Rare Case of Hodgkin Lymphoma Transformation into Diffuse Large B-Cell Lymphoma with Atypical Spread Epidurally, Intradurally and Intramedullary : A Case Report

Publisher Copyright: © Am J Case Rep.BACKGROUND Hodgkin lymphoma (HL) transformation into diffuse large B-cell lymphoma (DLBCL) is uncommon, and scant information has been published on transformed high-grade lymphomas. Therefore, it is important to present and discuss cases of lymphoma transformation to make new information on disease progression, diagnosis, and treatment more readily available. In this paper, we present a case of HL transformation into DLBCL with atypical dissemination. CASE REPORT A 39-year-old woman presented with severe hip pain. A computed tomography (CT) scan was performed, which showed massive pathological retroperitoneal and pelvic lymphadenopathy. The lymph nodes were biopsied and revealed HL. The patient then underwent 7 cycles of ABVD therapy; however, clinical concern was raised for persistent disease due to the poor response to therapy. A vertebral body biopsy was performed to clarify the diagnosis, and histological analysis revealed DLBCL. Therefore, specific chemotherapy with the R-CHOP scheme was begun; the patient received 8 cycles of rituximab and residual lymphoma tissue irradiation. Two months later, magnetic resonance imaging later demonstrated radiological disease progression with multiple widespread metastases in the spinal vertebrae as well as prevertebral, epidural, intradural, and intramedullary metastatic spread. The patient underwent intrathecal chemotherapy and radiation therapy, after which, full metabolic remission was observed on PET/CT. CONCLUSIONS Vigilance should be maintained for patients with poor response to HL treatment owing to the possible transformation into DLBCL. However, even in such cases, full metabolic remission can be achieved with appropriate treatment.publishersversionPeer reviewe

Sustainable architecture: trends in higher professional architectures’ education

In the article we tried to investigate theoretical ideas concerning actual students’ reasons for education in the field of architecture in frame of the second level of higher professional education system. We present the results of survey that we conducted last year. We collected data about students’ reasons to enrol for architectures’ and others master programmes and their expectations of programmes’ content, programmes’ volume, curriculum structure, placement periods. We analysed the teaching methods, structure and trends in architecture’s master programmes that was legally introduced by government standards. As a result, we concluded that the changes of education standards mostly meet expectations of master programmes contenders. However, the contenders will succeed in higher school only if their motivation is enough strong and appropriate

An efficient platform for astrocyte differentiation from human induced pluripotent stem cells

Summary: Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. : Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis. Keywords: human induced pluripotent stem cell, iPSC, astrocyt

Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2

Alzheimer\u27s disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. More than 200 pathogenic mutations have been identified in amyloid-β precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Additionally, common and rare variants occur within APP, PSEN1, and PSEN2 that may be risk factors, protective factors, or benign, non-pathogenic polymorphisms. Yet, to date, no single study has carefully examined the effect of all of the variants of unknown significance reported in APP, PSEN1 and PSEN2 on Aβ isoform levels in vitro. In this study, we analyzed Aβ isoform levels by ELISA in a cell-based system in which each reported pathogenic and risk variant in APP, PSEN1, and PSEN2 was expressed individually. In order to classify variants for which limited family history data is available, we have implemented an algorithm for determining pathogenicity using available information from multiple domains, including genetic, bioinformatic, and in vitro analyses. We identified 90 variants of unknown significance and classified 19 as likely pathogenic mutations. We also propose that five variants are possibly protective. In defining a subset of these variants as pathogenic, individuals from these families may eligible to enroll in observational studies and clinical trials

