Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis

ObjectivesPathways contributing to endothelial dysfunction in patients with limited cutaneous systemic sclerosis (lcSSc) are largely unknown. The aim of this study was to investigate potential associations of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathy-related changes in patients with lcSSc and early-stage vasculopathy.MethodsAmino acids, calciotropic parameters, including 25-hydroxyvitamin D and parathyroid hormone (PTH), and bone turnover parameters, including osteocalcin and N-terminal peptide of procollagen-3 (P3NP), were measured in 38 lcSSc patients and 38 controls. Endothelial dysfunction was assessed by biochemical parameters, pulse-wave analysis, flow-mediated and nitroglycerine-mediated dilation. Additionally, vasculopathy-related and SSc-specific clinical changes including capillaroscopic, skin, renal, pulmonary, gastrointestinal and periodontal parameters were recorded.ResultsNo significant differences in amino acids, calciotropic and bone turnover parameters were observed between lcSSc patients and controls. In patients with lcSSc, several significant correlations were found between selected amino acids, parameters of endothelial dysfunction, vasculopathy-related and SSc-specific clinical changes (all with p < 0.05). In addition, significant correlations were observed between PTH and 25-hydroxyvitamin D with homoarginine, and between osteocalcin, PTH and P3NP with modified Rodnan skin score and selected periodontal parameters (all with p < 0.05). Vitamin D deficiency defined as 25-hydroxyvitamin D < 20 ng/ml was associated with the presence of puffy finger (p = 0.046) and early pattern (p = 0.040).ConclusionSelected amino acids may affect endothelial function and may be associated to vasculopathy-related and clinical changes in lcSSc patients, while the association with parameters of bone metabolism seems to be minor

TNF-α suppresses the expression of clock genes by interfering with E-box-mediated transcription

Production of TNF-α and IL-1 in infectious and autoimmune diseases is associated with fever, fatigue, and sleep disturbances, which are collectively referred to as sickness behavior syndrome. In mice TNF-α and IL-1 increase nonrapid eye movement sleep. Because clock genes regulate the circadian rhythm and thereby locomotor activity and may alter sleep architecture we assessed the influence of TNF-α on the circadian timing system. TNF-α is shown here to suppress the expression of the PAR bZip clock-controlled genes Dbp, Tef, and Hlf and of the period genes Per1, Per2, and Per3 in fibroblasts in vitro and in vivo in the liver of mice infused with the cytokine. The effect of TNF-α on clock genes is shared by IL-1β, but not by IFN-α, and IL-6. Furthermore, TNF-α interferes with the expression of Dbp in the suprachiasmatic nucleus and causes prolonged rest periods in the dark when mice show spontaneous locomotor activity. Using clock reporter genes TNF-α is found here to inhibit CLOCK-BMAL1-induced activation of E-box regulatory elements-dependent clock gene promoters. We suggest that the increase of TNF-α and IL-1β, as seen in infectious and autoimmune diseases, impairs clock gene functions and causes fatigue

Autonomous Free-Form Trenching using a Walking Excavator

ISSN:2377-376

Meniscus sizing using three-dimensional models of the ipsilateral tibia plateau based on CT scans - an experimental study of a new sizing approach

PURPOSE Selection of a meniscus allograft with a similar three-dimensional (3D) size is essential for good clinical results in meniscus allograft surgery. Direct meniscus sizing by MRI scan is not possible in total meniscectomy and indirect sizing by conventional radiography is often inaccurate. The purpose of this study was to develop a new indirect sizing method, based on the 3D shape of the ipsilateral tibia plateau, which is independent of the meniscus condition. METHODS MRI and CT scans of fifty healthy knee joints were used to create 3D surface models of both menisci (MRI) and tibia plateau (CT). 3D bone models of the proximal 10 mm of the entire and half tibia plateau (with / without intercondylar area) were created in a standardized fashion. For each meniscus, the best fitting "allograft" couple out of all other 49 menisci were assessed by the surface distance of the 3D meniscus (best available allograft), of the 3D tibia plateau (3D-CT) and by the radiographic method of Pollard (2D-RX). RESULTS 3D-CT sizing was significantly better by using only the half tibia plateau without the intercondylar area (p < 0.001). But neither sizing by 3D-CT, nor by 2D-RX could select the best available allograft. Compared to 2D-RX, 3D-CT sizing was significantly better for the medial, but not for the lateral meniscus. CONCLUSIONS Automatized, indirect meniscus sizing using the 3D bone models of the tibia plateau is feasible and more precise than the previously described 2D-RX method.. However, further technical improvement is needed to select always the best available allograft

