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Background: Folate (vitamin B9) occurs naturally mainly as tetrahydrofolate (THF), methyl-tetrahydrofolate (M-THF), and formyl-tetrahydrofolate (F-THF), and as dietary synthetic form (folic acid). While folate auxotrophy and prototrophy are known for several gut microbes, the specific folate forms produced by gut prototrophs and their impact on gut auxotrophs and microbiota remain unexplored., Methods: Here, we quantified by UHPLC-FL/UV folate produced by six predicted gut prototrophs (Marvinbryantia formatexigens DSM 14469, Blautia hydrogenotrophica 10507  T , Blautia producta DSM 14466, Bacteroides caccae DSM 19024, Bacteroides ovatus DSM 1896, and Bacteroides thetaiotaomicron DSM 2079  T ) and investigated the impact of different folate forms and doses (50 and 200 µg/l) on the growth and metabolism of the gut auxotroph Roseburia intestinalis in pure cultures and during fecal anaerobic batch fermentations (48 h, 37 °C) of five healthy adults., Results: Our results confirmed the production of folate by all six gut strains, in the range from 15.3 ng/ml to 205.4 ng/ml. Different folate forms were detected, with THF ranging from 12.8 to 41.4 ng/ml and 5-MTHF ranging from 0.2 to 113.3 ng/ml, and being detected in all strains. Natural folate forms, in contrast to folic acid, promoted the growth and metabolism of the auxotroph R. intestinalis L1-82, with dose-dependent effects. During fecal batch fermentations, folate forms at both levels had no detectable effect on total bacteria concentration, on gut community composition and metabolic activity and on Roseburia spp. abundance, compared to the control without folate addition., Conclusions: Our study demonstrates for the first time in vitro the production of different natural folate forms by predicted gut prototrophs and the stimulation on the growth of the folate auxotrophic butyrate-producing R. intestinalis L1-82. Surprisingly, folate did not impact fecal fermentations. Our data suggest that the dietary folate forms at the tested levels may only have limited effects, if any, on the human gut microbiota in vivo., (© 2024. The Author(s).)

Background: Gut microbial features and the role of early life stress in pediatric functional abdominal pain-not otherwise specified (FAP-NOS) have never been investigated before. Here, we hypothesize that early life stress is more prevalent in FAP-NOS compared to healthy controls and that fecal microbial profiles and related metabolites differ between groups. Methods: In an international multicenter case-control study, FAP-NOS patients ( n = 40) were compared to healthy controls ( n = 55). Stool samples and demographic and clinical data including early life traumatic events and antibiotics treatments were collected from children aged four to twelve years. Fecal microbial profiles were assessed with 16S rRNA gene amplicon sequencing. Microbial metabolite concentrations in fecal supernatant, including short-chain fatty acids and amino acids, were detected via liquid chromatography. Results: Microbial richness was increased in FAP-NOS compared to healthy controls and microbial composition (unweighted UniFrac) differed between groups. Three distinct amplicon sequencing variants and two distinct species were enriched in FAP-NOS compared to controls, with no observed changes at higher taxonomic levels. No differences in microbial metabolites and early life stress were observed between groups. Conclusion: The presented hypothesis could not be proven, with no observed differences in occurrence of early life stress, and fecal microbial metabolic profiles between pediatric FAP-NOS and healthy controls. Pediatric FAP-NOS patients exhibited mild differences in the fecal microbial community compared with controls. Further large-scale studies with high-resolution techniques are warranted to address the biological relevance of present observations., Competing Interests: Christophe Lacroix is an Editorial Board member of the journal Microbiome Research Reports, while the other authors have declared that they have no conflicts of interest., (© The Author(s) 2024.)

