Effects of Vascular Aging on Murine and Human Hemodynamics Revealed by Computational Modeling: Applications to Hypertension Research

Aging is a primary risk factor for increased central arterial stiffness which is both an initiator and indicator of cardiovascular, neurovascular and renovascular disease. It is hypothesized that an insidious positive feedback loop exists between arterial stiffness and systemic blood pressure. The clinical measurement to assess arterial stiffness non-invasively is carotid to femoral Pulse Wave Velocity (cf-PWV), yet controversy still remains. There exists a need to evaluate cf-PWV as an early diagnostic of progressive vascular stiffening and to better assess the potential effects of regional variations in central mechanical properties on blood hemodynamics that adversely affect microcirculation in the heart, brain and kidneys. Computational modeling is a powerful tool to understand the complexity of central arterial function. In this work we used a robust, data-driven computational framework that combines 3D geometric vascular models, Fluid-Structure Interaction (FSI) analyses, Windkessel models to represent the distal vasculature and an external tissue boundary condition to represent perivascular support. FSI methods allowed to account for the deformability of the central vessels and included spatially variable anisotropic tissue properties. We first introduced a data-driven FSI computational model of the human aorta to simulate effects of aging-related changes in regional wall properties and geometry on several metrics of arterial stiffness. Using the best available biomechanical data, our results for PWV compared well to findings reported for large population studies while rendering a higher resolution description of evolving metrics of aortic stiffening. Our results revealed similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Furthermore, our analysis highlighted the importance of the tethering exerted by external tissues. Due to difficulty in obtaining detailed information on evolving regional mechanical properties in humans, we focused on mouse models of vascular aging, which offer the advantage of easier longitudinal studies and data accessibility. We developed a workflow to combine in vivo and in vitro biomechanical data to build mouse-specific computational models of the central vasculature. These FSI models are informed by micro-CT imaging, in vitro mechanical characterization of the arterial wall, and in vivo ultrasound and pressure measurements. We reproduced central artery biomechanics in adult wild-type, fibulin-5 deficient mice, a model of early vascular aging, and naturally aged wild type mice. Findings were also examined as a function of sex. Computational results compared well with data available in the literature and suggested that PWV does not well reflect the presence of regional differences in stiffening and it is affected by vascular wall stiffness heterogeneities. Modeling is also useful for evaluating quantities that are difficult to measure experimentally, including local pulse pressures at the renal arteries and characteristics of the peripheral vascular bed that may be altered by disease. Notwithstanding the many advantages of animal models, it is important to consider that invasive experimental procedures may alter the quantity of interest. Advanced computational models offer a unique method to evaluate these measurements. Herein we evaluated the effects of commercially available catheters on the very parameters that they are designed to measure, namely murine blood pressure and PWV. We investigated two different setups and observed that both alter the measured values of PWV. Lastly, we showed preliminary results involving automatic parameter estimation and expansion of the FSI framework to account for the large motions imposed by the heart on the aorta.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/150057/1/cuomofed_1.pdfDescription of cuomofed_1.pdf : Restricted to UM users only

analysis of a data flow in a financial iot system

Abstract Data retrieving, analysis e management are usually known as complex task in financial contexts. In an Internet of Things (IoT) system data-flow processes represent the knowledge base used in mathematical models for credits and financial products. Several sources such as distributed database systems, portals and local information are generally used as input of inferring models. In this paper we describe an overview of software tools, methodologies and strategies in real data-flow system

Adaptive mitigation of the Air-Time pressure in LoRa multi-gateway architectures

LoRa is a promising technology in the current Internet of Things market, which operates in un-licensed bands achieving long-range communications and with ultra power devices. In this work we capitalize on the idea introduced in [1], i.e. balance the Air-Time of the different modulation spreading factors (SF), and adapt it to operate in a typical metropolitan scenario comprising multiple gateways (GWs) interconnected to a same network server. Our proposed approach, named ADaptive Mitigation of the AIr-time pressure in lORa (AD MAIORA), relies on a suitable measure of the per-spreading-factor load at each GW - quantified by means of a so-called pressure table -, and on a relevant heuristic algorithm which attempts to balance such a per-SF-pressure. Especially in cases of very loaded scenarios, where a high number of nodes insist on the same GWs, the use of AD MAIORA shows significant performance gains, up to a factor of 5 improvements with respect to the legacy LoRaWAN's Adaptive Data Rate

