Francisella tularensisis a facultative intracellular bacterial pathogen capable of proliferating within host macrophages. The mechanisms that explain the differences in virulence between various strains of the species are not well characterized. In the present study, we show that both attenuated (strain LVS) and virulent (strains FSC200 and SCHU S4) strains of the pathogen replicate at similar rates in resting murine peritoneal exudate cells (PEC). However, when PEC were activated by exposure to gamma interferon (IFN-γ), they killed LVS more rapidly than virulent strains of the pathogen. Addition ofN^G-monomethyl-l-arginine, an inhibitor of inducible nitric oxide synthase, to IFN-γ-treated PEC, completely inhibited killing of the virulent strains, whereas it only partially blocked the killing of LVS. Similarly, in a cell-free system, SCHU S4 and FSC200 were more resistant to killing by H₂O₂and ONOO⁻thanF. tularensisLVS. Catalase encoded bykatGis a bacterial factor that can detoxify bactericidal compounds such as H₂O₂and ONOO⁻. To investigate its contribution to the virulence ofF. tularensis,katGdeletion-containing mutants of SCHU S4 and LVS were generated. Both mutants demonstrated enhanced susceptibility to H₂O₂in vitro but replicated as effectively as the parental strains in unstimulated PEC. In mice, LVS-ΔkatGwas significantly attenuated compared to LVS whereas SCHU S4-ΔkatG, despite slower replication, killed mice as quickly as SCHU S4. This implies that clinical strains of the pathogen havekatG-independent mechanisms to combat the antimicrobial effects exerted by H₂O₂and ONOO⁻, the loss of which could have contributed to the attenuation of LVS.

Social participation and digital engagement can contribute to health and well-being among older adults. Because of older adults’ decline in abilities, coupled with complex technology and its perceived insufficient relevance to daily life, there is a need to create and tailor social opportunities and services that are supported by digital technologies for older adults to continue participating in society. Thus, it becomes relevant to explore older adults’ perceptions about contexts surrounding their social participation in a digital society. This exploration used a qualitative research design with focus group interviews and qualitative content analysis. Eighteen older adults, aged 66–81 years, from rural communities in Northern Sweden, participated in this study. The analysis resulted in three categories: experiencing conditions for social participation in a state of flux, perceiving drawbacks of urbanization on social participation, and welcoming digital technology that facilitates daily and community living. These categories were encapsulated in the theme—the juxtaposition of narrowing offline social networks and expanding digital opportunities for social participation. The findings suggested that co-creating usable digitalized services and facilitating satisfactory use of digital technologies could support older adults’ social participation through activities that they find relevant in their lives, and subsequently, might enable them to live longer at home.

Exercise is effective in order to prevent falls in community-dwelling older people. Self-management programs have the potential to increase access and reduce costs related to exercise-based fall prevention. However, information regarding older people’s views of participating in such programs is needed to support implementation. The aim of this study was to explore older people’s experiences of a self-management fall prevention exercise routine guided either by a digital program (web-based or mobile) or a paper booklet. This qualitative study was part of a feasibility study exploring two completely self-managed exercise interventions in which the participants tailored their own program, guided either by a digital program or a paper booklet. Individual face-to-face semi-structured interviews were conducted with a purposeful sample of 28 participants (18 women), mean age 76 yrs. Qualitative content analysis was used to analyse the data. Self-managing and self-tailoring these exercise programs was experienced as ‘Managing pieces of a personal puzzle’. To independently being able to create a program and manage exercise was described in the categories ‘Finding my own level’ and ‘Programming it into my life’. The participants experienced the flexibility and independence provided by completely self-managed exercise as positive and constructive although it required discipline. Furthermore, different needs and preferences when managing their exercise were described, as well as varying sources of motivation for doing the exercise, as highlighted in the category ‘Defining my source of motivation’. The category ‘Evolving my acquired knowledge’ captures the participants’ views of building their competence and strategies for maintenance of the exercise. It describes a combined process of learning the program and developing reflection, which was more clearly articulated by participants using the digital program. This study provides new knowledge regarding experiences, preferences and motivations of older people to engage in home-based self-managed fall prevention exercise. They expressed both a capability and willingness to independently manage their exercise. A digital program seems to have strengthened the feeling of support while creating their own exercise program and tailoring it to their preferences and circumstances, which might therefore create better opportunities for adoption and adherence in the long term.

Using a strategy of gene deletion mutagenesis, we have examined the roles of genes putatively involved in lipopolysaccharide biosynthesis in the virulent facultative intracellular bacterial pathogen, Francisella tularensis subspecies tularensis, strain SCHU S4 in LPS biosynthesis, protein glycosylation, virulence and immunogenicity. One mutant, ∆wbtI, did not elaborate a long chain O-polysaccharide (OPS), was completely avirulent for mice, and failed to induce a protective immune response against challenge with wild type bacteria. Another mutant, ∆wbtC, produced a long chain OPS with altered chemical and electrophoretic characteristics. This mutant showed markedly reduced glycosylation of several known glycoproteins. Additionally this mutant was highly attenuated, and elicited a protective immune response against systemic, but not respiratory challenge with wild type SCHU S4. A third mutant, ∆kdtA, produced an unconjugated long chain OPS, lacking a detectable core structure, and which was not obviously expressed at the surface. It was avirulent and elicited partial protection against systemic challenge only.

Background: The Francisella tularensis protein MglA performs complex regulatory functions since it influences the expression of more than 100 genes and proteins in F. tularensis. Besides regulating the igl operon, it has been suggested that it also regulates several factors such as SspA, Hfq, CspC, and UspA, all important to stress adaptation. Therefore, it can be hypothesized that MglA plays an important role for Francisella stress responses in general and for the oxidative stress response specifically. Results: We investigated the oxidative stress response of the ΔmglA mutant of the live vaccine strain (LVS) of F. tularensis and found that it showed markedly diminished growth and contained more oxidized proteins than the parental LVS strain when grown in an aerobic milieu but not when grown microaerobically. Moreover, the ΔmglA mutant exhibited an increased catalase activity and reduced expression of the fsl operon and feoB in the aerobic milieu. The mutant was also found to be less susceptible to H₂O₂. The aberrant catalase activity and gene expression was partially normalized when the ΔmglA mutant was grown in a microaerobic milieu. Conclusions: Altogether the results show that the ΔmglA mutant exhibits all the hallmarks of a bacterium subjected to oxidative stress under aerobic conditions, indicating that MglA is required for normal adaptation of F. tularensis to oxidative stress and oxygen-rich environments.