A Complex Connection Between the Diversity of Human Gastric Mucin O-Glycans, Helicobacter pylori Binding, Helicobacter Infection and Fucosylation.

Helicobacter pylori colonizes the stomach of half of the human population. Most H. pylori are located in the mucus layer, which is mainly comprised by glycosylated mucins. Using mass spectrometry, we identified 631 glycans (whereof 145 were fully characterized and the remainder assigned as compositions) on mucins isolated from 14 Helicobacter spp.-infected and 14 Helicobacter spp.-noninfected stomachs. Only six identified glycans were common to all individuals, from a total of 60 to 189 glycans in each individual. An increased number of unique glycan structures together with an increased intraindividual diversity and larger interindividual variation were identified among O-glycans from Helicobacter spp.-infected stomachs compared with noninfected stomachs. H. pylori strain J99, which carries the blood group antigen-binding adhesin (BabA), the sialic acid-binding adhesin (SabA), and the LacdiNAc-binding adhesin, bound both to Lewis b (Leb)-positive and Leb-negative mucins. Among Leb-positive mucins, H. pylori J99 binding was higher to mucins from Helicobacter spp.-infected individuals than noninfected individuals. Statistical correlation analysis, binding experiments with J99 wt, and J99ΔbabAΔsabA and inhibition experiments using synthetic glycoconjugates demonstrated that the differences in H. pylori-binding ability among these four groups were governed by BabA-dependent binding to fucosylated structures. LacdiNAc levels were lower in mucins that bound to J99 lacking BabA and SabA than in mucins that did not, suggesting that LacdiNAc did not significantly contribute to the binding. We identified 24 O-glycans from Leb-negative mucins that correlated well with H. pylori binding whereof 23 contained α1,2-linked fucosylation. The large and diverse gastric glycan library identified, including structures that correlated with H. pylori binding, could be used to select glycodeterminants to experimentally investigate further for their importance in host-pathogen interactions and as candidates to develop glycan-based therapies.

Brachyspira Species Avidity to Colonic Mucins from Pigs with and without Brachyspira hyodysenteriae Infection Is Species Specific and Varies between Strains.

Brachyspira hyodysenteriae is commonly associated with swine dysentery (SD), a disease that has an economic impact on the swine industry. B. hyodysenteriae infection results in changes to the colonic mucus niche with massive mucus induction, which substantially increases the number of B. hyodysenteriae binding sites in the mucus. We previously determined that a B. hyodysenteriae strain binds to colon mucins in a manner that differs between pigs and mucin types. Here, we investigated if adhesion to mucins is a trait observed across a broad set of B. hyodysenteriae strains and isolates and furthermore at a genus level (B. innocens, B. pilosicoli, B. murdochii, B. hampsonii, and B. intermedia strains). Our results show that binding to mucins appears to be specific to B. hyodysenteriae, and within this species, the binding ability to mucins varies between strains/isolates, increases for mucins from pigs with SD, and is associated with sialic acid epitopes on mucins. Infection with B. hyodysenteriae strain 8dII results in mucin glycosylation changes in the colon, including a shift in sialic acid-containing structures. Thus, we demonstrate through hierarchical cluster analysis and orthogonal projections to latent structures discriminant analysis (OPLS-DA) models of the relative abundances of sialic acid-containing glycans that sialic acid-containing structures in the mucin O-glycome are good predictors of B. hyodysenteriae strain 8dII infection in pigs. The results emphasize the role of sialic acids in governing B. hyodysenteriae interactions with its host, which may open perspectives for therapeutic strategies.

Commercial head-mounted display virtual reality for upper extremity rehabilitation in chronic stroke: a single-case design study.