The anaerobic cultivation of fecal microbiota is a promising approach to investigating how gut microbial communities respond to specific intestinal conditions and perturbations. Here, we describe a flexible protocol using 96-deepwell plates to cultivate stool-derived gut microbiota. Our protocol aims to address gaps in high-throughput culturing in an anaerobic chamber. We characterized the influence of the gas phase on the medium chemistry and microbial physiology and introduced a modular medium preparation process to enable the testing of several conditions simultaneously. Furthermore, we identified a medium formulation that maximized the compositional similarity of ex vivo cultures and donor microbiota while limiting the bloom of Enterobacteriaceae . Lastly, we validated the protocol by demonstrating that cultivated fecal microbiota responded similarly to dietary fibers (resistant dextrin, soluble starch) and drugs (ciprofloxacin, 5-fluorouracil) as reported in vivo. This high-throughput cultivation protocol has the potential to facilitate culture-dependent studies, accelerate the discovery of gut microbiota-diet-drug-host interactions, and pave the way to personalized microbiota-centered interventions., Competing Interests: C.M., P.B., T.W., and G.L. are or were employees of PharmaBiome AG. T.W. and C.L. are founders of PharmaBiome AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

To produce the health-associated metabolite propionate, gut microbes require vitamin B12 as a cofactor to convert succinate to propionate. B12 is sourced in the human gut from the unabsorbed dietary fraction and in situ microbial production. However, experimental data for B12 production by gut microbes is scarce, especially on their produced B12-analogues. Further, the promotion of propionate production by microbially-produced and dietary B12 is not yet fully understood. Here, we demonstrated B12 production in 6 out of 8 in silico predicted B12-producing bacteria from the human gut. Next, we showed in vitro that B12 produced by Blautia hydrogenotrophica , Marvinbryantia formatexigens, and Blautia producta promoted succinate to propionate conversion of two prevalent B12-auxotrophic gut bacteria, Akkermansia muciniphila and Bacteroides thetaiotaomicron . Finally, we examined the propiogenic effect of commercially available B12-analogues present in the human diet (cyano-B12, adenosyl-B12 and hydroxy-B12) at two doses. The low dose resulted in partial conversion of succinate to propionate for A. muciniphila when grown with adenosyl-B12 (14.6 ± 2.4 mM succinate and 18.7 ± 0.6 mM propionate) and hydroxy-B12 (13.0 ± 1.1 mM and 21.9 ± 1.2 mM), in comparison to cyano-B12 (0.7 ± 0.1 mM and 34.1 ± 0.1 mM). Higher doses of adenosyl-B12 and hydroxy-B12 resulted in significantly more conversion of succinate to propionate in both propionate-producing species, compared to the low dose. B12 analogues have different potential to impact the propionate metabolism of prevalent propionate producers in the gut. These results could contribute to strategies for managing gut disorders associated with decreased propionate production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kundra, Greppi, Duppenthaler, Plüss, Pugin, Lacroix and Geirnaert.)

Background: Manual wheelchair propulsion is widely accepted to be biomechanically inefficient, with a high prevalence of shoulder pain and injuries among users. Directional control during wheelchair movement is a major, yet largely overlooked source of energy loss: changing direction or maintaining straightforward motion on tilted surfaces requires unilateral braking. This study evaluates the efficiency of a novel steering-by-leaning mechanism that guides wheelchair turning through upper body leaning., Methods: 16 full-time wheelchair users and 15 able-bodied novices each completed 12 circuits of an adapted Illinois Agility Test-course that included tilted, straight, slalom, and 180° turning sections in a prototype wheelchair at a self-selected functional speed. Trials were alternated between conventional and steering-by-leaning modes while propulsion forces were recorded via instrumented wheelchair wheels. Time to completion, travelled distance, positive/negative power, and work done, were all calculated to allow comparison of the control modes using repeated measures analysis of variance., Results: Substantial average energy reductions of 51% (able-bodied group) and 35% (wheelchair user group) to complete the task were observed when using the steering-by-leaning system. Simultaneously, able-bodied subjects were approximately 23% faster whereby completion times did not differ for wheelchair users. Participants in both groups wheeled some 10% further with the novel system. Differences were most pronounced during turning and on tilted surfaces where the steering-by-leaning system removed the need for braking for directional control., Conclusions: Backrest-actuated steering systems on manual wheelchairs can make a meaningful contribution towards reducing shoulder usage while contributing to independent living. Optimisation of propulsion techniques could further improve functional outcomes., (© 2023. The Author(s).)

