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Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies.

Aims: The aim of this paper is to develop a new, simple equation for deep spherical indentations.Background: The Hertzian theory is the most widely applied mathematical tool when testing soft materials because it provides an elementary equation that can be used to fit force-indentation data and determine the mechanical properties of the sample (i.e., its Young's modulus). However, the Hertz equation is only valid for parabolic or spherical indenters at low indentation depths. For large indentation depths, Sneddon's extension of the Hertzian theory offers accurate force-indentation equations, while alternative approaches have also been developed. Despite ongoing mathematical efforts to derive new accurate equations for deep spherical indentations, the Hertz equation is still commonly used in most cases due to its simplicity in data processing.Objective: The main objective of this paper is to simplify the data processing for deep spherical indentations, primarily by providing an accurate equation that can be easily fitted to force-indentation data, similar to the Hertzian equation.Methods: A simple power-law equation is derived by considering the equal work done by the indenter using the actual equation.Results: The mentioned power-law equation was tested on simulated force-indentation data created using both spherical and sphero-conical indenters. Furthermore, it was applied to experimental force-indentation data obtained from agarose gels, demonstrating remarkable accuracy.Conclusion: A new elementary power-law equation for accurately determining Young's modulus in deep spherical indentation has been derived.

Cancer cells have different characteristics from normal cells in terms of morphology, cell–cell interactions, cytoskeleton organization, cell growth rates, and cell-extracellular matrix interactions. Although the clarification of these characteristics is crucial for the effective development of new therapeutic strategies, they remain poorly identified. Furthermore, tumor microenvironment plays a crucial role in cancer progression and metastasis, and thus, it is of utmost importance to decode and fully understand the crosstalk and the interactions between its different components. Atomic force microscopy (AFM) is an established and multifunctional tool in biomedical sciences with many applications in cancer research. In this review, we discuss the use of AFM in the study of cancer cells and the tumor microenvironment. We first provide a brief overview of AFM operating principles highlighting its contribution to the study of cancer and stromal cells. Next, we present research on the use of AFM in the study of cell-tumor microenvironment interactions during cancer cell migration and invasion. Finally, we discuss the development of coupled AFM modalities and the combination of different kinds of imaging with AFM that have been applied to cancer research.

A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this work, a multilevel approach was employed to assess the implant-induced and biocorrosion-related inflammation in the adjacent vascular tissue using a mouse stent implantation model. The implications of biocorrosion on peri-implant tissue were assessed at the macroscopic level via in vivoimaging and histomorphology. Elevated matrix metalloproteinase activity, colocalized with the site of implantation, and histological staining indicated that stent surface condition and implantation time affect the inflammatory response and subsequent formation and extent of neointima. Hematological measurements also demonstrated that accumulated metal particle contamination in blood samples from corroded-stetted mice causes a stronger immune response. At the cellular level, the stent-induced alterations in the nanostructure, cytoskeleton, and mechanical properties of circulating lymphocytes were investigated. It was found that cells from corroded-stented samples exhibited higher stiffness, in terms of Young’s modulus values, compared to noncorroded and sham-stented samples. Nanomechanical modifications were also accompanied by cellular remodeling, through alterations in cell morphology and stress (F-actin) fiber characteristics. Our analysis indicates that surface wear and elevated metal particle contamination, prompted by corroded stents, may contribute to the inflammatory response and the multifactorial process of in-stent restenosis. The results also suggest that circulating lymphocytes could be a novel nanomechanical biomarker for peri-implant tissue inflammation and possibly the early stage of in-stent restenosis. Large-scale studies are warranted to further investigate these findings.