BACKGROUND: Rehabilitation is crucial for maximizing recovery after stroke. Rehabilitation activities that are fun and rewarding by themselves can be more effective than those who are not. Gamification with virtual reality (VR) exploits this principle. This single-case design study probes the potential for using commercial off-the-shelf, room-scale head-mounted virtual reality for upper extremity rehabilitation in individuals with chronic stroke, the insights of which can inform further research. METHODS: A heterogeneous volunteer sample of seven participants living with stroke were recruited through advertisement. A single-case design was employed with a 5-week baseline (A), followed by a 10-week intervention (B) and a 6-month follow-up. Upper extremity motor function was assessed with validated kinematic analysis of drinking task. Activity capacity was assessed with Action Research Arm Test, Box and Block Test and ABILHAND questionnaire. Assessments were done weekly and at follow-up. Playing games on a VR-system with head-mounted display (HTC Vive) was used as rehabilitation intervention. Approximately 300 games were screened and 6 tested. Visual analysis and Tau-U statistics were used to interpret the results. RESULTS: Visual analysis of trend, level shift and overlap as well as Tau-U statistics indicated improvement of Action Research Arm Test in six participants. Four of these had at least a moderate Tau-U score (0.50-0.92), in at least half of the assessed outcomes. These four participants trained a total of 361 to 935 min. Two out of four participants who were able to perform the drinking task, had the highest training dose (> 900 min) and showed also improvements in kinematics. The predominant game played was Beat Saber. No serious adverse effects related to the study were observed, one participant interrupted the intervention phase due to a fall at home. CONCLUSIONS: This first study of combining commercial games, a commercial head-mounted VR, and commercial haptic hand controls, showed promising results for upper extremity rehabilitation in individuals with chronic stroke. By being affordable yet having high production values, as well as being an easily accessible off-the-shelf product, this variant of VR technology might facilitate widespread adaption. Insights garnered in this study can facilitate the execution of future studies. Trial registration The study was registered at researchweb.org (project number 262331, registered 2019-01-30, https://www.researchweb.org/is/vgr/project/262331 ) prior to participant enrolment.

Virtual reality gaming in rehabilitation after stroke - user experiences and perceptions.

PURPOSE: The present study explored participants' experiences with and perceptions of using fully immersive head-mounted virtual reality (VR) gaming as rehabilitation after stroke. METHODS: Four men and three women (median age 64 years) with chronic stroke and varying motor impairment (mild to severe) were interviewed after 10 weeks of VR training on the commercial HTC Vive system, focusing on the upper extremities. Inductive qualitative thematic analysis was performed. RESULTS: The analysis revealed three main themes: playing the game, benefits and effects, and personalizing the game. Playing the game encompasses both the feeling of being immersed in the game and descriptions of the gaming being motivating and fun. Benefits and effects describe the participants' expectations of potential benefits, the importance of getting feed-back, and the impact in daily life. Personalizing the game includes finding the right game and level, and the participants' need for support to achieve full use of the training. CONCLUSIONS: Participants with chronic stroke described the fully immersive VR gaming intervention as a fun and motivating way to improve their functioning in everyday life. Qualitative studies are needed to explore how people with stroke perceive VR gaming when it is implemented in real clinical environments.Clinical implicationsVR gaming was perceived as a positive and motivating rehabilitation after stroke.Getting feedback and perceiving benefits are essential parts of VR rehabilitation.Commercial fully immersive VR-games might be an option for stroke rehabilitation when the game can be personalized and support is available.

Helicobacter suis infection alters glycosylation and decreases the pathogen growth inhibiting effect and binding avidity of gastric mucins.

Helicobacter suis is the most prevalent non-Helicobacter pylori Helicobacter species in the human stomach and is associated with chronic gastritis, peptic ulcer disease, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. H. suis colonizes the gastric mucosa of 60-95% of pigs at slaughter age, and is associated with chronic gastritis, decreased weight gain, and ulcers. Here, we show that experimental H. suis infection changes the mucin composition and glycosylation, decreasing the amount of H. suis-binding glycan structures in the pig gastric mucus niche. Similarly, the H. suis-binding ability of mucins from H. pylori-infected humans is lower than that of noninfected individuals. Furthermore, the H. suis growth-inhibiting effect of mucins from both noninfected humans and pigs is replaced by a growth-enhancing effect by mucins from infected individuals/pigs. Thus, Helicobacter spp. infections impair the mucus barrier by decreasing the H. suis-binding ability of the mucins and by decreasing the antiprolific activity that mucins can have on H. suis. Inhibition of these mucus-based defenses creates a more stable and inhabitable niche for H. suis. This is likely of importance for long-term colonization and outcome of infection, and reversing these impairments may have therapeutic benefits.