Introduction: Force measurement wheels are essential instruments for analysing manual wheelchair propulsion. Existing solutions are heavy and bulky, influence propulsion biomechanics, and are limited to confined laboratory environments. In this paper, a novel design for a compact and lightweight measurement wheel is presented and statically validated., Methods: Four connectors between the push-rim and wheel-rim doubled as force sensors to allow the calculation of tangential and radial forces as well as the point of force application. For validation, increasing weights were hung on the push-rim at known positions. Resulting values were compared against pre-determined force components., Results: The implemented prototype weighed 2.1 kg and was able to transmit signals to a mobile recording device at 140 Hz. Errors in forces at locations of propulsive pushes were in the range up to ±3.1 N but higher at the frontal extreme. Tangential force components were most accurate., Conclusion: The principle of instrumenting the joints between push-rim and wheel-rim shows promise for assessing wheelchair propulsion in daily life., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Uricase catalyzes the conversion of uric acid into allantoin with concomitant reduction of molecular oxygen to hydrogen peroxide. In humans, uricase is not functional, thereby predisposing individuals to hyperuricemia, a metabolic disturbance associated with gout, chronic kidney disorders, and cardiovascular diseases. The efficacy of current therapies to treat hyperuricemia is limited, and novel approaches are therefore desired, for instance using uricase-expressing probiotic strains. Here, we evaluated UV-spectrophotometric and H 2 O 2 -based fluorescent assays to enable the rapid identification of uricase activity in a broad panel of lactobacilli, Bacillus , and Bifidobacterium species. We highlighted abiotic (medium composition and mode of sterilization) and biotic (H 2 O 2 -producing strains) factors impacting the measurements' accuracy, and reported on the stepwise optimization of a simple, fast, and robust high-throughput UV-spectrophotometric method to screen uricase activity using whole bacterial suspension, thereby assessing both cell-associated and extracellular activity. The validity of the optimized assay, based on the monitoring of uric acid degradation at 300 nm, was confirmed via liquid chromatography. Finally, a panel of 319 Qualified Presumption of Safety (QPS) strains of lactobacilli (18 species covering nine genera), Bacillus (three species), and Bifidobacterium (four species) were screened for uricase activity using the optimized method. All 319 strains, but the positive control Bacillus sp. DSM 1306, were uricase-negative, indicating that this activity is rare among these genera, especially in isolates from food or feces. Altogether, the UV-spectrophotometric high-throughput assay based on whole bacterial suspension reported here can be used to rapidly screen large microbial collections, by simultaneously detecting cell-associated and extracellular uricase activity, thereby accelerating the identification of uricolytic strains with therapeutic potential to treat hyperuricemia., Competing Interests: RN works for the company Beo Therapeutics AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pugin, Plüss, Mujezinovic, Nielsen and Lacroix.)

Pressure ulcers (PUs) result from localised injury to the skin and underlying tissue and usually occur over a bony prominence as a result of pressure, often in combination with shear forces. Both pressure magnitude and duration are thought to be key risk factors in the occurrence of PUs, thus exposing wheelchair-bound subjects to high risk of PU development. As a result, wheelchairs that incorporate tilt-in-space and recline functions are routinely prescribed to redistribute pressure away from their ischial tuberosities. The goal of this study was to analyse the role of full-body tilt and recline angles in governing sitting interface pressure and blood circulation parameters in elderly subjects and thereby investigate the efficacy of tilt-in-space wheelchairs for aiding pressure relief activity. Sitting interface pressure and ischial blood flow parameters were examined in 20 healthy elderly subjects while seated in a tilt-in-space and recline wheelchair. Five different angles of seat tilt (5°, 15°, 25°, 35°, and 45°) were assessed in combination with three different angles of backrest recline (5°, 15°, and 30°). The results of the study show that when compared to the upright reference posture, every position (except 15°T/5°R) resulted in a significant decrease in sitting interface pressure. Ischial blood flow also showed significant increases at four different positions (45°T/15°R, 15°T/30°R, 35°T/30°R, and 45°T/30°R) but only at larger tilt-in-space and recline angles. The results therefore suggest that small tilt-in-space and recline angles are indeed able to reduce sitting interface pressures, whereas changes in ischial blood flow only occur at larger angles. In the literature, cell deformation is thought to be dominant over tissue ischemia in the development of tissue necrosis and PUs. Therefore, together with our findings it can be concluded that frequently undertaking small adjustments in tilt-in-space and recline angle might be important for preventing cell deformation and any associated cell necrosis. Larger angles of tilt-in-space and recline seem to support blood flow returning to the tissues, which is likely to play a positive role in healing damaged tissue.