Background: Atomic Force Microscopy (AFM) Nanoindentation procedure regarding biological samples poses significant challenges with respect to the accuracy of the provided results. These challenges are related to the inhomogeneity of biological samples, various uncertainties in experimental methods and certain approximations regarding the theoretical analysis. The most commonly used theoretical model for data processing at the linear elastic regime regarding biological samples is the Hertz model. Objective: This paper focuses on the investigation of the resulting errors of the basic equation of the Hertz theory that depend on the ratio, indentation depth/indenter’s radius regarding the Young’s modulus calculation. Methods: An extended new equation is derived which takes into account the influence of the indentation depth/indenter’s radius ratio on the calculation of the Young’s modulus and can be easily used for calculations. The derived equation is further combined with equations which take into account the shape of the sample. Results: Several examples in the literature that do not take into account the value of the ratio indentation depth/indenter’s radius are reported and the related errors are calculated and discussed. Moreover, a rational explanation, regarding the extended differences of the Young’s modulus calculations using the same experimental results when these are processed using the Hertz model and the Oliver & Pharr analysis (which is the general model that applies for any axisymmetric indenter) is provided. Conclusion: A complete and reliable theoretical tool was developed (that takes into account the indentation depth/indenter’s radius ratio and the shape of the sample) which can be generally applied in order to reduce the errors produced by the current methodology (Hertz model).

Background: The determination of the mechanical properties of biological samples using Atomic Force Microscopy (AFM) at the nanoscale is usually performed using basic models arising from the contact mechanics theory. In particular, the Hertz model is the most frequently used theoretical tool for data processing. However, the Hertz model requires several assumptions, such as homogeneous and isotropic samples and indenters with perfectly spherical or conical shapes. As it is widely known, none of these requirements are 100 % fulfilled for the case of indentation experiments at the nanoscale. As a result, significant errors arise in the Young’s modulus calculation. At the same time, an analytical model that could account complexities of soft biomaterials, such as nonlinear behavior, anisotropy, and heterogeneity, may be far-reaching. In addition, this hypothetical model would be ‘too difficult’ to be applied in real clinical activities since it would require a very heavy workload and highly specialized personnel. Objective: In this paper, a simple solution is provided to the aforementioned dead-end. A new approach is introduced in order to provide a simple and accurate method for mechanical characterization at the nanoscale. Methods: The ratio of the work done by the indenter on the sample of interest to the work done by the indenter on a reference sample is introduced as a new physical quantity that does not require homogeneous, isotropic samples or perfect indenters. Results: The proposed approach provides an accurate solution from not only a physical perspective but also a simpler solution which does not require activities such as the determination of the cantilever’s spring constant and the dimensions of the AFM tip. Conclusion: It has been observed from this opinion paper that the solution aims to provide a significant opportunity to overcome the existing limitations provided by Hertzian mechanics and apply AFM techniques in real clinical activities.

Our century has been described as the electronic age and every day new technologies or applications, that generate data with exponential rates, are emerged. As a consequence, all and more organizations are facing the problem of managing large amounts of data. Generally, the large amount of data and their handling, storage and analysis is referred as Big Data. The emerging field of Big Data poses many challenges for healthcare organizations, as healthcare data and information increases. The paper describes the emerging era of Big Data in the field of health care and focuses on their benefits, challenges and ethics providing a broad overview for healthcare researchers, practitioners and health policy makers. Furthermore, we proposed a three-dimensional model for assessing Big Data concerns in the medical context. The paper is not intended to be a comprehensive review of the state-of-the-art of Big Data technology, but rather to raise the awareness of the considerations that healthcare professionals may face or will face in the near future.

The application of the AFM nanoindentation procedure in order to determine the Young's modulus values of specific nanoregions, results in many uncertainties, especially when biological samples are tested. This fact is due mainly to significant errors concerning the Young's modulus calculation because physical parameters such as the spring constant of the cantilever and the exact shape and size of the tip provide uncertainties. Thus, the objective of this paper was to introduce a more accurate and simple approach of the nanoindentation technique by introducing the relative differences of Young's modulus values. The new approach can be applied in measurements where the influence of a controlled external factor on a specific nanoregion is tested or variations in the mechanical properties of heterogeneous materials are investigated. The analysis was based on the general mathematical analysis which is used in the indentation procedure for the characterization of biological samples. The major advantage of the new technique is that it depends only on the cantilever's deflection - displacement curves which can be obtained with great accuracy. In addition, in order to provide full insight in the new technique, the mechanical heterogeneity of collagen was examined. As a conclusion, when a sample is tested under the influence of a controlled external factor, or when inhomogeneous samples are tested, the determination of the percentage variations of the Young's modulus is the most accurate parameter.