Three-dimensional meniscus allograft sizing - a study of 280 healthy menisci

Background: Inaccurate meniscus allograft size is still an important problem of the currently used sizing methods. The purpose of this study was to evaluate a new three-dimensional (3D) meniscus-sizing method to increase the accuracy of the selected allografts. Methods: 3D triangular surface models were generated from 280 menisci based on 50 bilateral and 40 unilateral knee joint magnetic resonance imaging (MRI) scans. These models served as an imaginary meniscus allograft tissue bank. Meniscus sizing and allograft selection was simulated for all 50 bilateral knee joints by (1) the closest mean surface distance (MeSD) (3D-MRI sizing with contralateral meniscus), (2) the smallest meniscal width/length difference in MRI (2D-MRI sizing with contralateral meniscus), and (3) conventional radiography as proposed by Pollard (2D-radiograph (RX) sizing with ipsilateral tibia plateau). 3D shape and meniscal width, length, and height were compared between the original meniscus and the selected meniscus using the three sizing methods. Results: Allograft selection by MeSD (3D MRI) was superior for all measurement parameters. In particular, the 3D shape was significantly improved (p < 0.001), while the mean differences in meniscal width, length, and height were only slightly better than the allograft selected by the other methods. Outliers were reduced by up to 55% (vs. 2D MRI) and 83% (vs. 2D RX) for the medial meniscus and 39% (vs. 2D MRI) and 56% (vs. 2D RX) for the lateral meniscus. Conclusion: 3D-MRI sizing by MeSD using the contralateral meniscus as a reconstruction template can significantly improve meniscus allograft selection. Sizing using conventional radiography should probably not be recommended. Trial registration: Kantonale Ethikkommission Zürich had given the approval for the study (BASEC-No. 2018-00856

Intermediate-Term Outcome of 3-Dimensional Corrective Osteotomy for Malunited Distal Radius Fractures With a Mean Follow-Up of 6 Years

PURPOSE Our study aimed to analyze the functional and radiological intermediate-term outcome of 3-dimensional-guided corrective osteotomies for malunited distal radius fractures and to evaluate the progression of osteoarthritis after this intervention. METHODS All patients with malunited distal radius fractures who underwent 3-dimensional-guided corrective osteotomies from October 2008 to January 2015 were included. Pre- and postoperative range of motion, grip strength, and postoperative patient-reported outcomes were assessed. Pre- and postoperative osteoarthritis grading was performed using conventional radiographs and the osteoarthritis grading system described by Knirk and Jupiter. Additionally, the evaluation of articular stepoff was performed using pre- and postoperative computed tomography. RESULTS Fifteen patients, with a mean follow-up of 6 years (range, 4.1-10.4 years), were included. According to rater 1, 8 cases had no postoperative osteoarthritis progression, 6 cases had progression of 1 grade, and 1 case had progression of 2 grades. According to rater 2, there was no progression in 11 cases, and there was progression of 1 grade in 2 cases and progression of 2 grades in 2 cases. Compared with before the surgery, the patients demonstrated a mean improvement of 14.8 kg (±12.6 kg) in grip strength after the surgery. At the last follow-up, the mean Patient-Rated Wrist Evaluation score was 11.8 (±12.0), the mean Disabilities of the Arm, Shoulder and Hand score was 11.1 (±11.4), and the mean residual pain score on the visual analog scale was 0.8 (±1.0). CONCLUSIONS The intermediate-term outcome of 3-dimensional-guided corrective osteotomies for distal radius intra-articular malunions showed excellent patient-reported outcomes and no clinically relevant progression of osteoarthritis. Type of study/level of evidence Therapeutic IV