The Genre of the Soviet Poster in the Fine Arts of 1917–1922

Статья посвящена советскому плакату первой пятилетки Советской России – 1917–1922 гг. Плакат в рассматриваемый исследованием период выступает одним из главных жанров изобразительного искусства, именно он становится самым реагирующим на актуальные исторические события и перемены, а также принимает актуальные вызовы времени. В этом жанре активно ведется поиск адекватных форм выражения актуальных общественно-политических идей и внедрение в поле общественного сознания ценностей нового строящегося мира. Статья рассматривает как феномены плакатного искусства с 1917 по 1922 г. в целом, так и представляет анализ отдельных репрезентантов плаката этого времени. Методологической основой исследования выступает теория изобразительного искусства В. И. Жуковского и философско-искусствоведческий анализ. В качестве анализируемых репрезентантов авторами выбраны плакаты А. П. Апсита «На коня, пролетарий!» (1918 г.) и Д. С. Моора «Враг у ворот! Он несет рабство, голод и смерть!» (1919 г.). Исследование плакатов демонстрирует специфику сложения актуальных образов этого периода и своеобразие художественных идей данных произведенийThe article is devoted to the Soviet poster of the first five-year plan of Soviet Russia – 1917–1922. The poster in the period under consideration is one of the main genres of fine art, it is he who becomes the most responsive to current historical events and changes, and also accepts the actual challenges of the time. In this genre, an active search is being made for adequate forms of expression of current socio-political ideas and the introduction of the values of the new world under construction into the field of public consciousness. The article considers both the phenomena of poster art from 1917 to 1922 as a whole and presents an analysis of individual representatives of the poster of this time. The methodological basis of the study is the theory of fine arts by V. I. Zhukovsky and philosophical and art history analysis. The posters of A. P. Apsita “On the horse, proletarian!” (1918) and D. S. Moora “The enemy is at the gates! He brings slavery, hunger and death!” (1919). The study of posters demonstrates the specifics of the composition of actual images of this period and the originality of the artistic ideas of these work

The Transformation of Architectural Styles in Soviet Art 1917–1922

Статья посвящена изменениям в архитектуре первой пятилетки Советской России – 1917–1922 годов. Это время глобальной реорганизации общества и образа жизни, кардинальных изменений в общественно-политических взглядах, трансляции новых ценностей и идеалов силами искусства. Градостроительство и архитектура одними из первых оказались в поле преобразований, поскольку вопрос строительства нового мира напрямую касался архитектурной формы и городского планирования. Архитектура выступает символическим воплощением этого нового мира и общества. Принципы социалистического строительства включали в себя особенности организации городской жизни, пространства города. В статье рассмотрены проекты А. В. Щусева («Новая Москва», 1918–1923 гг.) и С. С. Шестакова («Большая Москва», 1921–1925 гг.). В качестве репрезентативного типа нового общественного сооружения рассмотрен «дворец» как средоточие культурной, общественной и политической жизни трудящихся. Статья фиксирует ведущее положение конструктивизма как появившейся архитектурной традиции, и основным содержанием выступает анализ проекта «Памятника III Интернационалу» В. Е. Татлина как образа-символа нового строя и общего движения в построении коммунизмаThe article is devoted to changes in the architecture of the first five-year plan of Soviet Russia, 1917–1922. This is a time of global reorganization of society and lifestyle, fundamental changes in socio-political views, the transmission of new values and ideals by the forces of art. Urban planning and architecture were among the first to be in the field of transformation, since the issue of building a new world directly concerned the architectural form and urban planning. Architecture is a symbolic embodiment of this new world and society. The principles of socialist construction included the features of the organization of urban life, the space of the city. The article considers the projects of A. V. Shchusev (“New Moscow”, 1918–1923) and S. S. Shestakova (“Greater Moscow”, 1921–1925). As a representative type of a new public building, the “palace” is considered as the center of the cultural, social and political life of the working people. The article fixes the leading position of constructivism as an emerging architectural tradition, and the main content is the analysis of the project “Monument to the III International” by V. E. Tatlin as an image-symbol of the new system and the general movement in building communis

The Image of Artificial Intelligence in Cinema: Transformations in the 1980s‑2010s