Problematic internet use among high school students: Prevalence, associated factors and gender differences

This study aimed to measure the prevalence of Problematic Internet Use (PIU) among high school students and to identify factors associated with PIU underlining gender differences. The students filled a self-administered, anonymous questionnaire collecting information on demographic characteristics and patterns of Internet use. Multiple logistic regression analysis was performed to identify factors associated with PIU in the overall sample and by gender. Twenty-five schools and 2022 students participated in the survey. Prevalence of PIU was 14.2% among males and 10.1% among females. Males 15-year-olds and females 14-year-olds had the highest PIU prevalence that progressively lowered with age among females. Only 13.5% of pupils declared parents controlled their Internet use. The sensation of feeling lonely, the frequency of use, the number of hours of connection, and visiting pornographic websites were associated with the risk of PIU in both genders. Attending vocational schools, the activities of chatting and file downloading, and the location of use at Internet point among males, and younger age among females were associated with PIU, whilst information searching was protective among females. PIU could become a public health problem in the next years. The physical and mental health consequences should be studied

Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling

Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group

Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling

Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group.</p

The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs) are exclusively present on the biliary tract. Importantly, the GH-IGF-SST system components have been indicated as regulators of hepatocarcinogenesis. Reduction of GH binding affinity to GH receptor, decreased serum IGF1 and increased serum IGF2 production, overexpression of IGF1 receptor, loss of function of IGF2 receptor and appearance of SSTRs are frequently observed in human HCC. In particular, recently, many studies have evaluated the correlation between increased levels of IGF1 receptors and liver diseases and the oncogenic role of IGF2 and its involvement in angiogenesis, migration and, consequently, in tumour progression. SST directly or indirectly influences tumour growth and development through the inhibition of cell proliferation and secretion and induction of apoptosis, even though SST role in hepatocarcinogenesis is still opened to argument. This review addresses the present evidences suggesting a role of the GH-IGF-SST system in the development and progression of HCC, and describes the therapeutic perspectives, based on the targeting of GH-IGF-SST system, which have been hypothesised and experimented in HCC

Reduction of the microbial load in meat maturation rooms with and without alkaline electrolyzed water fumigation

Dry-aging is a process during which meat is stored within maturation chambers at low temperatures and low relative humidity, resulting in improved tenderness and flavor development. The cuts are exposed to the atmosphere by hanging them or setting them on racks in the maturation chamber without any protective packaging. Animals and humans are usually the major sources of bacterial food contamination in the meat industry, but other routes might be involved. Therefore, procedures to reduce or eliminate pathogens from surfaces are crucial for an effective hazard analysis critical control point program in the food industry and other environments. This study aimed to assess the survival of Listeria monocytogenes, Escherichia coli, Salmonella spp., and Staphylococcus aureus on the inner surface of dry aging chambers. Moreover, we tested the efficacy of alkaline electrolyzed water (REW) for its eventual application within a procedure aimed at reducing foodborne pathogens during meat storage. Environmental conditions inside the dry aging cabinet determine a reduction of circa 3 log CFU/cm2 of the considered microorganisms on the inner surface in 24 hours. Additionally, the nebulization of alkaline electrolyzed water with the smoking system increased the count reduction in 24 hours due to environmental conditions for L. monocytogenes (~1 log CFU/cm2) and for S. aureus (~2 log CFU/cm2). In this context, the use of REW can be justified for routine cleaning procedures of the surfaces, with the added value of being safe to handle, not containing environmental pollutants, and making it unnecessary to rinse surfaces due to its instability