Marginal and internal fit of 3D printed resin graft substitutes mimicking alveolar ridge augmentation: An in vitro pilot study.

Recent improvements in additive manufacturing technologies may facilitate the use of customized 3D printed grafts for horizontal and vertical augmentation of the atrophic alveolar ridge. The accurate fit of such grafts could reduce the clinical treatment time and contribute optimal bone regeneration. The aim of this in vitro study was to evaluate the marginal and internal fit of 3D printed resin grafts as they could be used for alveolar ridge augmentation. Alveolar ridge morphologic data were derived from the Cone Beam Computed Tomography (CBCT) scans of six patients with alveolar bone defects. These data were transferred to a segmentation program to produce virtual 3D reconstructions of the alveolar ridge models. Using a Computer Aided Design (CAD) program, the alveolar bone defects were defined and customized grafts were designed and both the defects as well as the grafts generated (CAM) as 3D projects. These projects were imported into a 3D printer and were manufactured in resin. Hereafter, the grafts were fitted to the defect sites of the corresponding models and new CBCT scans were performed. Based on these scans, measurements were made at the marginal and internal part of the fitted grafts to evaluate the marginal and internal fit, respectively. The statistical analysis revealed that the mean marginal fit was significantly better (P < 0.05) than the mean internal fit. The fit of the grafts was dependent on the shape and on the size of the grafts. Specifically, the total void surface between the fitted graft and the corresponding defect site was significantly larger in the large-defect grafts than the small-defect grafts (P < 0.05). Within the limitations of the study, it could be demonstrated that it is possible to fabricate 3D printed resin grafts with acceptable fit in customized shapes, when combining CBCT scans and computer aided design and 3D printing techniques

Serum hepcidin levels are associated with serum triglycerides and interleukin-6 concentrations in patients with end-stage renal disease

Hepcidin has emerged as a peptide with a key role in the regulation of iron homeostasis in patients with chronic kidney disease (CKD), having a strong dependence on inflammation. Recent studies reveal that hepcidin may be also associated with the progression of atherosclerosis. This study was performed to analyze the relation of hepcidin to markers of atherosclerosis and inflammation in patients on dialysis. A total of 90 individuals were enrolled. Sixty patients with end-stage renal disease, who were on hemodialysis (HD) (N=30) and peritoneal dialysis (N=30) were compared with 30 normal controls (NC). Age, body mass index, time on dialysis, serum lipids, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured and analyzed in correlation with hepcidin concentration. It was found that patients on HD and peritoneal dialysis have significantly higher (P&lt;0.0001) levels of hepcidin, CRP and IL-6 than NC. Hepcidin in dialysis patients is significantly related to age (r=0.373, P=0.012), serum triglycerides (r=0.401, P=0.005), HDL-C (r=-0.268, P=0.048), CRP (r=0.436, P=0.0007) and IL-6 (r=0.569, P&lt;0.0001). In multiple regression analysis, hepcidin correlated independently with triglycerides (β=0.402, P=0.041) and IL-6 (β=0.559, P=0.006). Moreover, patients with high triglycerides in combination with high IL-6 levels have significantly increased concentrations of hepcidin than those with low triglycerides and low IL-6 levels (P&lt;0.0001). Elevated levels of hepcidin in patients with CKD on dialysis may be related to the occurrence of high triglycerides and high IL-6 serum concentrations. This probably suggests that hepcidin may play a role to the progression of atherosclerosis and inflammation, but this hypothesis should be further evaluated. © 2013 International Society for Apheresis

Anti-Müllerian Hormone Concentrations Are Inversely Associated With Subclinical Atherosclerosis in Premenopausal Women

Anti-Müllerian hormone (AMH), which is secreted by granulosa cells of late preantral and small antral follicles, is a marker of ovarian reserve. The association of ovarian reserve with subclinical atherosclerosis in women of reproductive age is currently unknown. We primary investigated whether AMH levels are associated with markers of subclinical atherosclerosis in healthy, normally menstruating women. In this cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima–media thickness (IMT), flow-mediated dilation, carotid–femoral pulse wave velocity and augmentation index. Lipid profile and serum AMH concentrations were also measured. Seventy premenopausal women, aged 32.7 ± 6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and femoral and carotid IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or established cardiovascular (CV) risk factors was found. After multivariable adjustment, the association between AMH concentrations and combined carotid IMT or carotid bulb IMT remained significant. In conclusion, in healthy, normally ovulating women, AMH concentrations are negatively associated with subclinical atherosclerosis indices and TC levels, independently of established CV risk factors. © The Author(s) 2020

Subclinical atherosclerosis and vascular stiffness in premenopausal women: association with NOS3 and CYBA polymorphisms

Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS) and the NADH/NADPH oxidase system are related with atherosclerosis in the general population, but their significance in women is not sufficiently assessed. We investigated the potential association between the G894T polymorphism of the NOS3 gene and the C242T polymorphism of the CYBA gene with subclinical vascular disease. Seventy (70) healthy, normally ovulating, premenopausal women were recruited for this study. Venous blood samples were obtained for biochemical/hormonal assessment as well as for genotyping, using real-time PCR. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD), carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3% (38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4% (22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After multivariable adjustment, the hC242T polymorphism was a predictor of both internal carotid IMT (b-coefficient − 0.119, p = 0.011) and combined-IMT (b-coefficient − 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T determined values of FMD (b-coefficient − 1.604, p = 0.034). Concerning the NOS3 G894T polymorphism, carriers of the polymorphic variant had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis. In healthy premenopausal women, the CYBA C242T polymorphism is an independent determinant of endothelial function and subclinical atherosclerosis of the carotid arteries. The NOS3 G894T polymorphic variant also correlated with atherosclerosis, an association probably mediated by the traditional risk factors for CVD. The relevance of these findings in the clinical setting remains to be elucidated. © 2018, Springer Japan KK, part of Springer Nature

Controversial role of toll-like receptor 4 in adult stem cells

Adult or somatic stem cells are tissue-resident cells with the ability to proliferate, exhibit self-maintenance as well as to generate new cells with the principal phenotypes of the tissue in response to injury or disease. Due to their easy accessibility and their potential use in regenerative medicine, adult stem cells raise the hope for future personalisable therapies. After infection or during injury, they are exposed to broad range of pathogen or damage-associated molecules leading to changes in their proliferation, migration and differentiation. The sensing of such damage and infection signals is mostly achieved by Toll-Like Receptors (TLRs) with Toll-like receptor 4 being responsible for recognition of bacterial lipopolysaccharides (LPS) and endogenous danger-associated molecular patterns (DAMPs). In this review, we examine the current state of knowledge on the TLR4-mediated signalling in different adult stem cell populations. Specifically, we elaborate on the role of TLR4 and its ligands on proliferation, differentiation and migration of mesenchymal stem cells, hematopoietic stem cells as well as neural stem cells. Finally, we discuss conceptual and technical pitfalls in investigation of TLR4 signalling in stem cells