Prospective clinical evaluation of a novel anatomic cuff for forearm crutches in patients with osteoarthritis.

The use of forearm crutches has been associated with pain and neuropraxia along the ulnar bone. Whilst anatomic grips have improved comfort of crutch walking, to date anatomic forearm cuffs have not been clinically evaluated. The aim of this clinical pilot study was to determine if the use of forearm crutches with anatomic cuffs reduces pain and increases comfort and function in long-term users of forearm crutches during a 4-week period. Prospective study in ten patients suffering from end-stage osteoarthritis of the lower extremity. All participants were long-term users of conventional forearm crutches. Participants used forearm crutches with an anatomically shaped cuff for 4-weeks. General health was assessed using the SF-36, and the crutches were evaluated using a newly developed questionnaire focusing on symptoms along the forearm. Pain and paresthesia along the forearms decreased by 3.3 points (95% confidence interval difference (CI): [-5.0; -1.6], p = .004) and 3.5 points (95%CI: [-5.1; -1.9], p = .002), respectively, after using the crutches with the new anatomic cuff for 4 weeks. Comfort and sense of security of crutch use increased by 3.0 points (95%CI: [1.3; 4.7], p = .007) and 2.4 points (95%CI: [0.7; 4.1], p = .024). Cross-correlation analysis revealed correlations among items in the same item category and no correlations between items of different item categories of the new questionnaires. An anatomically shaped cuff increases comfort of forearm crutches. Further research should confirm long-term clinical improvement. This study was registered retrospectively in ISRCTN (TRN: ISRCTN 11135150 ) on 14/02/2017

Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.

Serum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8+ T cells to produce IFN-γ. Whether acetate modulates memory CD8+ T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8+ T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly activating glutaminase, thereby augmenting glutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggered calcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducing immunopathology. This indicates that, during different stages of the immune response, the same metabolite-acetate-induces distinct immunometabolic programs within the same cell type

Assembly of 913 microbial genomes from metagenomic sequencing of the cow rumen

The Rowett Institute and SRUC are core funded by the Rural and Environment Science and Analytical Services Division (RESAS) of the Scottish Government. The Roslin Institute forms part of the Royal (Dick) School of Veterinary Studies, University of Edinburgh. This project was supported by the Biotechnology and Biological Sciences Research Council (BBSRC; BB/N016742/1, BB/N01720X/1), including institute strategic programme and national capability awards to The Roslin Institute (BBSRC: BB/P013759/1, BB/P013732/1, BB/J004235/1, BB/J004243/1); and by the Scottish Government as part of the 2016–2021 commission.Peer reviewedPublisher PD

Systematic investigation and comparison of FDA-approved immunosuppressive drugs FK506, cyclosporine and rapamycin for neuromuscular regeneration following chronic nerve compression injury

Aim: To compare therapeutic benefits of different immunophilin ligands for treating nerve injuries.Materials & methods: Cyclosporine, FK506 and rapamycin, were evaluated firstin vitroon a serum-free culture of embryonic dorsal root ganglia followed by a newin vivomodel of chronic nerve compression.Results: Outcomes of thein vitrostudy have shown a potent effect of cyclosporine and FK506, on dorsal root ganglia axonal outgrowth, comparable to the effect of nerve growth factor. Rapamycin exhibited only a moderate effect. Thein vivostudy revealed the beneficial effects of Cyclosporine, FK506 and rapamycin for neuromuscular regeneration. Cyclosporine showed the better maintenance of the tissues and function.Conclusion: Cyclosporine, FK506 and rapamycin drugs showed potential for treating peripheral nerve chronic compression injuries

The effects of a ration change from a total mixed ration to pasture on rumen fermentation, volatile fatty acid absorption characteristics, and morphology of dairy cows

