Association between musculoskeletal ultrasonography and bone remodelling markers and its role in disease monitoring of gout and hyperuricaemia.

OBJECTIVES: To evaluate associations between bone destruction markers and musculoskeletal ultrasonography (MU) findings in patients with gout and hyperuricaemia and clarify the role of MU in treatment responsiveness. METHODS: One-hundred and fifty patients with gout and 100 patients with hyperuricaemia were divided into five groups according to MU manifestations. Circulating Dickkopf-1 (DKK-1) and receptor activator of nuclear factor-κB ligand (RANKL) levels were measured. Thirty patients from the gout group and 10 from the hyperuricaemia group, were treated for 1 year with urate-lowering therapy (ULT). RESULTS: Patients with gout and tophus and/or bone erosion had the highest DKK-1 and RANKL levels. Patients with gout and MU-evidenced aggregates and/or double-contour signs had higher DKK-1 and RANKL levels than the normal MU group (p<0.001). Patients with hyperuricaemia and abnormal MU findings had significantly higher DKK-1 and RANKL levels than those with normal MU findings. DKK-1 and RANKL levels positively correlated with disease duration in patients with gout (r=0.430, p<0.001; r=0.359, p<0.001, respectively) and hyperuricaemia (r=0.446, p<0.001; r=0.379, p<0.001, respectively). After ULT, MU abnormalities disappeared in 12 and 8 patients with gout and hyperuricaemia, respectively. The largest tophus diameter decreased in patients with gout (t=6.092, p<0.001). DKK-1 and RANKL concentrations significantly decreased in all patients. Lower serum urate levels corresponded with higher ratios of normal MU features in all patients. CONCLUSIONS: In patients with gout and hyperuricaemia, MU manifestations were associated with DKK-1 and RANKL levels and were ameliorated after ULT. Thus, MU could be a useful tool in assessing bone remodelling and monitoring disease responsiveness.

Analysis of the effect of metal ions on the ability of Xylanase to hydrolyze wheat bran by molecular dynamics simulations.

Introduction: Wheat bran is the main by-product of wheat processing, containing about 30% pentosan and 0.4%-0.7% ferulic acid. Wheat bran is the main raw material used to prepare feruloyl oligosaccharides by hydrolysis of Xylanase, we discovered that the ability of Xylanase to hydrolyze wheat bran could be affected in the presence of different metal ions. Methods: In the present study, we have probed the effects of different metal ions on the hydrolysis activity of Xylanase on wheat bran and tried to analyze the effect of Mn2+ and Xylanase by molecular dynamic (MD) simulation. Results: Our results suggested that Mn2+ had improved the Xylanase hydrolyzing wheat bran to obtain feruloyl oligosaccharides. Particularly when the concentration of Mn2+ reached 4 mmol/L, the optimal product has been obtained 2.8 times higher to compare with no addition. Through the MD simulation analysis, our results reveal that Mn2+ can induce structural change in the active site, which enlarges the substrate binding pocket. The simulation results also revealed that the addition of Mn2+ resulted in a low RMSD value compared with the absence of Mn2+ and helped stabilize the complex. Conclusion: Mn2+ could increase the enzymatic activity of Xylanase in the hydrolysis of feruloyl oligosaccharides in wheat bran. The finding could have significant implications for the preparation of feruloyl oligosaccharides from wheat bran.

Saak Transform-Based Machine Learning for Light-Sheet Imaging of Cardiac Trabeculation.

