Genetics Of Gluten Intolerance

Celiac disease, or extreme gluten intolerance, is an autoimmune disease that primarily causes damage to the small intestine. It is caused by dietary intake of gluten in genetically predisposed individuals. The presentation of celiac disease consists of digestive tract symptoms, mainly diarrhea and subsequent weight loss. Other related symptoms and findings are iron deficiency anemia, decreased bone density, and some nonspecific neurological symptoms.In the recent past, the diagnosis of celiac disease was made based on specific serological tests, small intestinal mucosa biopsy results, and fading away of symptoms after gluten-free diet is applied.After the identification of the disease-specific genes HLA-DQ2 and DQ8, genetic testing was considered the gold standard for the diagnosis of celiac disease, because the presence of a specific genotype is a prerequisite for the development of this disease. Risk variants of HLA-DQ2 and DQ8 are found in about 30% of the general European population. Determining the genetic status allows adequate subsequent clinical decisions. The lack of genetic variants predisposing to celiac disease leads to the exclusion of the diagnosis, while the detection of high-risk variant(s) in an individual prompts additional diagnostic steps through a number of serological and invasive tests. The introduction of genetic analysis has led to a significant reduction in the number of invasive intestinal tests (biopsies).The purpose of this article is to present the current practical approach in the diagnosis of celiac disease, which includes mandatory genetic analysis, and to explain the nature of this autoimmune disease from a genetic point of view

Variational problem for hydrogenerator thrust bearing

Reversible and irreversible heavy loaded thrust bearings of a hydrogenerator are investigated. The problem of oil wedge microgeometry profiling for load capacity optimization is considered. The analysis is based on optimization methods using variational calculus. The results of oil wedge microgeometry optimization for reversible and irreversible thrust bearings are presented

Embodied learning of the German language: teaching methodology for translators and interpreters

Las Ciencias Cognitivas experimentales muestran importantes progresos en cuanto al funcionamiento de los mecanismos de la adquisición de conocimiento y de la memoria. Esos avances deben ser considerados en la carrera de Traducción e Interpretación, ya que la profesión de traductor o intérprete no solo requiere una buena fluidez lingüística, sino también competencias cognitivas específicas muy desarrolladas. Así, numerosos estudios neuro y psicolingüísticos demuestran que las habilidades de la memoria de trabajo y del control ejecutivo interlingüístico, tan imprescindibles para la labor de traducción/interpretación que comprende el balanceo entre dos lenguas, son susceptibles a su entrenamiento mediante prácticas tempranas. Igualmente, existen progresos significativos en el conocimiento sobre otras competencias necesarias para esta labor, como pueden ser la fluidez conceptual, la competencia metafórica o la práctica de discurso en público, entre otras. El presente trabajo describe una experiencia de la didáctica del alemán para futuros traductores o intérpretes que integra los avances de las Ciencias Cognitivas experimentales. Se trata del entrenamiento de las competencias traductoras desde la fase inicial del aprendizaje del alemán, lo que convierte los estudios de Traducción e Interpretación en una experiencia empírica y corporeizada motivadora tanto para los alumnos como para los docentes.Experimental Cognitive Sciences show important progress in terms of the functioning of the knowledge acquisition and memory mechanisms. These advances must be considered in the Translation and Interpreting career, since the profession of translator or interpreter not only requires good linguistic fluency, but also highly developed specific cognitive skills. Thus, numerous neuro and psycholinguistic studies show that the skills of working memory and interlinguistic executive control, so essential for the work of translation/interpretation that includes balancing between two languages, are susceptible to their training through early practices. Likewise, there are significant advances in knowledge about other skills necessary for this task, such as conceptual fluency, metaphorical competence or the practice of public speaking, among others. The present work describes the German teaching experience for future translators or interpreters that integrates the last experimental Cognitive Sciences advances. The present study is about the translation skills training from the initial phase of learning German, which turns Translation and Interpretation studies into an empirical and embodied experience that is motivating for both students and teachers

Genetic polymorphisms predisposing to common cardiovascular diseases

Cardiovascular disease (CVD) is a major health problem worldwide and is a leading cause of disability and mortality. They include coronary heart disease, cerebrovascular disease, peripheral vascular disease and arterial atherosclerosis. In the most cases, CVDs are polygenic multifactorial socially significant diseases and result from the impact of predisposing environmental factors, mainly related to unhealthy lifestyles, acting on a sensitive genetic terrain. This is due to specific genetic variants that control the regulation of the renin-angiotensin-aldosterone system (RAAS), lipid metabolism, caffeine metabolism, omega-3 fatty acids, homocysteine, etc. Such common genetic variants are designated as SNPs (Single Nucleotide Polymorphisms). The more predisposing variants an individual carries, the more pronounced the genetic risk of developing CVD. Such genetic variations are: variations in the ACE (insertion/deletion—I/D) and AGT (C-344T) genes of the RAAS; variations in the ApoE gene (Apo E2, E3 and E4) associated with cholesterol metabolism, genetic polymorphism C3175G in the gene encoding apolipoprotein C—APOC3; CETP gene with polymorphism rs708272, 279 G>A, associated with high-density cholesterol metabolism; lipoprotein lipase (LPL) gene and polymorphism 1595C>G (Ser447X); a polymorphism in CYP1A2 associated with caffeine sensitivity; polymorphism rs174537 G>T in FADS1 involved in polyunsaturated fatty acid metabolism, and polymorphisms in MTHFR (677 C>T and 1298 A>C) associated with homocysteine metabolism