Статья посвящена актуальной теме образа искусственного интеллекта в кинематографе как осмысления отношения к внедрению высоких технологий в жизнь человека и как средства осмысления человеком не только искусственного интеллекта, но и самого себя. В качестве репрезентативных этапов авторами выбраны исторические периоды 1980–1990-х, 2000-х и 2010-х гг. Методологической основой исследования выступил и философско-искусствоведческий и сравнительный анализ кинофильмов. В качестве материала для исследования выбраны популярные в свое время и ставшие классикой киноленты: «Бегущий по лезвию» (Р. Скотт, 1981 г.), «Призрак в доспехах» (М. Осии, 1995 г.), «Искусственный разум» (С. Спилберг, 2001), «Прометей» (Р. Скотт, 2012), «Чужой: Завет» (Р. Скотт, 2017). Исследование показывает, что основными вопросами, которые поднимает кинематограф 1980–2010-х гг. в связи с образом искусственного интеллекта, можно назвать вопросы взаимодействия человека и созданного им андроида, характера их отношений, возможного равенства. Кинорепрезентанты демонстрируют актуальность тем степени признания человечности антропоморфного робота, его самосознания, статуса в человеческом обществе, этики отношений людей и машин. Образ искусственного интеллекта развивается от представлений о нем как о во многом равном человеку к репрезентации его как угрозы для положения человека в миреThe article is devoted to the actual topic of the image of artificial intelligence in cinematography as an understanding of the attitude to the introduction of high technologies in human life and as a means of understanding not only artificial intelligence, but also oneself. The historical periods of the 1980s – 1990s, 2000s and 2010s are chosen as representative stages. The methodological basis of the study was also a philosophical, art history and comparative analysis of films. As a material for the study, films that were popular in their time and became classics were chosen: «Blade Runner» (R. Scott, 1981), «Ghost in the Shell» (M. Oshii, 1995), «Artificial Intelligence» (S. Spielberg, 2001), «Prometheus» (R. Scott, 2012), «Alien: Covenant» (R. Scott, 2017). The study shows that the main questions that the cinema of the 1980s‑2010s raises in connection with the image of artificial intelligence can be called the issues of interaction between a person and the android he created, the nature of their relationship, and possible equality. Film representatives demonstrate the relevance of the degree of recognition of the humanity of an anthropomorphic robot, its self-awareness, status in human society, and the ethics of relations between people and machines. The image of artificial intelligence is developing from ideas about it as in many respects equal to a person to its representation as a threat to the position of a person in the worl

A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function

Age-related macular degeneration risk factors

Ievads. Vecuma makulas deģenerācija (VMD) ir vadošais iemesls neatgriezeniskam redzes zudumam attīstītajās valstīs. Attīstoties eksudatīvai VMD formai un ģeogrāfiskai atrofijai, rodas nopietna redzes pavājināšanās līdz pat redzes zudumam. Sakarā ar to, ka VMD ir neizārstējama slimība ir svarīgi zināt kādi riska faktori veicina šīs slimības parādīšanos un progresiju, lai, pēc iespējas, palēninātu tās attīstību un novērstu sekojošu redzes zudumu. Diplomdarbā tika pētīti iedzimtības un vides riska faktori, kas potenciāli ietekmē vecuma makulas deģenerācijas smaguma formu. Darba mērķis: Izpētīt potenciālo riska faktoru ietekmi uz vecuma makulas deģenerācijas attīstību. Materiāli un metodes. Pētījumā tika iekļauts 51 pacients, kas slimo ar dažādas formas VMD. No pacienta aizpildītās aptaujas tika iegūta informācija par pacienta vecumu, dzimumu, oftalmoloģisko ģimenes anamnēzi, profesiju, smēķēšanas ieradumu, un blakusslimībām. No slimības vēstures iegūti dati par refrakciju un diagnozes uzstādīšanas gadu. Ar optiskās koherentās tomogrāfijas (OCT) izmeklēšanas metodi un fundus kameru tika noteikta pacienta VMD forma uz doto brīdi, kā arī ar fundus kameru tika fotografēta acs varavīksnene un konstatēta tās pigmenta krāsa. Dati tika analizēti ar SPSS 22,0 versijas programmu. Rezultāti. Vidējais pacientu vecums ir 74,7 ± 9,8 gadi. Pētījumā piedalījās 15 vīrieši (29,4 %) un 36 sievietes (70,6 %). 18 % pacientu ir sausa VMD forma, 47 % - mitra un 35 % pacientu atrofiska VMD forma. Starp varavīksnenes pigmenta krāsu un VMD formu Pīrsona hī kvadrāta testā statistiski ticama asociācija netiek konstatēta (Pχ = 0,42), bet apskatot datus procentuālā sadalījumā var novērot gaišas varavīksnenes pigmenta krāsas prevalenci visās VMD formās. Starp pārmantotību un VMD formu netiek konstatēta statistiski ticama asociācija (Pχ > 0,05). Starp zilās gaismas ekspozīciju un VMD formu netiek konstatēta statistiski ticama asociācija (Pχ > 0,05). Smēķēšana netiek asociēta ar VMD formu (Pχ > 0,05). Netiek konstatēta asociācija starp cukura diabētu, hipertensiju, koronāru sirds slimību, supraventrikulāru aritmiju un VMD formu (Pχ > 0,05). Pēc iegūtajiem rezultātiem tika konstatēts, ka slimības ilgums statistiski korelē (Pr = 0,03, kas ir 0.05). No statistically significant association (Pχ > 0.05) was found between blue light exposure and AMD form. Smoking is not statistically associated with the AMD form (Pχ > 0.05). No association was found between diabetes mellitus, hypertension, coronary heart disease, supraventricular arrhythmia and AMD (Pχ > 0.05). According to the obtained results, it was found that the duration of the disease statistically correlate (Pr = 0.03, which is < 0.05) with the form of AMD. Conclusions. The duration of illness is statistically significantly correlated with its form. No statistically significant association was found between iris pigment color, heredity, smoking, blue light exposure, coronary heart disease and age-related macular degeneration form

