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Human physiology, hazards and health risks
Published in Stephen Battersby, Clay's Handbook of Environmental Health, 2023
Revati Phalkey, Naima Bradley, Alec Dobney, Virginia Murray, John O’Hagan, Mutahir Ahmad, Darren Addison, Tracy Gooding, Timothy W Gant, Emma L Marczylo, Caryn L Cox
When radon is inhaled, its 3.82 day half-life means that there is a small probability of the atoms decaying whilst in the lungs, and most are simply exhaled. The decay products, however, not only have much shorter half-lives, but their chemically active nature means that they are more readily caught by the mucous membranes that line the airways; those attached to aerosols tend to deposit in the bronchi, the unattached tend to be deposited more deeply in the lung. Once on the mucous membranes, the isotopes of polonium, bismuth and lead decay radioactively before the body’s clearance mechanisms can remove them (to the mouth, nose or GI tract). The range of alpha particles in tissue is particularly important, as it corresponds to the distance from the surface of the mucous membrane to the basal cells that line the airways. Radiation damage to the DNA in the cell nucleus risks mutations that can lead to cancer.
Genome Editing and Gene Therapies: Complex and Expensive Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
In October 2012, The Nobel Assembly at the Swedish Karolinska Institute decided to award The Nobel Prize in Physiology or Medicine 2012 jointly to John B. Gurdon, who discovered already in 1962 that the differentiation of cells is reversible (Gurdon, 1962; 2006; Blau, 2014), and to Shinya Yamanaka, who found in 2006 that mature cells can be reprogrammed to become pluripotent. These findings demonstrated that cell specialization is not accompanied by a loss or permanent silencing of genes. In other words, nuclei from somatic cells can be induced to express genes characteristic of embryonic stem cells. These iPSCs meanwhile derived from many somatic cell types including a variety of animal species are, similar to ESCs, capable of in vitro proliferation thereby retaining the ability to differentiate into various cell types. Experiments with easily accessible human iPSCs, among them patient-specific PSCs, reduce—but not eliminate—the ethical issues linked to human ESCs due to their embryonic origin. Hence, iPSCs as an alternative to animal models can be used to produce all types of patient-specific somatic cells (that is they all contain the genetic information of the patient with all genetic alterations causing the particular disease) which are of high value for disease modeling, toxicity testing, drug screening as well as transplantation therapies (e.g., Yu and Thomson, 2014) because complications that were anticipated from immune rejections might be avoided.
Magnetic Resonance Imaging
Published in Shoogo Ueno, Bioimaging, 2020
Magnetic resonance imaging (MRI) is a technique to obtain images based on nuclear magnetic resonance (NMR) signals generated by nuclei under a strong magnetic field. The MRI technique was demonstrated by Paul Lauterbur in 1973 [1]. The method later progressed through the development of magnets that stably generate strong magnetic fields, developments of diverse imaging techniques and increases in scan speed, the application of diagnosing various diseases, and the development of image processing methods, until it became an essential technology for imaging diagnosis. Features of MRI that distinguish it from other diagnostic imaging methods include the high contrast between soft tissues and the acquisition of functional information such as metabolic processes and brain activity in addition to morphological information. Furthermore, it involves no radiation exposure and is noninvasive. This chapter introduces the basic principles of MRI and the mechanism of imaging methods such as functional MRI and diffusion MRI.
Nonviral gene delivery using PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from human papillomavirus type 11 E2 protein
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Jeil Lee, Yong-Eun Kwon, Jaegi Kim, Dong Woon Kim, Hwanuk Guim, Jehyeong Yeon, Jin-Cheol Kim, Joon Sig Choi
Therapeutic genes must be delivered to the nuclear region for successful gene therapy. However, nonviral vectors have difficulties in selectively delivering DNA molecules into the nuclear region, limiting their application in genetic medicine. Nonviral gene delivery is inhibited by membranous barriers; one of these, the nuclear envelope, consists of two lipid bilayer membranes and a nuclear pore complex (NPC), limiting the entry of molecules larger than 9 nm. NLS is a tag sequence that enables the transport of proteins from the cytoplasm to the nuclear region and permits the active transport of molecules up to 39 nm [29]. Since the size of the cationic polymer/pCN-Luci polyplexes was too large to directly penetrate the NPC pores, we hypothesized that PAMAM derivatives conjugated with NLS peptides/pCN-Luci polyplexes would be localized in the perinuclear region because of their size, and subsequently delivered to the nuclear region when the nuclear envelope disappears during mitosis. In our previous study, polyplexes of PAMAM derivatives conjugated with NLS peptides and pCN-Luci showed high transfection efficiency and perinuclear localization. A series of experiments and previous findings indicate that each factor, such as enhanced cellular uptake and proton-buffering capacity, affects the transfection efficiency of PAMAM derivatives modified with NLS peptides, which showed a lower proton-buffering capacity than PEI 25 kDa [17–19]. If proton-buffering capacity was the main reason for the increased transfection efficiency, PAMAM derivatives modified with NLS peptides should have a buffering capacity similar to that of PEI (25 kDa). Therefore, the improved transfection efficiency of RKRAR- and RKRARH-PAMAM G2 may be a product of the combined effects of these three factors.
