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Glycosylation is a crucial attribute for biotherapeutics with significant impacts on quality, stability, safety, immunogenicity, pharmacokinetics, and efficacy. Therefore, to ensure consistent glycosylation, a systematic review of biotherapeutics is absolutely required including the variable glycan structure (micro-heterogeneity) and different occupancy at individual site (macro-heterogeneity) from drug design to upstream and downstream bioprocesses. Various methods have been used for glyco-characterization of biotherapeutics at the glycan, glycopeptide, and intact protein levels. In particular, intact protein analysis is considered a facile and rapid glycoform monitoring approach used throughout the product development lifecycle to determine suitable glycosylation lead candidates and reproducible product quality. However, intact glycoform characterization of diverse and complex biotherapeutics with multiple N- and O-glycosylation sites can be very challenging. To address this, a robust analytical platform that enables rapid and accurate characterization of a biotherapeutics with highly complex multiple glycosylation using two-step intact glycoform mass spectrometry has been developed. We used darbepoetin alfa, a second-generation EPO bearing multiple N- and O-glycosylation sites, as a model biotherapeutics to obtain integrated information on glycan heterogeneity and site occupancy through step-by-step MS of intact protein and enzyme-treated protein. In addition, we performed a comparative assessment of the heterogeneity from different products, confirming that our new method can efficiently evaluate glycosylation equivalence. This new strategy provides rapid and accurate information on the degree of glycosylation of a therapeutic glycoprotein with multiple glycosylation, which can be used to assess glycosylation similarity between batches and between biosimilar and reference during development and production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: While inflammation is associated with obesity and insulin resistance, their inter-relationships in the development of type 2 diabetes or hypertension are not clear., Aim of the Study: To evaluate inflammatory markers in prediction of type 2 diabetes and hypertension., Methods: The study population of this retrospective cohort study consisted of individuals who participated in a comprehensive health screening program with measurement of white blood cell count and C-reactive protein from 2002-2010 (N = 96,606) in nondiabetic and normotensive Koreans. Median follow up time were 3.7 years for incident type 2 diabetes and 3.3 years for hypertension. Multivariate Cox proportional hazards models were performed to assess risk for type 2 diabetes or hypertension by white blood cell or C-reactive protein quartiles with adjustment of various possible confounding factors including insulin resistance., Results: During the follow-up period, 1448 (1.5%) developed type 2 diabetes and 10,405 (10.8%) developed hypertension. Among men, comparison of adjusted hazard ratios (HR) for incident type 2 diabetes in the highest versus lowest white blood cell or C-reactive protein quartiles were 1.48 [95% confidence interval (CI), 1.20-1.83] and 1.30 (95% CI, 1.07-1.57), respectively. Among women, white blood cell but not C-reactive protein was significantly associated with type 2 diabetes [HR 1.79 (95% CI 1.24-2.57)]. White blood cell and C-reactive protein quartiles were also modestly associated with incident hypertension in both sexes., Conclusions: Although white blood cell and C-reactive protein are associated with adiposity and insulin resistance, these inflammatory markers also independently predict type 2 diabetes and/or hypertension., (Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.)

Introduction: In this article, we aim to present our novel experience of bladder stone removal under pneumovesicoscopic field using a laparoscopic entrapment sac., Technical Considerations: We retrospectively reviewed the medical records of 21 patients who had pneumovesicoscopic bladder stone removal to assess a variety of patient characteristics and surgical outcomes. We considered stone burden, stone removal time including pneumovesicoscopic procedure time, postoperative catheter indwelling duration, postoperative hospital stay, and complications. The procedure was performed in the following steps: Under cystoscopy filled with saline solution, a 10-mm suprapubic transvesical trocar was inserted. After changing optical transmission medium from saline to CO(2) gas, pneumovesicoscopic procedure was performed to put stones in an entrapment sac inserted through the trocar. The stones trapped in the sac were extracorporeally broken with a lithotripter via the suprapubic route. The mean patient age was 58.95 ± 22.03 years. The mean stone burden was 4.88 ± 2.63 cm. Eleven patients had a single stone, whereas 10 had multiple stones. All stones were completely removed. The mean operative time was 31.66 ± 7.25 minutes, including the pneumovesicoscopic procedure time of 13.81 ± 7.30 minutes. In all but 6 patients with a cystostomy or a combined transurethral resection of the prostate, the urethra catheter was removed on the day after surgery; the mean postoperative hospital stay was 1.67 ± 0.49 days. There were 5 postoperative complications of Clavien grade I or II., Conclusion: We report the technical feasibility of pneumovesicoscopic bladder stone removal using a laparoscopic entrapment sac as a minimally invasive method. This technique will likely become more important as a useful option for treating bladder stones., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Low-dose computed tomography (CT) reduces radiation exposure but decreases signal-to-noise ratio (SNR) and diagnostic capabilities. Noise compensation can improve SNR so low-dose CT can provide valuable information for diagnosis without risking patient radiation exposure. In this study, a novel noise-compensated CT reconstruction method that uses spatially adaptive Monte-Carlo sampling to produce noise-compensated reconstructions is investigated. By adapting to local noise statistics, a non-parametric estimation of the noise-free image is computed that successfully handles non-stationary noise found in low-dose CT images. Using phantom and real low-dose CT images, effective noise suppression is shown to be accomplished while maintaining structures and details., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To determine and compare autonomic dysfunction in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Methods: The subjects were 30-60 years old and had no known systemic disease. Electrocardiographic signals in the patients in the resting state were obtained from 59 patients with CP/CPPS (age 46.5 ± 7.02 years) and 94 healthy subjects (age 48.4 ± 5.96 years), and heart rate variability parameters were compared., Results: The standard deviation of the N-N interval (P < .001), square root of the mean squared differences of the successive N-N intervals (P = .004), total power (P = .004), very low frequency (P = .012), and high frequency (P < .001) were lower in the patients with CP/CPPS. However, no significant differences were found in the low frequency and low frequency/high frequency ratios., Conclusion: Patients with CP/CPPS exhibited lower heart rate variability parameters compared with normal controls, with the exception of low frequency and low frequency/high frequency ratios. Possible differences in autonomic nervous system between those with CP/CPPS and normal healthy subjects could exist and autonomic dysfunction might be 1 of the causes that aggravates CP/CPPS., (Copyright © 2011 Elsevier Inc. All rights reserved.)