Does Changing Step Width Alter Lower Extremity Biomechanics During Running?

A large percentage of runners incur a running related injury, with injury occurring most frequently at the knee. Runners with the most common overuse knee injuries have associated biomechanics that differ from healthy runners. Altering step width while running may influence those associated biomechanics. The purpose of this study was to determine the biomechanical response of lower extremity joints in healthy runners to increasing and decreasing step width during running. A preferred step width condition was collected first, followed in randomized order by a narrow step width condition and a wide step width condition. Step width was decreased to 0% of participant’s leg length during the narrow condition, and increased to 20% of participant’s leg length during the wide condition. Step width, peak lower extremity angles, peak lower extremity moments, and knee abduction impulse were recorded. Step width changed successfully in all conditions, and was similar between genders with no interaction effect. Peak hip adduction angle decreased as step width increased from narrowest to widest, and was larger in women compared to men without an interaction effect. Peak hip internal rotation angle remained similar among step width conditions and genders, with no interaction effect. Peak knee internal rotation angle increased when step width increased from narrowest to widest, and was larger in women than men with no interaction effect. Peak knee abduction moment decreased when step width increased from narrowest to widest, and was larger in men than women with no interaction effect. Knee abduction angular impulse decreased when step width increased from narrowest to widest, and was larger in men than women, with no interaction effect. Peak rearfoot eversion angle decreased when step width increased from narrowest to widest and was larger in women, with no interaction effect. Peak rearfoot inversion moment had a significant interaction effect, and decreased in male runners more than in female runners as step width increased from narrowest to widest. Findings suggest frontal plane biomechanics of healthy runners are influenced by step width

The national security key indicators as a part of economic development in the conditions of digitization

International audienceMethylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that C-13 nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing C-13 nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo

Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized C-13-methylglyoxal

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo

Metabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma.

13C MRI of hyperpolarized [1-13C]pyruvate metabolism has been used in oncology to detect disease, investigate disease progression, and monitor response to treatment with a view to guiding treatment in individual patients. This technique has translated to the clinic with initial studies in prostate cancer. Here, we use the technique to investigate its potential uses in patients with glioblastoma (GB). We assessed the metabolism of hyperpolarized [1-13C]pyruvate in an orthotopically implanted cell line model (U87) of GB and in patient-derived tumors, where these were produced by orthotopic implantation of cells derived from different patients. Lactate labeling was higher in the U87 tumor when compared with patient-derived tumors, which displayed intertumoral heterogeneity, reflecting the intra- and intertumoral heterogeneity in the patients' tumors from which they were derived. Labeling in some patient-derived tumors could be observed before their appearance in morphologic images, whereas in other tumors it was not significantly greater than the surrounding brain. Increased lactate labeling in tumors correlated with c-Myc-driven expression of hexokinase 2, lactate dehydrogenase A, and the monocarboxylate transporters and was accompanied by increased radioresistance. Because c-Myc expression correlates with glioma grade, this study demonstrates that imaging with hyperpolarized [1-13C]pyruvate could be used clinically with patients with GB to determine disease prognosis, to detect early responses to drugs that modulate c-Myc expression, and to select tumors, and regions of tumors for increased radiotherapy dose.Significance: Metabolic imaging with hyperpolarized [1-13C]pyruvate detects low levels of c-Myc-driven glycolysis in patient-derived glioblastoma models, which, when translated to the clinic, could be used to detect occult disease, determine disease prognosis, and target radiotherapy. Cancer Res; 78(18); 5408-18. ©2018 AACR.The work was supported by a Cancer Research UK Programme grant (17242) and by the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (16465) awarded to K. M. Brindle. F. Kreis was supported by a Marie Curie ITN studentship (EUROPOL) and R. Mair by Addenbrooke's Charitable Trust and a CRUK Cambridge Centre Fellowship

Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors.

The surveillance of antimicrobial-resistant isolates has proven to be one of the most valuable tools to understand the global rise of multidrug-resistant bacterial pathogens. We report the first insights into the current situation in the Caribbean, where a pilot project to monitor antimicrobial resistance (AMR) through phenotypic resistance measurements combined with whole-genome sequencing was set up in collaboration with the Caribbean Public Health Agency (CARPHA). Our first study focused on Klebsiella pneumoniae, a highly relevant organism amongst the Gram-negative opportunistic pathogens worldwide causing hospital- and community-acquired infections. Our results show that not only carbapenem resistance, but also hypervirulent strains, are circulating in patients in the Caribbean. Our current data does not allow us to infer their prevalence in the population. We argue for the urgent need to further support AMR surveillance and stewardship in this almost uncharted territory, which can make a significant impact on the reduction of antimicrobial usage. This article contains data hosted by Microreact (https://microreact.org)

A referenceless Nyquist ghost correction workflow for echo planar imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate.

Single-shot echo planar imaging (EPI), which allows an image to be acquired using a single excitation pulse, is used widely for imaging the metabolism of hyperpolarized 13 C-labelled metabolites in vivo as the technique is rapid and minimizes the depletion of the hyperpolarized signal. However, EPI suffers from Nyquist ghosting, which normally is corrected for by acquiring a reference scan. In a dynamic acquisition of a series of images, this results in the sacrifice of a time point if the reference scan involves a full readout train with no phase encoding. This time penalty is negligible if an integrated navigator echo is used, but at the cost of a lower signal-to-noise ratio (SNR) as a result of prolonged T2 * decay. We describe here a workflow for hyperpolarized 13 C EPI that requires no reference scan. This involves the selection of a ghost-containing background from a 13 C image of a single metabolite at a single time point, the identification of phase correction coefficients that minimize signal in the selected area, and the application of these coefficients to images acquired at all time points and from all metabolites. The workflow was compared in phantom experiments with phase correction using a 13 C reference scan, and yielded similar results in situations with a regular field of view (FOV), a restricted FOV and where there were multiple signal sources. When compared with alternative phase correction methods, the workflow showed an SNR benefit relative to integrated 13 C reference echoes (>15%) or better ghost removal relative to a 1 H reference scan. The residual ghosting in a slightly de-shimmed B0 field was 1.6% using the proposed workflow and 3.8% using a 1 H reference scan. The workflow was implemented with a series of dynamically acquired hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate images in vivo, resulting in images with no observable ghosting and which were quantitatively similar to images corrected using a 13 C reference scan

Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis.

Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented <5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake. SIGNIFICANCE: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death