Tweedie hidden Markov random field and the expectation-method of moments and maximisation algorithm for brain MR image segmentation
Published in Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization, 2023
Mouna Zitouni, Masmoudi Afif, Mourad Zribi
Medical image processing is one of the most crucial subfields in not only statistics, but also engineering and radiology. It permeates several domains such as image segmentation, and image registration. Its significance refers to its ability to extract information about the human body, and more specifically about tissue characterisation,organs, anatomic structures, lesions and tumours. This information helps doctors delineate and track the progress of diseases. Basically, there are three major types of imaging commonly used for the diagnosis of brain tumours (Anne-Sophie 2003; Atam 2010). The Computed Tomography is a diagnostic imaging test used to create detailed images of internal organs, bones, soft tissue and blood vessels. The scintigraphic imaging is one of the methods used in order to study the transmission, the metabolism and duration life of a substance in the body as well as the functioning of the body. It is an exploration technique that exploits the radioactive properties of the matter. It rests on injecting to the patient a certain dose of radioactive product. The injected products differ according to the pathology and the organ concerned. The scintigraphic image is then a representation of the Radiation emitted by the injected radioactive elements. Finally, the Magnetic Resonance Imaging (MRI) is a tomographic imaging technique that produces images of internal physical and chemical characteristics of an object from externally measured Nuclear Magnetic Resonance (NMR) signals. It is the modality of choice for evaluating patients who have symptoms and signs suggesting a brain tumour (complex structure). World health organisation (WHO) classifies brain tumours into 4 grades. Grade I and Grade II are benign brain tumours. Grade III and Grade IV are malignant tumours. The major tumours types are meningiomas, glioblastoma and medulloblastoma.
Human reliability assessment in a 99Mo/99mTc generator production facility using the standardized plant analysis risk-human (SPAR-H) technique
Published in International Journal of Occupational Safety and Ergonomics, 2019
Meysam Eyvazlou, Ali Dadashpour Ahangar, Azin Rahimi, Mohammad Reza Davarpanah, Seyed Soheil Sayyahi, Mehdi Mohebali
As nuclear medicine is making significant progress around the world, similar progress has been made in Iran within three main areas, including imaging, in vitro and laboratory studies, and therapy [7]. Nuclear medicine plays an important role in the diagnosis and treatment of many diseases. It also provides useful information about the patient's health, which is not easily obtainable by other diagnostic methods [8]. For this purpose a radiopharmaceutical, i.e., a radioactive compound, is used. In nuclear medicine, about 95% of radiopharmaceuticals are used for diagnosis and the remaining 5% are used for treatment. Radiopharmaceuticals consist of two parts, a radionuclide and a pharmaceutical, and their advantages depend on their specifications. Many radionuclides have been produced in reactors and linear accelerators [9]. 99mTc radiopharmaceuticals are mostly used in nuclear medicine for diagnostic purposes. Radionuclide generators have an important role in the development and usability of these tracers. Irradiation caused by radiopharmaceutical production has turned into a dangerous and complicated process. Exposure to radiation and contamination caused by handling radioactive substances could damage workers’ health in these facilities [10]. With regard to the consequences of human error in the radiopharmaceutical production process that causes radiation accidents for the exposed workers as well as the increasing need to use 99mTc in the nuclear medicine centers, this study aimed to analyze human error and to provide control measures in a radiopharmaceutical manufacturing facility in Iran. In addition, it is noteworthy that few studies have so far been conducted on the human reliability assessment for these facilities in Iran. To achieve this goal, the SPAR-H technique was used to estimate the human error probability (HEP). This technique is a systematic method for quantification of the human role in the occurrence of errors [2].