Charles University in Prague

About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.

Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey

Abstract: Background: Fabry disease is a rare X-linked lysosomal storage disorder characterised by severe multisystemic involvement that leads to major organ failure and premature death in affected men and women. Over the past 7 years, the Fabry Outcome Survey (FOS) has collected data on the natural history of Fabry disease, and the long-term efficacy and safety of enzyme-replacement therapy. This paper provides an update on the first analysis of FOS data. Design: Baseline data on clinical manifestations and causes of death in a cohort of 1453 patients (699 male, 754 female) from 19 countries worldwide were analysed. Causes of death of affected relatives were analysed separately. Results: The most frequently reported signs and symptoms of Fabry disease were neurological. Cardiac, ocular, gastrointestinal, dermatological, auditory and renal manifestations were also common. The principal causes of death among 181 affected relatives of patients in FOS (most of whom had died before 2001) were renal failure in males (42%) and cerebrovascular disease in females (25%). In contrast, of the 42 patients enrolled in FOS whose deaths were reported between 2001 and 2007, cardiac disease was the main cause of death in both male (34%) and female (57%) patients. Conclusion: These data suggest that the importance of renal disease as a cause of death in patients with Fabry disease is decreasing while the importance of cardiac disease is increasing. This pattern probably reflects improvements in the management of renal disease in patients with Fabry disease.

Tubal ligation and the risk of ovarian cancer: review and meta-analysis

Abstract: background: The reduction of ovarian cancer (OC) risk in women with a history of tubal ligation (TL) has been reported repeatedly, mostly on small populations. We have aimed to provide a critical overview of the studies available to date and to conduct a meta-analysis. methods: There were 40 relevant studies identified. The studies were divided into two groups for strict and extended meta-analysis, respect- ively. Subgroup analysis was performed for age, time dependency since TL, histological types of OC and BReast CAncer (BRCA) mutation. results: Meta-analysis of 13 strictly selected studies showed a reduced risk of epithelial OC by 34%. The protective effect of TL was confirmed even in a subgroup of women 10-14 years after the procedure. The risk reduction was confirmed for the endometrioid (RR ¼ 0.40) and serous (RR ¼ 0.73) cancers but not for mucinous. conclusions: The review of relevant articles, as well as the meta-analysis of selected studies, yields consistent data on a significant reduction of OC risk in women who had undergone TL. The results of this meta-analysis should provide an impulse for further research on the etiology of ovarian epithelial cancers, focusing particularly on the importance of retrograde transport of endometrial cells.

Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer

Abstract: The primary objective of Tissue engineering is a regeneration or replacement of tissues or organs damaged by disease, injury, or congenital anomalies. At present, Tissue engineering repairs damaged tissues and organs with artificial supporting structures called scaffolds. These are used for attachment and subsequent growth of appropriate cells. During the cell growth gradual biodegradation of the scaffold occurs and the final product is a new tissue with the desired shape and properties. In recent years, research workplaces are focused on developing scaffold by bio-fabrication techniques to achieve fast, precise and cheap automatic manufacturing of these structures. Most promising techniques seem to be Rapid prototyping due to its high level of precision and controlling. However, this technique is still to solve various issues before it is easily used for scaffold fabrication. In this article we tested printing of clinically applicable scaffolds with use of commercially available devices and materials. Research presented in this article is in general focused on “scaffolding” on a field of bone tissue replacement. Commercially available 3D printer and Polylactic acid were used to create originally designed and possibly suitable scaffold structures for bone tissue engineering. We tested printing of scaffolds with different geometrical structures. Based on the osteosarcoma cells proliferation experiment and mechanical testing of designed scaffold samples, it will be stated that it is likely not necessary to keep the recommended porosity of the scaffold for bone tissue replacement at about 90%, and it will also be clarified why this fact eliminates mechanical properties issue. Moreover, it is demonstrated that the size of an individual pore could be double the size of the recommended range between 0.2–0.35 mm without affecting the cell proliferation. Rapid prototyping technique based on Fused deposition modelling was used for the fabrication of designed scaffold structures. All the experiments were performed in order to show how to possibly solve certain limitations and issues that are currently reported by research workplaces on the field of scaffold bio-fabrication. These results should provide new valuable knowledge for further research.

Genetic modifiers of liver disease in cystic fibrosis.

Abstract: Context A subset (≈ 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (α1-antitrypsin or α1-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor β1 [TGFB1]) are associated with severe liver disease in patients with CF. Design, Setting, and Participants Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site. In the initial study, 124 patients with CFLD (enrolled January 1999-December 2004) and 843 control patients without CFLD were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 patients with CFLD (enrolled January 2005-February 2007) and 1088 with no CFLD. Main Outcome Measures Differences in distribution of genotypes in patients with CFLD vs patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 Z allele (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.31-9.61; P = 3.3 × 10−6) and with TGFB1 codon 10 CC genotype (OR, 1.53; 95% CI, 1.16-2.03; P = 2.8 × 10−3). In the replication study, CFLD was associated with the SERPINA1 Z allele (OR, 3.42; 95% CI, 1.54-7.59; P = 1.4 × 10−3) but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (OR, 5.04; 95% CI, 2.88-8.83; P = 1.5 × 10−8). Conclusions The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater risk (OR, ≈ 5) of developing severe liver disease with portal hypertension.

Thermal skyrmion diffusion used in a reshuffler device

Abstract: Magnetic skyrmions in thin films can be efficiently displaced with high speed by using spin-transfer torques1,2 and spin–orbit torques3–5 at low current densities. Although this favourable combination of properties has raised expectations for using skyrmions in devices6,7, only a few publications have studied the thermal effects on the skyrmion dynamics8–10. However, thermally induced skyrmion dynamics can be used for applications11 such as unconventional computing approaches12, as they have been predicted to be useful for probabilistic computing devices13. In our work, we uncover thermal diffusive skyrmion dynamics by a combined experimental and numerical study. We probed the dynamics of magnetic skyrmions in a specially tailored low-pinning multilayer material. The observed thermally excited skyrmion motion dominates the dynamics. Analysing the diffusion as a function of temperature, we found an exponential dependence, which we confirmed by means of numerical simulations. The diffusion of skyrmions was further used in a signal reshuffling device as part of a skyrmion-based probabilistic computing architecture. Owing to its inherent two-dimensional texture, the observation of a diffusive motion of skyrmions in thin-film systems may also yield insights in soft-matter-like characteristics (for example, studies of fluctuation theorems, thermally induced roughening and so on), which thus makes it highly desirable to realize and study thermal effects in experimentally accessible skyrmion systems. Thermal diffusion of skyrmions in a non-flat energy landscape shows exponential temperature dependence and can be used for a reshuffler device with potential application in probabilistic computing.