OBJECTIVE: Recent advances in light-sheet fluorescence microscopy (LSFM) enable 3-dimensional (3-D) imaging of cardiac architecture and mechanics in toto. However, segmentation of the cardiac trabecular network to quantify cardiac injury remains a challenge. METHODS: We hereby employed "subspace approximation with augmented kernels (Saak) transform" for accurate and efficient quantification of the light-sheet image stacks following chemotherapy-treatment. We established a machine learning framework with augmented kernels based on the Karhunen-Loeve Transform (KLT) to preserve linearity and reversibility of rectification. RESULTS: The Saak transform-based machine learning enhances computational efficiency and obviates iterative optimization of cost function needed for neural networks, minimizing the number of training datasets for segmentation in our scenario. The integration of forward and inverse Saak transforms can also serve as a light-weight module to filter adversarial perturbations and reconstruct estimated images, salvaging robustness of existing classification methods. The accuracy and robustness of the Saak transform are evident following the tests of dice similarity coefficients and various adversary perturbation algorithms, respectively. The addition of edge detection further allows for quantifying the surface area to volume ratio (SVR) of the myocardium in response to chemotherapy-induced cardiac remodeling. CONCLUSION: The combination of Saak transform, random forest, and edge detection augments segmentation efficiency by 20-fold as compared to manual processing. SIGNIFICANCE: This new methodology establishes a robust framework for post light-sheet imaging processing, and creating a data-driven machine learning for automated quantification of cardiac ultra-structure.

[Risk factors for mortality in intensive care unit patients with sepsis combined with acute kidney injury after continuous renal replacement therapy: secondary analysis of the data from a multicenter observational study].

OBJECTIVE: To analyze the risk factors of death in intensive care unit (ICU) patients with sepsis and acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). METHODS: The data of patients with sepsis complicated with AKI who received CRRT treatment from March 1st to August 31st in 2012 in BAKIT study (a prospective observational study of AKI epidemiology in 30 ICUs of 28 hospitals in Beijing) were re-analyzed. The demographic data, clinical and laboratory data of patients were collected, including gender, age, case source, body mass index (BMI), blood pressure, the length of ICU stay, complications, other organs' function, drug use, CRRT, mechanical ventilation and vasoactive drugs. Acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA) were calculated by the worst value of the index within 24 hours of entry into ICU. The end point of observation was to ICU mortality. All test factors were analyzed by single factor analysis, and then multivariate Logistic regression analysis was carried out for the parameters with statistical significance in single factor analysis. Risk factors affecting CRRT in ICU sepsis patients with AKI were screened. RESULTS: A total of 189 patients were enrolled, 103 of whom died, with a mortality rate of 54.50%. Compared with the survival group, the death group had an older age [years old: 77(67, 83) vs. 58 (39, 73)], a higher proportion of ICU entry due to respiratory diseases (55.40% vs. 38.37%), a higher proportion of complications such as grade IV of cardiac function, hypertension, coronary heart disease, chronic kidney disease (with renal insufficiency; 20.39% vs. 3.49%, 53.40% vs. 34.88%, 40.78% vs.10.47%, 20.39% vs. 9.30%, respectively), a longer the length of ICU stay [days: 8 (5, 19) vs. 13 (7, 22)], a higher APACHE II and SOFA scores (27.53±8.59 vs. 22.73±8.36, 12.22±4.00 vs. 9.51±4.49), a lower mean arterial pressure (MAP) valley value [mmHg (1 mmHg = 0.133 kPa): 65.36±19.52 vs. 71.60±17.92], a higher proportion of invasive mechanical ventilation (80.58% vs. 65.12%), high proportion of CRRT treatment due to hyperkalemia and severe metabolic acidosis (28.16% vs. 9.30%, 63.11% vs. 22.09%), and the time from ICU entry to CRRT initiation was longer [days: 1 (0, 5) vs. 1 (0, 2)], which differences were statistically significant (all P < 0.05). Logistic regression analysis showed that age, APACHE II, SOFA, MAP, grade IV of cardiac function, coronary heart disease and hyperkalemia were risk factors for death in ICU sepsis patients with AKI treated by CRRT. Age, APACHE II, SOFA and grade IV of cardiac function were independent risk factors [age: odds ratio (OR) = 1.054, 95% confidence interval (95%CI) = 1.032-1.077, P < 0.001; APACHE II: OR = 1.061, 95%CI = 1.021-1.102, P = 0.034; SOFA: OR = 1.078, 95%CI = 1.033-1.116, P = 0.042; grade IV of cardiac function: OR = 3.357, 95%CI = 0.884-12.747, P = 0.045]. CONCLUSIONS: Age, APACHE II, SOAF and grade IV of cardiac function were independent risk factors for death in ICU sepsis patients with AKI treated with CRRT. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-ONC-11001875.