As hill jumps are very time-consuming, ski jumping athletes often perform various imitation jumps during training. The performed jumps should be similar to hill jumps, but a direct comparison of the kinetic and kinematic parameters has not been performed yet. Therefore, this study aimed to correlate 11 common parameters during hill jumps (Oberstdorf Germany), squat jumps (wearing indoor shoes), and various imitation jumps (rolling 4°, rolling flat, static; jumping equipment or indoor shoes) on a custom-built instrumented vehicle with a catch by the coach. During the performed jumps, force and video data of the take-off of 10 athletes were measured. The imitation and squat jumps were then ranked. The main difference between the hill jumps and the imitation and squat jumps is the higher maximal force loading rate during the hill jumps. Imitation jumps performed on a rolling platform, on flat ground were the most similar to hill jumps in terms of the force-time, and leg joint kinematic properties. Thus, non-hill jumps with a technical focus should be performed from a rolling platform with a flat inrun with normal indoor shoes or jumping equipment, and high normal force loading rates should be the main focus of imitation training.

Occupational musculoskeletal disorders, particularly chronic low back pain (LBP), are ubiquitous due to prolonged static sitting or nonergonomic sitting positions. Therefore, the aim of this study was to develop an instrumented chair with force and acceleration sensors to determine the accuracy of automatically identifying the user's sitting position by applying five different machine learning methods (Support Vector Machines, Multinomial Regression, Boosting, Neural Networks, and Random Forest). Forty-one subjects were requested to sit four times in seven different prescribed sitting positions (total 1148 samples). Sixteen force sensor values and the backrest angle were used as the explanatory variables (features) for the classification. The different classification methods were compared by means of a Leave-One-Out cross-validation approach. The best performance was achieved using the Random Forest classification algorithm, producing a mean classification accuracy of 90.9% for subjects with which the algorithm was not familiar. The classification accuracy varied between 81% and 98% for the seven different sitting positions. The present study showed the possibility of accurately classifying different sitting positions by means of the introduced instrumented office chair combined with machine learning analyses. The use of such novel approaches for the accurate assessment of chair usage could offer insights into the relationships between sitting position, sitting behaviour, and the occurrence of musculoskeletal disorders.

Aircraft noise contours are estimated using model calculations and, due to their impact on land use planning, they need to be highly accurate. During night time, not only the number and dominant types of aircraft may differ from daytime but also the flight paths flown may differ. To determine to which detail these variations in flight paths need to be considered, calculations were performed exemplarily for two airports using all available radar data over 1 year, taking into account their changes over the day. The results of this approach were compared with results of a simpler approach which does not consider such changes. While both calculations yielded similar results for the day and close to the airport, differences increased with distance as well as with the period of day (day

Background: Aim was to analyze the association between local infection and amputation rate in patients with chronic critical limb ischemia (CLI) with or without successful revascularization., Patients and Methods: We performed a retrospective analysis of 56 consecutive patients with 57 critically ischemic legs seen at the University Hospital Bern. Patients with CLI were selected if ischemic lesions and follow-up of more than 2 months were documented. Infection was suggested when 2 of the following criterion were present: temperature > 37 degrees C, C-reactive protein > 50 mg/L, leukocytes > 10 x 10(3)/microliter ("2 of 3" criterion), or a putrid secretion was documented ("secretion" criterion)., Results: In patients with successful revascularization (n = 39), there was a significant shift from 10.3% major to 33.3% minor amputations (Chi Square p value = 0.014) as compared to patients without or with failed revascularization (n = 18) with 44.4% and 11.1% (Chi Square p value = 0.008), respectively. An infection was suggested in 22 of 53 limbs (41.5%) according to the "2 of 3" criterion, and 30 of 57 limbs (52.6%) satisfying the "secretion" criterion. Both criteria, were significantly more common in patients undergoing amputation as compared to patients without amputation (p = 0.001). Multiple lesions were more common in patients with major amputations (p = 0.026)., Conclusion: Successful revascularization effectively reduces major amputations and leads to healing of ischemic ulcers. Secondary foot infections are frequent. Infections are associated with a significantly higher rate of minor and major amputations, also in patients with successful revascularization, and should be treated adequately as well as in time with antibiotics.