To investigate the effect of the change from a concentrate and silage-based ration (total mixed ration, TMR) to a pasture-based ration, a 10-wk trial (wk 1-10) was performed, including 10 rumen- and duodenum-fistulated German Holstein dairy cows (182 ± 24 d in milk, 23.5 ± 3.5 kg of milk/d; mean ± standard deviation). The cows were divided in either a pasture group (PG, n = 5) or a confinement group (CG, n = 5). The CG stayed on a TMR-based ration (35% corn silage, 35% grass silage, 30% concentrate; dry matter basis), whereas the PG was gradually transitioned from a TMR to a pasture-based ration (wk 1: TMR only; wk 2: 3 h/d on pasture wk 3 and 4: 12 h/d on pasture wk 5-10: pasture only). Ruminal pH, volatile fatty acids (VFA), NH3-N, and lipopolysaccharide (LPS) concentrations were measured in rumen fluid samples collected medially and ventrally on a weekly basis. Ruminal pH was continuously recorded during 1 to 4 consecutive days each week using ruminal pH measuring devices. In wk 1, 5, and 10, rumen contents were evacuated and weighed, papillae were collected from 3 locations in the rumen, and subsequently a VFA absorption test was performed. In the PG, mean rumen pH and molar acetate proportions decreased, and molar butyrate proportions increased continuously over the course of the trial, which can most likely be ascribed to an increased intake of rapidly fermentable carbohydrates. During the first weeks on a full grazing ration (wk 5-7), variation of rumen pH decreased, and in wk 5 a lower rumen content, papillae surface area, and potential for VFA absorption were observed. In wk 8 to 10, variation of rumen pH and total VFA concentrations increased again, and acetate/propionate ratio decreased. In wk-10 rumen content, papillae area and VFA absorption characteristics similar to initial levels were observed. Although continuous rumen pH assessments and LPS concentrations did not reveal an increased risk for subacute rumen acidosis (SARA) during the adaption period, histopathology of rumen papillae and potential for VFA absorption indicated a possible risk for rumen health. An increased risk for SARA was observed in wk 9 and 10 in the PG, but rumen LPS concentrations and histopathology were not adversely affected. Results of the present study suggest that after behavioral and metabolic adaptation to the transition from a TMR to a pasture-based ration, no adverse effects on rumen morphology and absorption capacity occurred, although rumen pH after adaptation to pasture indicated increased risk of SARA.</p

Author Correction: Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity.

ISSN:2041-172

Innate immunity restricts <i>Citrobacter rodentium</i> A/E pathogenesis initiation to an early window of opportunity

<div><p><i>Citrobacter rodentium</i> infection is a mouse model for the important human diarrheal infection caused by enteropathogenic <i>E</i>. <i>coli</i> (EPEC). The pathogenesis of both species is very similar and depends on their unique ability to form intimately epithelium-adherent microcolonies, also known as “attachment/effacement” (A/E) lesions. These microcolonies must be dynamic and able to self-renew by continuous re-infection of the rapidly regenerating epithelium. It is unknown whether sustained epithelial A/E lesion pathogenesis is achieved through re-infection by planktonic bacteria from the luminal compartment or local spread of sessile bacteria without a planktonic phase. Focusing on the earliest events as <i>C</i>. <i>rodentium</i> becomes established, we show here that all colonic epithelial A/E microcolonies are clonal bacterial populations, and thus depend on local clonal growth to persist. In wild-type mice, microcolonies are established exclusively within the first 18 hours of infection. These early events shape the ongoing intestinal geography and severity of infection despite the continuous presence of phenotypically virulent luminal bacteria. Mechanistically, induced resistance to A/E lesion de-novo formation is mediated by TLR-MyD88/Trif-dependent signaling and is induced specifically by virulent <i>C</i>. <i>rodentium</i> in a virulence gene-dependent manner. Our data demonstrate that the establishment phase of <i>C</i>. <i>rodentium</i> pathogenesis <i>in vivo</i> is restricted to a very short window of opportunity that determines both disease geography and severity.</p></div