Perspectives For Target Therapy In The Treatment Of Malignant Neoplasms Of The Urinary Bladder

Етиологията, патогенезата и лечението на злокачествените новообразувания на пикочния мехур все още пораждат редица въпроси. Установени са биомаркери, показващи разлики в молекулния образ на инвазивния и неинвазивния уроепителен карцином, които са част от факторите, отговорни за големите вариации в лечението дори и при тумори с еднакъв хистологичен резултат. В момента стандартно прилаганата системна терапия включва различни цитотоксични химиотерапевтични схеми и се основава главно на хистологичната оценка и стадирането на тумора. От май 2016 г. за първи път се разреши прилагането на прицелна терапия при лечение на онкологични зболявания на пикочен мехур. Прицелната терапия се използва за спиране на растежа и разпространението на раковите клетки, посредством потискане на активирани сигнални пътища - най-често на фибробластния, епидермалния и ендотелния растежен фактор. Изборът на „правилното` лекарство се базира до голяма степен върху молекулно-генетичната диагноза на тумора и наличие на специфични биомаркери, показващи възможността за прилагане на едно или друго лекарство.През последните години е постигнат значителен напредък в ерата на молекулната диагностика и прицелната терапия, което неминуемо води до удължаване на преживяемостта на онкопоциентите и подобряване качеството им на живот. В тази статия ние разглеждаме потенциалните и съществуващите възможности за приложение на прецизирана терапия при пациенти с уроепителни тумори.The etiology, pathogenesis and treatment of malignant neoplasms of the bladder still address a number of issues. Several biomarkers have been identified showing differences in the molecular image of invasive and non-invasive uroepithelial carcinoma. These biomarkers are part of the factors responsible for the large variation in treatment even in tumors with the same histological diagnosis. Currently, standard systemic therapy includes various cytotoxic chemotherapy regimens and is based mainly on histological evaluation and tumor progression. Since May 2016, target therapy has been approved for the first time in the treatment of oncological bladder disease. Target therapy is used to stop the growth and spread of cancer cells by suppressing activated signaling pathways - most often fibroblast, epidermal and endothelial growth factor pathways. The choice of „ the right` drug is largely based on the molecular genetic diagnosis of the tumor and the presence of specific biomarkers indicating the applicability of one or another drug.Significant progress has been made in the era of molecular diagnosis and target therapy, which leads to prolonged survival and improved quality of life of oncology patients. In this article, we examine the potential and existing options for the use of precision therapy in patients with uroeptithelial tumors

Optimum design of hydrodynamic thrust bearings with rayleigh's pocket profiles

Optimum design problem for hydrodynamic self-aligning acting thrust bearings was considered. Based on results for rectangular region the problem for sector region was solved. As an objective function, the maximum of pressure integral over the lubricant layer surface was used and five geometrical parameters described Rayleigh's pocket shape were used as optimization variables during optimization procedure. The bearing pressure distribution was determined on the basis of the Navier-Stokes equations using the ANSYS / CFX software. Numerically the optimization problem was solved using three different methods: IOSO, SIMPLEX and pilOPT+AFilter SQP realized in two commercial optimization software IOSO and modeFRONTIER. The aim of this investigation was designing the technologically advanced profiles of thrust bearing sector microgeometry ensuring the maximum load capacity

Endometriosis - Review Of Current Therapeutic Aproaches For Disease Control

Ендометриозата е хронично естроген-зависимо заболяване, което се характеризира с развитие на ендометриална тъкан извън маточната кухина. В световен мащаб засяга около 10% от жените. Заболяването може да причини дисменорея, хронична тазова болка, диспареуния и инфертилитет. Медикаментозното лечение играе ключова роля в контрола на заболяването. В повечето случаи е наложително лекарствената терапия да бъде комбинирана с хирургична, за да бъде постигнато пълно излекуване. Подходът при избор на подходящо медикаментозно лечение трябва да бъде индивидуализиран, като бъде съобразен с тежестта на ендометриозата, ефикасността на лекарството, страничните му ефекти, желанието на пациентката, възрастта ѝ и репродуктивните ѝ планове. Голяма част от използваните днес лекарства за лечение на ендометриоза целят потискане на овариалната функция. Най-често прилаганите и показващи най-добри резултати са комбинираните орални контрацептиви, аналозите на гонадотропин-освобождаващия хормон и прогестините. Освен тези утвърдени терапии, съвременното лечение включва и нови хормонално и нехормонално-базирани терапевтични подходи, които модулират различни патогенетични механизми. В този обзор ще бъдат разгледани настоящите терапевтични опции - както класическите, така и по-новите, все още неодобрени медикаменти за лечение на ендометриоза.Endometriosis is an estrogen-dependent chronic disease characterized by the presence of endometrial tissue outside the uterine cavity. Globally, it affects about 10% of women worldwide. It causes dysmenorrhea,chronic pelvic pain, dyspareunia, and infertility.Medication treatment plays a key role in disease management. In most cases, medications should be combined with surgery in order to eradicate the disease. The medication treatment should be individualized considering the severity of endometriosis, efficacy of the drug, its side effects, patient`s preferences, age, and reproductive plans. Nowadays, most of the drugs used to treat endometriosis aim to suppress ovarian function. The most widelyused and with the best therapeutic outcomes are the combined oral contraceptives, gonadotropin-releasing hormone agonists, and progestins. In addition to these well-established therapies, new horomonal and non-hormonal therapeutics that modulate various pathogenic pathways are available. We review currently availabletreatment options - the classical ones and the new therapies that are still not approved