaluate the potential of integrated systems applying microfluidics to integrate cultivation, lysis, purification, and signal reading steps. We discuss technologies and commercial products with potential for Point-of-Care Testing (POCT) and their capability to analyze polymicrobial samples without pre-purification steps. The purpose of this critical review is to present the needs and drivers for AST development, to show the benefits and limitations of AST methods, to introduce promising new POCT-compatible technologies, and to discuss AST technologies that are likely to thrive in the future.

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