109 research outputs found
Дозы облучения персонала и населения при нормальной эксплуатации пунктов захоронения радиоактивных отходов
This paper focuses on occupational and public exposure during operation of disposal facilities receiving liquid and solid radioactive waste of various classes and provides a comparative analysis of the relevant doses: actual and calculated at the design stage. Occupational and public exposure study presented in this paper covers normal operations of a radioactive waste disposal facility receiving waste. Results: Analysis of individual and collective occupational doses was performed based on data collected during operation of near-surface disposal facilities for short-lived intermediate-, lowand very low-level waste in France, as well as nearsurface disposal facilities for long-lived waste in Russia. Further analysis of occupational and public doses calculated at the design stage was completed covering a near-surface disposal facility in Belgium and deep disposal facilities in the United Kingdom and the Nizhne-Kansk rock massive (Russia). The results show that engineering and technical solutions enable almost complete elimination of internal occupational exposure, whereas external exposure doses would fall within the range of values typical for a basic nuclear facility. Conclusion: radioactive waste disposal facilities being developed, constructed and operated meet the safety requirements effective in the Russian Federation and consistent with relevant international recommendations. It has been found that individual occupational exposure doses commensurate with those received by personnel of similar facilities abroad. Furthermore, according to the forecasts, mean individual doses for personnel during radioactive waste disposal would be an order of magnitude lower than the dose limit of 20 mSv/year. As for the public exposure, during normal operation, potential impact is virtually impossible by delaminating boundaries of a nuclear facility sanitary protection zone inside which the disposal facility is located and can be solely attributed to the use of public roads during radioactive waste transportation to the disposal facility site. Цель работы – сравнительный анализ фактических и оцениваемых на этапе проектирования доз облучения персонала и населения при захоронении жидких радиоактивных отходов и твердых радиоактивных отходов различных классов. В рамках настоящей статьи рассматривается вариант облучения персонала и населения при нормальной эксплуатации пункта захоронения радиоактивных отходов в режиме размещения отходов. Результаты: выполнен анализ индивидуальных и коллективных доз облучения персонала при приповерхностном захоронении короткоживущих среднеактивных, низкоактивных и очень низкоактивных радиоактивных отходов во Франции, а также при приповерхностном захоронении долгоживущих радиоактивных отходов в России. Проведен анализ проектных оценок доз облучения персонала и населения для объекта приповерхностной изоляции радиоактивных отходов, планируемого к сооружению в Бельгии, а также проектируемых объектов глубинного захоронения в Великобритании и Нижнеканском массиве (Российская Федерация). Техническими и технологическими решениями удается практически полностью исключить внутреннее облучение персонала, а дозы внешнего облучения ограничить диапазоном, характерным и для базовых ядерных технологий. Заключение: планируемые к сооружению, сооружаемые и эксплуатируемые пункты захоронения удаляемых радиоактивных отходов соответствуют действующим в России требованиям безопасности, согласующимся с международными рекомендациями. Оценено, что индивидуальные дозы облучения персонала сопоставимы с данными контроля персонала аналогичных объектов в других странах. Средние индивидуальные дозы облучения персонала при захоронении радиоактивных отходов прогнозируются на порядок ниже установленного предела дозы – 20 мЗв/год. Воздействие на население при нормальной эксплуатации практически исключено установлением санитарно-защитной зоны объекта использования атомной энергии, на которой размещена установка по захоронению отходов, и возможно только при транспортировке радиоактивных отходов по дорогам общего пользования к месту расположения пункта захоронения радиоактивных отходов.
Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages
This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments
Sexuality and Body Image After Uterine Artery Embolization and Hysterectomy in the Treatment of Uterine Fibroids: A Randomized Comparison
In this paper the effect of uterine artery embolization (UAE) on sexual functioning and body image is investigated in a randomized comparison to hysterectomy for symptomatic uterine fibroids. The EMbolization versus hysterectoMY (EMMY) trial is a randomized controlled study, conducted at 28 Dutch hospitals. Patients were allocated hysterectomy (n = 89) or UAE (n = 88). Two validated questionnaires (the Sexual Activity Questionnaire [SAQ] and the Body Image Scale [BIS]) were completed by all patients at baseline, 6 weeks, and 6, 12, 18, and 24 months after treatment. Repeated measurements on SAQ scores revealed no differences between the groups. There was a trend toward improved sexual function in both groups at 2 years, although this failed to reach statistical significance except for the dimensions discomfort and habit in the UAE arm. Overall quality of sexual life deteriorated in a minority of cases at all time points, with no significant differences between the groups (at 24 months: UAE, 29.3%, versus hysterectomy, 23.5%; p = 0.32). At 24 months the BIS score had improved in both groups compared to baseline, but the change was only significant in the UAE group (p = 0.009). In conclusion, at 24 months no differences in sexuality and body image were observed between the UAE and the hysterectomy group. On average, both after UAE and hysterectomy sexual functioning and body image scores improved, but significantly so only after UAE
Neisseria meningitidis Differentially Controls Host Cell Motility through PilC1 and PilC2 Components of Type IV Pili
Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P) that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC2) brings a new model to light for the analysis of the interplay between pathogenic bacteria and human host cells
Adjuvant electrochemotherapy in veterinary patients: a model for the planning of future therapies in humans
The treatment of soft tissue tumors needs the coordinated adoption of surgery with radiation therapy and eventually, chemotherapy. The radiation therapy (delivered with a linear accelerator) can be preoperative, intraoperative, or postoperative. In selected patients adjuvant brachytherapy can be adopted. The goal of these associations is to achieve tumor control while maximally preserving the normal tissues from side effects. Unfortunately, the occurrence of local and distant complications is still elevated. Electrochemotherapy is a novel technique that combines the administration of anticancer agents to the application of permeabilizing pulses in order to increase the uptake of antitumor molecules. While its use in humans is still confined to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, in veterinary oncology this approach is rapidly becoming a primary treatment. This review summarizes the recent progresses in preclinical oncology and their possible transfer to humans
Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier
Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens
Stromal IFN-γR-Signaling Modulates Goblet Cell Function During Salmonella Typhimurium Infection
Enteropathogenic bacteria are a frequent cause of diarrhea worldwide. The mucosal defenses against infection are not completely understood. We have used the streptomycin mouse model for Salmonella Typhimurium diarrhea to analyze the role of interferon gamma receptor (IFN-γR)-signaling in mucosal defense. IFN-γ is known to contribute to acute S. Typhimurium diarrhea. We have compared the acute mucosal inflammation in IFN-γR-/- mice and wild type animals. IFN-γR-/- mice harbored increased pathogen loads in the mucosal epithelium and the lamina propria. Surprisingly, the epithelium of the IFN-γR-/- mice did not show the dramatic “loss” of mucus-filled goblet cell vacuoles, a hallmark of the wild type mucosal infection. Using bone marrow chimeric mice we established that IFN-γR-signaling in stromal cells (e.g. goblet cells, enterocytes) controlled mucus excretion/vacuole loss by goblet cells. In contrast, IFN-γR-signaling in bone marrow-derived cells (e.g. macrophages, DCs, PMNs) was required for restricting pathogen growth in the gut tissue. Thus IFN-γR-signaling influences different mucosal responses to infection, including not only pathogen restriction in the lamina propria, but, as shown here, also goblet cell function
Pathogenic Neisseria Hitchhike on the Uropod of Human Neutrophils
Polymorphonuclear neutrophils (PMNs) are important components of the human innate immune system and are rapidly recruited at the site of bacterial infection. Despite the effective phagocytic activity of PMNs, Neisseria gonorrhoeae infections are characterized by high survival within PMNs. We reveal a novel type IV pilus-mediated adherence of pathogenic Neisseria to the uropod (the rear) of polarized PMNs. The direct pilus-uropod interaction was visualized by scanning electron microscopy and total internal reflection fluorescence (TIRF) microscopy. We showed that N. meningitidis adhesion to the PMN uropod depended on both pilus-associated proteins PilC1 and PilC2, while N. gonorrhoeae adhesion did not. Bacterial adhesion elicited accumulation of the complement regulator CD46, but not I-domain-containing integrins, beneath the adherent bacterial microcolony. Electrographs and live-cell imaging of PMNs suggested that bacterial adherence to the uropod is followed by internalization into PMNs via the uropod. We also present data showing that pathogenic Neisseria can hitchhike on PMNs to hide from their phagocytic activity as well as to facilitate the spread of the pathogen through the epithelial cell layer
Listeria pathogenesis and molecular virulence determinants
The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research
Neisseria meningitidiselicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model
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