The passive biomechanics of human pelvic collecting lymphatic vessels

The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport

Adaptive mechanisms of plants against salt stress and salt shock

Salinization process occurs when soil is contaminated with salt, which consequently influences plant growth and development leading to reduction in yield of many food crops. Responding to a higher salt concentration than the normal range can result in plant developing complex physiological traits and activation of stress-related genes and metabolic pathways. Many studies have been carried out by different research groups to understand adaptive mechanism in many plant species towards salinity stress. However, different methods of sodium chloride (NaCl) applications definitely give different responses and adaptive mechanisms towards the increase in salinity. Gradual increase in NaCl application causes the plant to have salt stress or osmotic stress, while single step and high concentration of NaCl may result in salt shock or osmotic shock. Osmotic shock can cause cell plasmolysis and leakage of osmolytes in plant. Also, the gene expression pattern is influenced by the type of methods used in increasing the salinity. Therefore, this chapter discusses the adaptive mechanism in plant responding to both types of salinity increment, which include the morphological changes of plant roots and aerial parts, involvement of signalling molecules in stress perception and regulatory networks and production of osmolyte and osmoprotective proteins

Investigation of wall shear stress related factors in realistic carotid bifurcation geometries and different flow conditions

Cardiovascular diseases are one of the major causes of death in the world; atherosclerosis being one aspect. Carotid bifurcation is one of the sites that are vulnerable to this disease. Wall Shear Stress (WSS) is known to be responsible for the process of atherogenesis. In this study, we have simulated the blood flow for Newtonian and non-Newtonian, steady and unsteady, flow conditions in three idealistic and five realistic geometries. A risk factor has been presented based on the results of wall shear stress and, then, a relation was found between geometrical features and the wall shear stress risk factor. Our main conclusions are: 1) The non-Newtonian behavior of blood elevates the value of wall shear stress, however, the wall shear stress pattern is similar, 2) The bifurcation angle is not the main cause of atherosclerosis and cannot be considered a predictor for atherosclerosis disease, and 3) The ratio of sinus diameter to the internal carotid artery diameter is more important than other geometrical factors, and the WSS pattern is influenced by this factor. © Sharif University of Technology, October 2010

Comparison effect of prescription drugs on the occurrence and the number of attacks in patients with multiple sclerosis

Background: Treatment has a major effect on attacks in patients with multiple sclerosis (MS). This study aimed to determine the effect of the type of used drug on occurrence and number of attacks in patients with multiple sclerosis. Methods: In this cross-sectional study, 1815 patients with multiple sclerosis referred to Ayatollah Kashani hospital in Isfahan, Iran, whose information was recorded in iMED software and followed at least for 34 months, were included. The effect of the type of drug on occurrence and number of attacks was determined using Negative Binomial Hurdle model by R software. Findings: The type of drug had a significant effect on the occurrence of attack; so that, compared to interferon beta-1a (muscle), interferon beta-1a (subcutaneous), fingolimod, glatiramer acetate and azathioprine were less effective, especially for relapsing-remitting types. Interferon beta-1b and glatiramer acetate had more and less effective on the occurrence of the attack in women and men, respectively. In women, fingolimod drugs, glatiramer acetate, and azathioprine had less effect on the number of attacks, respectively. The effect of age was significant on the occurrence and number of attacks in men and women, and both the recurrence and progressive clinical course. Conclusion: Younger patients had more occurrences of attacks. Interferon beta-1a (muscle) has a better performance than other drugs in reducing occurrence of attacks. In women, patients taking interferon beta-1b had fewer attacks compared to patients taking interferon beta-1a (muscle). In men, patients taking interferon beta-1a (muscle) had fewer attacks than those taking glatiramer acetate. © 2018, Isfahan University of Medical Sciences(IUMS). All rights reserved

Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment

Multiscale systems biology and systems pharmacology are powerful methodologies that are playing increasingly important roles in understanding the fundamental mechanisms of biological phenomena and in clinical applications. In this review, we summarize the state of the art in the applications of agent-based models (ABM) and hybrid modeling to the tumor immune microenvironment and cancer immune response, including immunotherapy. Heterogeneity is a hallmark of cancer; tumor heterogeneity at the molecular, cellular, and tissue scales is a major determinant of metastasis, drug resistance, and low response rate to molecular targeted therapies and immunotherapies. Agent-based modeling is an effective methodology to obtain and understand quantitative characteristics of these processes and to propose clinical solutions aimed at overcoming the current obstacles in cancer treatment. We review models focusing on intra-tumor heterogeneity, particularly on interactions between cancer cells and stromal cells, including immune cells, the role of tumor-associated vasculature in the immune response, immune-related tumor mechanobiology, and cancer immunotherapy. We discuss the role of digital pathology in parameterizing and validating spatial computational models and potential applications to therapeutics