Regulation of amyloid precursor protein processing by serotonin signaling

Alzheimer`s disease (AD) is the most common neurodegenerative disorder in elderly people characterized by significant memory loss, difficulty completing familiar tasks and changes in mood, behavior and personality. Eventually the affected person will be dependent on the caregiver for the daily life activities, considerably increasing the social and economic burden. The pathological hallmarks of AD are aggregation of hyperphosphorylated tau in the neurofibrillary tangles and deposition of Amyloid ß (Aß) peptides in the amyloid plaques. Aß is generated by the sequential cleavage of the amyloid precursor protein (APP) by ß- and gamma-secretases. On the other hand APP can also be cleaved within the Aß sequence by alfa-secretase, preventing Aß formation and leading to the soluble APPalfa (sAPPalfa) secretion. Activation of alfa-secretase activity could be beneficial for AD and is therefore considered as a therapeutic target.Regulation of alfa-secretase activity can occur through activation of signaling cascades of kinases and second messengers by the G protein-coupled receptors (GPCR), such as the muscarinic, glutamatergic and serotonergic receptors. The G protein-coupled 5-hydroxytryptamine 4 receptor (5-HT4) is gaining considerable interest as a modulator of the alfa-secretase activity due to its role in learning and memory and regulation of APP processing. Activation of the 5-HT4 receptor leads to an increase in the neuronal activity in the hippocampal CA1 region, and this effect persists in a transgenic mouse model of AD, suggesting that 5-HT4 receptor-mediated signaling remains functional under these pathological conditions. On the other hand, agonist stimulation of the 5-HT4 receptors results in increased sAPPalfa secretion with concomitant decrease in Aß peptide level in the primary neuronal cultures and alleviation of amyloid plaque load in AD mouse models, which is beneficial for learning and memory when tested in behavioral paradigms of the cognitive impairment.Despite numerous reports on the 5-HT4 receptor function in learning and memory, the downstream signaling pathways responsible for the 5-HT4 receptor-mediated effect remain poorly understood. Recent evidence suggests that the 5-HT4 receptors physically interact with a disintegrin and metalloproteinase ADAM10, a major constitutive APP alfa-secretase, but the identity of the 5-HT4 receptor-induced alfa-secretase activity remains unknown. To identify the inducible alfa-secretase and to elucidate the signaling pathway leading to the 5-HT4 receptor-induced alfa-secretase activity we used human SH-SY5Y neuroblastoma cells. Proteins contributing to the 5-HT4 receptor-induced sAPPalfa secretion were identified with chemical inhibition of putative signaling molecules, second messenger assays, overexpression of mutant proteins and RNAi knock-down.Our data indicate that G proteins, Src, phospholipase C (PLC), inositol polyphosphates and casein kinase 2 (CK2) are essential for alfa-secretase activation following the 5-HT4 receptor stimulation. Downstream effect on the sAPPalfa secretion is mediated by Galfa and Gßgamma signaling and by Src non-receptor tyrosine kinase-dependent activation of PLC. ß-arrestin signaling had no effect on the sAPPalfa secretion. In contrast to previous publications, we find that adenylyl cyclase, cAMP, calcium and protein kinase C signaling do not contribute to the 5-HT4 receptor-stimulated APP shedding. Finally, inositol triphosphate conversion to inositol polyphosphates by multikinases results in activation of CK2. RNAi-mediated downregulation of ADAM9, 10, 17 and MMP9 suggests that yet a different metalloproteinase, contributes to the 5-HT4 receptor-induced sAPPalfa release. In conclusion, we provide novel insight in the signaling molecules responsible for the 5-HT4 receptor-stimulated sAPPalfa induction. This knowledge will allow for a better understanding of potential risks that could be involved when modifying signaling pathways leading to increased alfa-secretase activity.status: publishe