Collagen due to its filamentous shape and unique properties is a very promising molecule for the development of nanostructures, scaffolds, cell culture platforms and nanobiomaterials. Furthermore, collagen thin films are of great interest as they can cover non-biological surfaces in medical devices and sensors so as to offer them biocompatibility. Since surface nanotopography and mechanical properties can influence cell-biomaterial interactions it is of crucial importance to nano-characterize collagen surface and heterogeneity. Nano-characterization can be performed with Atomic Force Microscopy (AFM), which operates in a variety of modes/techniques and can offer a wide range of information, from topography to mechanical properties. In this paper it was sought to gain insights of structural and mechanical heterogeneity of collagen fibers in thin films by combining AFM multimode-imaging, including phase imaging, with quantitative measurements through nanoindentation. The results demonstrated that the overlap-gap regions on collagen fibers (D-periodicity) yield a significant phase contrast, due to different mechanical properties. In addition, phase contrast was also demonstrated in collagen 'kinks', which provides evidence that collagen fiber shell and core possess different properties. The mechanical heterogeneity of the collagen fibers in the kink areas was confirmed by AFM-nanoindentation and the obtained quantitative measurements. In addition, AFM multimode imaging performance was demonstrated on fibroblasts cultured on collagen thin films. The correlation between the heterogeneous structure and the mechanical properties of collagen fibers in thin films will enable the design and development of biomaterials and tissue scaffolds with improved properties.

Microalbuminuria (MA) is an independent risk factor for atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Postprandial lipemia is also associated with excess cardiovascular risk. However, the association between MA and postprandial lipemia in diabetes has not been investigated. A total of 64 patients with T2DM, 30 with and 34 without MA, were examined. Plasma total triglycerides (TGs), triglycerides contained in chylomicrons (CM-TG), and TGs in CM-deficient plasma were measured at baseline and every 2 h for 6 h after a mixed meal. Postheparin LPL and HL activities were also determined. Plasma levels of apolipoprotein A-V (apoA-V), apoC-II, and apoC-III were measured in the fasting state and 2 h postprandially. Patients with MA had higher postprandial total TG levels than those without MA (P < 0.001); this increase been attributed mainly to CM-TG. LPL activity and fasting concentrations of the measured apolipoproteins were not different between the studied groups, whereas HL activity was higher in the patients with MA. ApoC-II and apoC-III levels did not change postprandially in either study group, whereas apoA-V increased more in the patients with MA. These data demonstrate for the first time that MA is characterized by increased postprandial lipemia in patients with T2DM and may explain in part the excess cardiovascular risk in these patients.

Microalbuminuria (MA) is an independent risk factor for atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Postprandial lipemia is also associated with excess cardiovascular risk. However, the association between MA and postprandial lipemia in diabetes has not been investigated. A total of 64 patients with T2DM, 30 with and 34 without MA, were examined. Plasma total triglycerides (TGs), triglycerides contained in chylomicrons (CM-TG), and TGs in CM-deficient plasma were measured at baseline and every 2 h for 6 h after a mixed meal. Postheparin LPL and HL activities were also determined. Plasma levels of apolipoprotein A-V (apoA-V), apoC-II, and apoC-III were measured in the fasting state and 2 h postprandially. Patients with MA had higher postprandial total TG levels than those without MA (P< 0.001); this increase been attributed mainly to CM-TG. LPL activity and fasting concentrations of the measured apolipoproteins were not different between the studied groups, whereas HL activity was higher in the patients with MA. ApoC-II and apoC-III levels did not change postprandially in either study group, whereas apoA-V increased more in the patients with MA. These data demonstrate for the first time that MA is characterized by increased postprandial lipemia in patients with T2DM and may explain in part the excess cardiovascular risk in these patients.